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Sample records for mast cell-depleted rats

  1. Pavlovian Conditioning of Rat Mucosal Mast Cells to Secrete Rat Mast Cell Protease II

    NASA Astrophysics Data System (ADS)

    MacQueen, Glenda; Marshall, Jean; Perdue, Mary; Siegel, Shepard; Bienenstock, John

    1989-01-01

    Antigen (egg albumin) injections, which stimulate mucosal mast cells to secrete mediators, were paired with an audiovisual cue. After reexposure to the audiovisual cue, a mediator (rat mast cell protease II) was measured with a sensitive and specific assay. Animals reexposed to only the audiovisual cue released a quantity of protease not significantly different from animals reexposed to both the cue and the antigen; these groups released significantly more protease than animals that had received the cue and antigen in a noncontingent manner. The results support a role for the central nervous system as a functional effector of mast cell function in the allergic state.

  2. Release of mast cell mediators, vasoconstriction and edema in the isolated, perfused head of the rat following intracarotid infusion of neurotensin.

    PubMed

    Rioux, F; Kérouac, R; St-Pierre, S

    1985-03-01

    Intracarotid infusions of neurotensin (NT) into the isolated, perfused head of rats trigger concentration-dependent histamine and 5-hydroxytryptamine (5-HT) release from the perfused organ. The secretory event was accompanied by a concentration-dependent rise in perfusion pressure and facilitation of edema formation. The three NT effects were markedly reduced in heads derived from rats pretreated with high doses of compound 48/80 to produce mast cell depletion. The vasoconstrictor response to NT was greatly attenuated by the 5-HT receptor antagonist methysergide but unaffected by antihistaminic drugs. The results were interpreted as an indication that NT stimulates histamine and 5-HT release from mast cells of the rat perfused head. The results also suggest that the vasoconstrictor response to NT in the rat head is mediated by mast cell 5-HT. The potentiation of edema formation by NT was attributed to the action of mast cell mediators (most likely histamine and 5-HT) released by NT on microvessels.

  3. Vaginal bacterial flora activates rat peritoneal mast cells.

    PubMed

    Brzezińska - Błaszczyk, E.; Wasiela, M.

    2002-01-01

    Sixteen strains of physiological and pathological vaginal bacteria were tested for their ability to secrete histamine from rat peritoneal mast cells in vitro. We noticed that Mycoplasma hominis-induced histamine release was very high (up to 53.6%). The stimulation of rat mast cells with Staphylococccus cohnii, Staphylococcus coagulase(-) (two strains), Ureaplasma urealyticum, Peptostreptococcus spp., Bacteroides capillosus, Staphylococcus aureus and Streptococcus agalactiae resulted in lower but significant histamine secretion (11.2%-17.5%). Other bacteria strains (Staphylococcus epidermidids, Enterococcus faecalis, Escherichia coli, Actinomyces naeslundii (two strains) and Lactobacillus fermentum (two strains) caused very low (4.2% - 8.8%) histamine release.

  4. Participation of mast cell 5-hydroxytryptamine in the vasoconstrictor effect of neurotensin in the rat perfused hindquarter.

    PubMed

    Kérouac, R; St-Pierre, S; Rioux, F

    1984-03-01

    Neurotensin (NT) (1 X 10(-8) - 1.5 X 10(-6) g ml-1) caused a transient, dose-dependent increase in perfusion pressure in the rat perfused hindquarter. The vasoconstrictor effect of NT was associated with a short-lived, dose-dependent release of histamine and 5-hydroxytryptamine (5-HT) in the hindquarter effluent. Compound 48/80, a classical mast cell secretagogue, also elicited a vasoconstrictor effect in, and release of histamine from, the rat hindquarter. The vasoconstrictor effect and the release of histamine and 5-HT evoked by NT were much smaller in hindquarters derived from rats pretreated with compound 48/80 for 4 days to cause mast cell depletion than in hindquarters derived from control rats. The mast cell inhibitor cromoglycate (4 mg ml-1) inhibited by about 50% the histamine releasing effect and vasoconstriction produced by the lowest concentrations of NT utilized. The histamine releasing effect of compound 48/80 was more sensitive to blockade by cromoglycate than that of NT. The steroidal antiinflammatory and antiallergic drug dexamethasone did not affect the histamine and 5-HT releasing effect of NT. The vasoconstrictor effects of NT, compound 48/80 and 5-HT were markedly reduced by the 5-HT receptor antagonist methysergide (1 X 10(-7) g ml-1). Histamine (1 X 10(-6) - 10(-4) g ml-1) evoked a decrease in perfusion pressure in hindquarters pre-exposed to noradrenaline. The results suggest the participation of mast cell 5-HT in the vasoconstrictor effect of NT in the rat perfused hindquarter.

  5. Effect of methylmercury on the rat mast cell degranulation

    NASA Astrophysics Data System (ADS)

    Graevskaya, E. E.; Yasutake, A.; Aramai, R.; Rubin, A. B.

    2003-05-01

    Methylmercury is the well-known neurotoxicant as weil as a modulator of the immune system. We investigated the effects of MeHg on the rat mast cell degranulation induced by nonimmunological stimuli (the selective liberator of histamine, compound 48/80, and calcium ionophore A23187) both in vivo and in vitro. In 8, 12 and 15 days afterthe final administration of MeHg we observed the suppression of calcium ionophore A23187-and 48/80-induced histamine release, which enhanced with time. In experiments in vitro incubation of peritoneal mast cells with MeHg alone in the dose range 10^{-8} to 10^{-6} did not induce mast cell degranulation, however modified the activation of mast cells by compound 48/80, and calcium ionophore A23187. We observed activation of stimulated secretion by preliminary incubation with low dose of MeHg 10^{-8} M and inhibition by dose of MeHg 10^{-6} M. These results show that MeHg treatment can modify mast cell function in vivo and in vitro and provide insight into the understanding what role this cell has in the pathogenesis of Minamata disease-comlected disorders.

  6. Communication between mast cells and rat submucosal neurons.

    PubMed

    Bell, Anna; Althaus, Mike; Diener, Martin

    2015-08-01

    Histamine is a mast cell mediator released e.g. during food allergy. The aim of the project was to identify the effect of histamine on rat submucosal neurons and the mechanisms involved. Cultured submucosal neurons from rat colon express H1, H2 and H3 receptors as shown by immunocytochemical staining confirmed by reverse transcriptase polymerase chain reaction (RT-PCR) with messenger RNA (mRNA) isolated from submucosal homogenates as starting material. Histamine evoked a biphasic rise of the cytosolic Ca(2+) concentration in cultured submucosal neurons, consisting in a release of intracellularly stored Ca(2+) followed by an influx from the extracellular space. Although agonists of all three receptor subtypes evoked an increase in the cytosolic Ca(2+) concentration, experiments with antagonists revealed that mainly H1 (and to a lesser degree H2) receptors mediate the response to histamine. In coculture experiments with RBL-2H3 cells, a mast cell equivalent, compound 48/80, evoked an increase in the cytosolic Ca(2+) concentration of neighbouring neurons. Like the response to native histamine, the neuronal response to the mast cell degranulator was strongly inhibited by the H1 receptor antagonist pyrilamine and reduced by the H2 receptor antagonist cimetidine. In rats sensitized against ovalbumin, exposure to the antigen induced a rise in short-circuit current (I sc) across colonic mucosa-submucosa preparations without a significant increase in paracellular fluorescein fluxes. Pyrilamine strongly inhibited the increase in I sc, a weaker inhibition was observed after blockade of protease receptors or 5-lipoxygenase. Consequently, H1 receptors on submucosal neurons seem to play a pivotal role in the communication between mast cells and the enteric nervous system. PMID:25224285

  7. Quantitative changes in mast cells and microvascular pattern associated with dietary gastric ulceration in rats.

    PubMed

    Jayaraj, A P; Tovey, F I; Riley, P A; Clark, C G

    1985-01-01

    The regional distribution of mast cells and the microvascular pattern in the stomach of Wistar rats fed on an ulcerogenic diet were compared with those of control animals. Mounts of the distended stomach were made and stained for blood vessels and mast cells in the subserosal layer. Measurements made under dark ground illumination in 12 operationally defined regions of the serosa demonstrated that the stomach wall in the region around the oesophagus is more richly vascularised and possesses a greater number of mast cells (60 cells per mm2) than other regions. Changes in the mast cells and microvasculature were observed in rats fed an ulcerogenic diet, notably in the zone around the oesophagus, where more than 30% mast cells were degranulated and the mean vascular diameter increased by 26%. The severity of the vascular changes correlated with the location of the ulcers of which 50% were in the zone surrounding the oesophagus.

  8. Effects of a Moderately Lower Temperature on the Proliferation and Degranulation of Rat Mast Cells

    PubMed Central

    Wang, Ruoyu; Yin, Xiaoqin; Zhang, Hui; Wang, Jiwei; Chen, Lin; Chen, Jingwen; Han, Xiaodong; Xiang, Zou; Li, Dongmei

    2016-01-01

    Mast cells are traditionally considered as key effector cells in IgE-mediated allergic diseases. However, the roles of mast cells have also been implicated in diverse physiological and pathological processes. Mast cells are distributed in various organs and tissues of various species. Some of the organs and tissues, such as testis, skin, and the upper part of the respiratory tract, have a temperature that is lower than the body's core temperature. The purpose of the present study was to investigate the effects of a lower temperature on the proliferation and degranulation of rat mast cells. Here, we demonstrate that cell growth was retarded at 35°C compared to 37°C for both rat peritoneal mast cells (RPMC) and RBL-2H3, a rat mast cell line. Furthermore, RPMC became more susceptible to degranulation at 35°C compared to 37°C. In contrast, degranulation of RBL-2H3 was not as sensitive to temperature change as RPMC. The functionality of mast cells in unique organs with a lower temperature warrants further analysis. PMID:27195304

  9. Developmental changes of mast cell populations in the cerebral meninges of the rat.

    PubMed

    Michaloudi, Helen; Batzios, Christos; Chiotelli, Maria; Papadopoulos, Georgios C

    2007-10-01

    It is known that both the dura and the pia mater attract and support the differentiation of mast cells. The present study shows that unevenly distributed mast cells in the cerebral meninges of the rat can be found in perivascular sites and vessel ramification points, but can also be unrelated to the meningeal vasculature. It also documents changes in the number, localization and staining preferences of the mast cells in the two meninges of the developing and mature rat brain. Quantitative examination of all types of histochemically differentiated meningeal mast cells reveals no major (although some exist) differences between right and left side subpopulations, but strongly suggests a different origin and fate of the dural and the pial mast cells. The number of dural mast cells, already high from postnatal day 0, although declining from postnatal day 21 onwards, remains conspicuous up to postnatal day 180. In contrast, pial mast cells are comparatively very few in the first day of the postnatal life, and despite a transient significant increase in the following two weeks, they reach almost zero levels from postnatal day 21.

  10. The Lectin ArtinM Induces Recruitment of Rat Mast Cells from the Bone Marrow to the Peritoneal Cavity

    PubMed Central

    de Almeida Buranello, Patricia Andressa; Moulin, Maria Raquel Isnard; Souza, Devandir Antonio; Jamur, Maria Célia; Roque-Barreira, Maria Cristina; Oliver, Constance

    2010-01-01

    Background The D-mannose binding lectin ArtinM is known to recruit neutrophils, to degranulate mast cells and may have potential therapeutic applications. However, the effect of ArtinM on mast cell recruitment has not been investigated. Methodology Male Wistar rats were injected i.p. with ArtinM or ConA (control). The ability of the lectin to degranulate peritoneal and mesenteric mast cells was examined. Recruitment of mast cells to the peritoneal cavity and mesentery after ArtinM injection was examined with or without depletion of peritoneal mast cells by distilled water. Results ArtinM degranulated both peritoneal and mesentery mast cells in vitro. Three days after i.p. injection of the lectin there were reduced numbers of mast cells in the peritoneal lavage, while at 7 days post injection of ArtinM, the number of peritoneal mast cells was close to control values. Since immature mast cells are recruited from the bone marrow, the effect of the lectin on bone marrow mast cells was examined. Injection of ArtinM resulted in an increased number of mast cells in the bone marrow. To determine if degranulation of mast cells in the peritoneal cavity was required for the increase in bone marrow mast cells, the peritoneal cavity was depleted of mast cells with ultrapure water. Exposure to ArtinM increased the number of mast cells in the bone marrow of rats depleted of peritoneal mast cells. Conclusions The ArtinM induced recruitment of mast cells from the bone marrow to the peritoneal cavity may partially explain the therapeutic actions of ArtinM. PMID:20339538

  11. Mast cells respond to urticating extract from lepidoptera larva Morpheis ehrenbergii in the rat.

    PubMed

    Galicia-Curiel, María Fernanda; Quintanar, J Luis; Jiménez, Mariela; Salinas, Eva

    2014-01-01

    Mast cells and histamine participate in toxic effects of hairs from some caterpillars. This study reports that a crude extract of Morpheis ehrenbergii caterpillar hairs induces in vitro mast cells activation, triggers the release of histamine and causes a rapid urticarial reaction in the rat skin. Heating of the extract abolishes the inflammatory reaction. These results suggest that the use of antihistamines may improve the adverse skin reactions caused by the Mexican caterpillar M. ehrenbergii.

  12. [Sex differences in neuromodulation of mucosal mast cells in the rat jejunum].

    PubMed

    Gottwald, T; Becker, H D; Stead, R H

    1997-01-01

    The effect of electrical stimulation of both cervical vagal nerves on mucosal mast cells in the jejunum was investigated in an in vivo animal model with rats of both sexes. Males showed a significant increase of mast cell densities after electrical stimulation (1.0 mA, 5 Hz, 5 ms, 12 min) in the lamina propria. Simultaneously, we observed a significant increase of tissue histamine levels (ANOVA: P < 0.05), whereas serum levels remained unchanged. However, even though females had significantly higher levels throughout compared to males (ANOVA: P < 0.05), they did not show any significant reaction to electrical stimulation. These in vivo data support morphological and in vitro data from other investigators, who hypothesized a functional interaction between mucosal mast cells and nerves. However, degranulation seems to be a poor in situ indicator for mast-cell stimulation, as mast-cell densities increased in males, while the percentage of degranulated cells remained the same in all groups (about 40%). Instead, electrical stimulation of the vagal nerve seems to trigger histamine synthesis, or simply stabilization of mast cells. Interestingly, this phenomenon seems to be sex-dependent, suggesting a regulatory role for sex hormones in this scenario.

  13. Effects of long-term administration of cancer-promoting substances on oral subepithelial mast cells in the rat.

    PubMed

    Sand, L; Hilliges, M; Larsson, P A; Wallstrom, M; Hirsch, J M

    2002-01-01

    The role of oral subepithelial mast cells in the defence against tumours is a matter of controversy. The effect of established and suggested carcinogens, such as the carcinogen 4-nitroquinoline-N-oxide (4-NQO) and Herpes simplex virus type 1 (HSV-1), in combination with oral snuff on lower lip subepithelial mast cells (MC) was studied in rats. The rats were exposed to prolonged use of oral snuff. The test substances were administered in a surgically created canal in the lower lip of the rats. There were 15 rats in each test group and 10 rats in the control group. The amount of countable subepithelial mast cells decreased significantly when the rat oral mucosa was exposed to the oral carcinogen 4-NQO but the effect of oral snuff and HSV-1 infection was weak. Our findings suggest that mast cells play a role in immunological cell defence against chemical carcinogens. Further studies are needed to clarify the mechanisms. PMID:12529973

  14. Intestinal mucosal mast cells in normal and nematode-infected rat intestines are in intimate contact with peptidergic nerves.

    PubMed Central

    Stead, R H; Tomioka, M; Quinonez, G; Simon, G T; Felten, S Y; Bienenstock, J

    1987-01-01

    Inflammatory or allergic conditions, as well as situations where healing and repair processes occur, are characterized by the presence of increased numbers of mast cells. Previous work on the effect of neuropeptides on mast cell mediator release showed that only substance P caused such release from intestinal mucosal mast cells [Shanahan, F., Denburg, J. A., Fox, J., Bienenstock, J. & Befus, A. D. (1985) J. Immunol. 135, 1331-1337]. Accordingly, we investigated the microanatomical relationship between mast cells and enteric nerves in normal rat intestine and parasite-infected rat intestine, in which mucosal mast cell hyperplasia occurs. Combined immunohistochemistry for neuron-specific enolase and staining with alcian blue at pH 0.5 was employed on paraffin-embedded sections of normal and Nippostrongylus brasiliensis-infected rat jejunum. Sixty-seven percent of intestinal mucosal mast cells were touching subepithelial nerves, and an additional 20% were within 2 micron of nerves. Assessment of the proportion of the lamina propria occupied by mast cells (12.5%), the average mast cell area (121 +/- 28 microns 2), and the density of enteric nerves (one per 788 +/- 151 microns 2) suggested that the association was 5 times greater than would be expected by chance alone (P less than 0.0001). In consecutive sections, the nerves in contact with mast cells were also shown to contain substance P and/or calcitonin-gene-related peptide. Electron microscopy confirmed this association: 8% of the mast cells in infected rats exhibited membrane-membrane contact with unmyelinated axons containing 70- to 170-nm dense-core vesicles, and an additional 31% were situated less than 250 nm from nerves. Other mast cells appeared to embrace nerve bundles through the projection of lamellopodia. These data provide systematic quantitative evidence that a structural foundation for communication between the immune and nervous systems exists in the rat gastrointestinal tract. Images PMID:2437589

  15. Agarwood Inhibits Histamine Release from Rat Mast Cells and Reduces Scratching Behavior in Mice

    PubMed Central

    Inoue, Eiji; Shimizu, Yasuharu; Masui, Ryo; Tsubonoya, Tomoe; Hayakawa, Tomomi; Sudoh, Keiichi

    2016-01-01

    Objectives: This study was conducted to clarify the effects of agarwood on histamine release from mast cells in rats and on the scratching behaviors in mice. Methods: Histamine release from rat mast cells induced by compound 48/80 or concanavalin A (Con A) and compound 48/80-induced scratching behavior in mice were examined to investigate the effects of agarwood. The hyaluronidase activity and the 3’,5’-cyclic adenosine monophosphate (cAMP) levels in mast cells were examined to investigate the mechanisms for the inhibition of histamine release. The correlation between the inhibitory effects of agarwood on histamine release and the content of its typical ingredients, a 2-(2-phenylethyl)chromone derivatives, was analyzed using thin-layer chromatography. Results: Agarwood showed an inhibitory effect on mast-cell histamine release induced by compound 48/80 or Con A without any effect on hyaluronidase activity; this effect involves an increase in the cAMP levels in mast cells. Oral administration of agarwood showed an inhibitory effect on compound 48/80-induced scratching behavior in mice. The inhibitory effects of agarwood on histamine release were quite different, depending on the area where the agarwood was produced, its quality, and its market price. No correlation was found between the inhibitory effects of agarwood on histamine release and the typical ingredients of agarwood, which are 2-(2-phenylethyl)chromone derivatives. Conclusion: These results show that agarwood inhibits histamine release from mast cells partially through an increase in the cAMP levels in cells. We suggest that some active ingredients of agarwood must be effective on oral intake and that agarwood can be used to treat patients with a number of conditions, including urticaria, atopic dermatitis, and bronchial asthma, in which an increase in histamine release occurs. Differences in the pharmacological effects of this crude drug among markets may provide important information for the quality

  16. Agarwood Inhibits Histamine Release from Rat Mast Cells and Reduces Scratching Behavior in Mice

    PubMed Central

    Inoue, Eiji; Shimizu, Yasuharu; Masui, Ryo; Tsubonoya, Tomoe; Hayakawa, Tomomi; Sudoh, Keiichi

    2016-01-01

    Objectives: This study was conducted to clarify the effects of agarwood on histamine release from mast cells in rats and on the scratching behaviors in mice. Methods: Histamine release from rat mast cells induced by compound 48/80 or concanavalin A (Con A) and compound 48/80-induced scratching behavior in mice were examined to investigate the effects of agarwood. The hyaluronidase activity and the 3’,5’-cyclic adenosine monophosphate (cAMP) levels in mast cells were examined to investigate the mechanisms for the inhibition of histamine release. The correlation between the inhibitory effects of agarwood on histamine release and the content of its typical ingredients, a 2-(2-phenylethyl)chromone derivatives, was analyzed using thin-layer chromatography. Results: Agarwood showed an inhibitory effect on mast-cell histamine release induced by compound 48/80 or Con A without any effect on hyaluronidase activity; this effect involves an increase in the cAMP levels in mast cells. Oral administration of agarwood showed an inhibitory effect on compound 48/80-induced scratching behavior in mice. The inhibitory effects of agarwood on histamine release were quite different, depending on the area where the agarwood was produced, its quality, and its market price. No correlation was found between the inhibitory effects of agarwood on histamine release and the typical ingredients of agarwood, which are 2-(2-phenylethyl)chromone derivatives. Conclusion: These results show that agarwood inhibits histamine release from mast cells partially through an increase in the cAMP levels in cells. We suggest that some active ingredients of agarwood must be effective on oral intake and that agarwood can be used to treat patients with a number of conditions, including urticaria, atopic dermatitis, and bronchial asthma, in which an increase in histamine release occurs. Differences in the pharmacological effects of this crude drug among markets may provide important information for the quality

  17. Induction of mast cell proliferation, maturation, and heparin synthesis by the rat c-kit ligand, stem cell factor

    SciTech Connect

    Tsai, M.; Takeishi, Takashi; Geissler, E.N. ); Thompson, H.; Metcalfe, D.D. ); Langley, K.E.; Zsebo, K.M.; Galli, S.J. )

    1991-07-15

    The authors investigated the effects of a newly recognized multifunctional growth factor, the c-kit ligand stem cell factor (SCF), on mouse mast cell proliferation and phenotype. Recombinant rat SCF{sup 164} (rrSCF{sup 164}) induced the development of large numbers of dermal mast cells in normal mice in vivo. Many of these mast cells had features of connective tissue-type mast cells (CTMC), in that they were reactive both with the heparin-binding fluorescent dye berberine sulfate and with safranin. In vitro, rrSCF{sup 164} induced the proliferation of cloned interleukin 3 (IL-3)-dependent mouse mast cells and primary populations of IL-3-dependent, bone marrow-derived cultured mast cells (BMCMC), which represent immature mast cells, and purified peritoneal mast cells, which represent a type of mature CTMC> BMCMC maintained in rrSCF{sup 164} not only proliferated but also matured. These findings identify SCF as a single cytokine that can induce immature, IL-3-dependent mast cells to mature and to acquire multiple characteristics of CTMC. These findings also directly demonstrate that SCF can regulate the development of a cellular lineage expressing c-kit through effects on both proliferation and maturation.

  18. Effects of long-acting beta 2-adrenoceptor agonists on mast cells of rat, guinea pig, and human.

    PubMed

    Lau, H Y; Wong, P L; Lai, C K; Ho, J K

    1994-10-01

    The effects of two recently developed long-acting beta 2-adrenoceptor agonists, formoterol and salmeterol, on mast cells from different sources were compared with those of the prototype short-acting analogue, salbutamol. With the exception of high concentrations of salmeterol (> 10(-5) M), none of the tested beta 2-adrenoceptor agonists inhibited the anti-IgE-induced histamine release from rat peritoneal mast cells. In contrast, all three compounds dose dependently inhibited the immunologically induced histamine release from isolated lung mast cells of guinea pig and human at concentrations < or = 10(-5) M.

  19. Contribution of mast cells and snake venom metalloproteinases to the hyperalgesia induced by Bothrops jararaca venom in rats.

    PubMed

    Bonavita, André Gustavo C; da Costa, Aline S; Pires, Ana Lucia A; Neves-Ferreira, Ana G C; Perales, Jonas; Cordeiro, Renato S B; Martins, Marco A; e Silva, Patrícia M R

    2006-06-15

    Bothrops jararaca venom (Bjv) is known to induce local inflammation and severe pain. Since, mast cells are able to secrete mediators involved in algesic processes, in this study we examined the putative role of these cells in the hyperalgesia triggered by Bjv in the rat paw. We noted that treatment with mast cell stabilizer sodium cromoglicate as well as with histamine and 5-hydroxytriptamine receptor antagonists meclizine and methysergide, respectively, inhibited the Bjv-induced hyperalgesia. In addition, we showed that stimulation of isolated rat peritoneal mast cells with Bjv in vitro resulted in the release of stored and neo-generated inflammatory mediators such as histamine and leukotriene C(4), respectively. Bjv-induced histamine secretion was clearly sensitive to treatment with sodium cromoglicate and sodium nedocromil. We further observed that metalloproteinase inhibitors 1,10-phenantroline and DM43 inhibited mast cell degranulation in vitro, under conditions where inhibitors of phospholipase A(2) as well as of serine- and cysteine-proteinases were inactive. Altogether, our findings indicate that mast cells seem to contribute to the hyperalgesia caused by Bjv in the rat paw, and also provide evidence that this response might be dependent on the ability of the Bjv to activate directly mast cells. PMID:16730041

  20. Na+ -K+ pump activity in rat peritoneal mast cells: inhibition by extracellular calcium.

    PubMed Central

    Knudsen, T.; Johansen, T.

    1989-01-01

    1. Pure populations of rat peritoneal mast cells were used to study cellular potassium uptake. The radioactive potassium analogue, 86rubidium, was used as a tracer for potassium for measurements of the activity of the cellular potassium uptake process. 2. The ouabain-sensitive and the ouabain-resistant potassium (86rubidium) uptake of mast cells incubated in the presence of calcium, 1 mmol l-1, were very low, 52 and 147 pmol per 10(6) cells min-1. 3. Calcium-deprivation of the cells uncovered a large capacity ouabain-sensitive potassium (86rubidium) uptake mechanism. The activity of the uptake mechanism was decreased by reintroduction of calcium into the cell suspension, and it was dependent on cellular energy metabolism, temperature and pH. 4. The potassium (86rubidium) uptake of mast cells incubated in a calcium-free medium occurs through an active and ouabain-sensitive mechanism that has the nature of an enzyme, and it is mediated by the Na+ -K+ pump located in the plasma membrane. It is demonstrated that the activity of the Na+ -K+ pump mechanism is inhibited by low concentrations of extracellular calcium (0.1-1.2 mmol l-1). The possibility is discussed that calcium-deprivation may increase the pump activity by increasing the permeability of the plasma membrane for Na+. PMID:2743077

  1. Elemental levels in mast cell granules differ in sections from normal and diabetic rats: an X-ray microanalysis study

    SciTech Connect

    Kendall, M.D.

    1988-03-01

    Mast cells around the thymus of rats stain red with alcian blue and safranin indicating that the mast cells are probably of the peritoneal (connective tissue) type. After the onset of streptozotocin induced diabetes some cells contain both red and blue granules and blue staining cells may appear. X-ray microanalysis of frozen freeze-dried sections from diabetic male CSE Wistar rats showed electron dense granules to have similar amounts of S to normal rat mast cell granules but reduced levels of Na, Mg, P, Cl and K. Two cells also had electron lucent granules with very high levels of Na, Cl, K and Ca and reduced concentrations of S. The differences in elemental composition suggest that the mast cells from diabetic rats are not immature, but are related to the condition of induced diabetes, and that granules of very different composition can occur within a single cell. X-ray microanalysis has given an insight into mast cell granule elemental content which was not possible by conventional biochemical methods.

  2. Effect of picumast on histamine release from rat cardiac and peritoneal mast cells.

    PubMed

    Wan, B Y; Peh, K H; Assem, E S

    1991-05-01

    Compound 48/80-induced histamine release (HR) from the isolated perfused rat heart was markedly and significantly inhibited by picumast (PIC), possibly by acting as a calmodulin antagonist (CMA) or membrane stabilizer. Trifluoperazine (TFP, another CMA in clinical use) had a similar effect. However, an action as CMA being the basis of inhibition of HR could not be confirmed in another 'allergy' model, namely HR from rat peritoneal mast cells (RPMC). PIC, TFP and two other CMA, W7 and N-(4-aminobutyl)-5-chloro-1-naphthalenesulfonamide) failed consistently to inhibit 48/80-induced HR from RPMC, and when used on their own at high concentration these compounds caused HR. PIC and TFP also potentiated the heat-induced haemolysis of rat erythrocytes, i.e. lacked membrane stabilizing effect in this model.

  3. Influence of laser and LED irradiation on mast cells of cutaneous wounds of rats with iron deficiency anemia

    NASA Astrophysics Data System (ADS)

    Becher Rosa, Cristiane; Oliveira Sampaio, Susana C. P.; Monteiro, Juliana S. C.; Ferreira, Maria F. L.; Zanini, Fátima A. A.; Santos, Jean N.; Cangussú, Maria Cristina T.; Pinheiro, Antonio L. B.

    2011-03-01

    This work aimed to study histologically the effect of Laser or LED phototherapy on mast cells on cutaneous wounds of rats with iron deficiency. 18 rats were used and fed with special peleted iron-free diet. An excisional wound was created on the dorsum of each animal which were divided into: Group I - Control with anemia + no treatment; Group II - Anemia + Laser; Group III - Anemia + LED; Group IV - Healthy + no treatment; Group V - Healthy + Laser; Group VI - Healthy + LED. Irradiation was performed using a diode Laser (λ660nm, 40mW, CW, total dose of 10J/cm2, 4X2.5J/cm2) or a RED-LED ( λ700nm, 15mW, CW, total dose of 10J/cm2). Histological specimens were routinely processed, cut and stained with toluidine blue and mast cell counts performed. No significant statistic difference was found between groups as to the number of degranulated, non-degradulated or total mast cells. Greater mean values were found for degranulated mast cells in the Anemia + LED. LED irradiation on healthy specimens resulted in a smaller number of degranulated mast cells. Our results leads to conclude that there are no significant differences in the number of mast cells seven days after irradiation following Laser or LED phototherapy.

  4. Alpha-lipoic acid and N-acetylcysteine protects intensive swimming exercise-mediated germ-cell depletion, pro-oxidant generation, and alteration of steroidogenesis in rat testis.

    PubMed

    Jana, Kuladip; Dutta, Ananya; Chakraborty, Pratip; Manna, Indranil; Firdaus, Syed Benazir; Bandyopadhyay, Debasish; Chattopadhyay, Ratna; Chakravarty, Baidyanath

    2014-09-01

    Prolonged and strenuous exercise has been proposed as a possible source of male-factor infertility. Forced intensive swimming has also been identified as one source of a dysfunctional male reproduction system. The present study evaluated the possible protective role of α-lipoic acid and N-acetylcysteine (NAC) on intensive swimming-induced germ-cell depletion in adult male rats. Forced exhaustive swimming of 1 hr/day, 6 days/week for 8 consecutive weeks resulted in a significant (P < 0.05) reduction in epididymal sperm; testicular androgenic enzyme activities; and plasma and intra-testicular testosterone; and produced different types of germ cells in the seminiferous epithelium cycle. Conversely, plasma corticosterone levels and sperm-head abnormalities increased. Western-blot analysis showed a considerable decrease in testicular StAR protein expression whereas reverse-transcriptase PCR analysis showed no significant change in cytochrome P450scc (Cyp11a1) gene expression. Significant (P < 0.05) elevation in testicular reactive oxygen species (ROS), lipid peroxidation, protein carbonyl content versus reduction in glucose-6-phosphate dehydrogenase, glutathione peroxidase, glutathione S-transferase, and caspase-3 activities along with a depletion in the glutathione pool, mitochondrial membrane potential (▵ψm ), and intracellular ATP generation. A considerable level of DNA damage in testicular spermatogenic cells were also noted following forced extensive swimming. Alpha-lipoic acid and NAC supplementation prevented the swimming-induced testicular spermatogenic and steroidogenic disorders by lowering ROS generation. We therefore conclude that intensive forced swimming causes germ-cell depletion through the generation of ROS and depletion of steroidogenesis in the testis, which can be protected by the co-administration of α-lipoic acid and NAC. PMID:25104294

  5. Suppressed histamine release from rat peritoneal mast cells by ultraviolet B irradiation: decreased diacylglycerol formation as a possible mechanism

    SciTech Connect

    Danno, K.; Fujii, K.; Tachibana, T.; Toda, K.; Horio, T.

    1988-06-01

    This study was designed to investigate the effect of ultraviolet B (UVB) irradiation on mast cell functions. Purified mast cells obtained from rat peritoneal cavity were irradiated with UVB and subsequently exposed to a degranulator, compound 48/80, or the calcium ionophore A-23187. The amount of histamine released from mast cells measured by the enzyme isotopic assay was significantly decreased by UVB irradiation (100-400 mJ/cm2). Within this dose range, UVB alone was not cytotoxic to the cells because it did not induce histamine release. The suppression was observed when mast cells were subjected to degranulation without intervals after UVB irradiation, and even after 5 h postirradiation. The wavelength of 300 nm from a monochromatic light source showed the maximum effect. When mast cells prelabeled with (/sup 3/H)arachidonate were irradiated and challenged by compound 48/80, label accumulation in diacylglycerol produced by the phosphatidylinositol cycle was considerably decreased by UVB irradiation. From these results, we hypothesize that, within an adequate irradiation dose, UVB irradiation suppresses histamine release from mast cells, probably by causing noncytotoxic damage to the membrane phospholipid metabolism, which is tied to the degranulation mechanisms.

  6. Increased numbers of mast cells in the hyperplastic buccal mucosa of the zinc-deficient rat.

    PubMed

    Kreavich, M E; Meyer, J; Waterhouse, J P

    1981-02-01

    Six weanling male Sprague Dawley rats were fed a diet containing 0.4 ppm Zn and seven were fed an identical diet except for 40 ppm Zn. After 4 weeks, specimens of buccal mucosa in the region facing the molar teeth were removed. Paraffin sections, cut at 6 micron, were stained with toluidine blue, and tracings made of five sections per animal, spaced no less than 60 micron apart. Counts of mast cells of five sections length of section were made in a superficial zone of the lamina propria of 50 micron width and a deeper zone of 250 micron width. The average number of mast cells, per mm in the subepithelial zone of the experimental animals was 15.4, the range 9.2-33.1. The control average was 4.0; the range was 2.9-5.3. No increase was found in the deeper zone. The epithelium was parakeratotic and its thickness was increased two-fold. In the peripheral portion of the section, cellular and keratin layers were evenly increased in thickness, but in the central portion a disproportionate, nearly four-fold increase occurred in the keratin layer and a lesser increase in the cellular layer.

  7. Kupffer cell depletion protects against the steatosis, but not the liver damage, induced by marginal-copper, high-fructose diet in male rats.

    PubMed

    Song, Ming; Schuschke, Dale A; Zhou, Zhanxiang; Zhong, Wei; Zhang, Jiayuan; Zhang, Xiang; Wang, Yuhua; McClain, Craig J

    2015-06-01

    High-fructose feeding impairs copper status and leads to low copper availability, which is a novel mechanism in obesity-related fatty liver. Copper deficiency-associated hepatic iron overload likely plays an important role in fructose-induced liver injury. Excess iron in the liver is distributed throughout hepatocytes and Kupffer cells (KCs). The aim of this study was to examine the role of KCs in the pathogenesis of nonalcoholic fatty liver disease induced by a marginal-copper high-fructose diet (CuMF). Male weanling Sprague-Dawley rats were fed either a copper-adequate or a marginally copper-deficient diet for 4 wk. Deionized water or deionized water containing 30% fructose (wt/vol) was also given ad libitum. KCs were depleted by intravenous administration of gadolinium chloride (GdCl3) before and/or in the middle of the experimental period. Hepatic triglyceride accumulation was completely eliminated with KC depletion in CuMF consumption rats, which was associated with the normalization of elevated plasma monocyte chemoattractant protein-1 (MCP-1) and increased hepatic sterol regulatory element binding protein-1 expression. However, hepatic copper and iron content were not significantly affected by KC depletion. In addition, KC depletion reduced body weight and epididymal fat weight as well as adipocyte size. Plasma endotoxin and gut permeability were markedly increased in CuMF rats. Moreover, MCP-1 was robustly increased in the culture medium when isolated KCs from CuMF rats were treated with LPS. Our data suggest that KCs play a critical role in the development of hepatic steatosis induced by marginal-copper high-fructose diet.

  8. Kupffer cell depletion protects against the steatosis, but not the liver damage, induced by marginal-copper, high-fructose diet in male rats.

    PubMed

    Song, Ming; Schuschke, Dale A; Zhou, Zhanxiang; Zhong, Wei; Zhang, Jiayuan; Zhang, Xiang; Wang, Yuhua; McClain, Craig J

    2015-06-01

    High-fructose feeding impairs copper status and leads to low copper availability, which is a novel mechanism in obesity-related fatty liver. Copper deficiency-associated hepatic iron overload likely plays an important role in fructose-induced liver injury. Excess iron in the liver is distributed throughout hepatocytes and Kupffer cells (KCs). The aim of this study was to examine the role of KCs in the pathogenesis of nonalcoholic fatty liver disease induced by a marginal-copper high-fructose diet (CuMF). Male weanling Sprague-Dawley rats were fed either a copper-adequate or a marginally copper-deficient diet for 4 wk. Deionized water or deionized water containing 30% fructose (wt/vol) was also given ad libitum. KCs were depleted by intravenous administration of gadolinium chloride (GdCl3) before and/or in the middle of the experimental period. Hepatic triglyceride accumulation was completely eliminated with KC depletion in CuMF consumption rats, which was associated with the normalization of elevated plasma monocyte chemoattractant protein-1 (MCP-1) and increased hepatic sterol regulatory element binding protein-1 expression. However, hepatic copper and iron content were not significantly affected by KC depletion. In addition, KC depletion reduced body weight and epididymal fat weight as well as adipocyte size. Plasma endotoxin and gut permeability were markedly increased in CuMF rats. Moreover, MCP-1 was robustly increased in the culture medium when isolated KCs from CuMF rats were treated with LPS. Our data suggest that KCs play a critical role in the development of hepatic steatosis induced by marginal-copper high-fructose diet. PMID:25813056

  9. The mast cell stabilizer sodium cromoglycate reduces histamine release and status epilepticus-induced neuronal damage in the rat hippocampus.

    PubMed

    Valle-Dorado, María Guadalupe; Santana-Gómez, César Emmanuel; Orozco-Suárez, Sandra Adela; Rocha, Luisa

    2015-05-01

    Experiments were designed to evaluate changes in the histamine release, mast cell number and neuronal damage in hippocampus induced by status epilepticus. We also evaluated if sodium cromoglycate, a stabilizer of mast cells with a possible stabilizing effect on the membrane of neurons, was able to prevent the release of histamine, γ-aminobutyric acid (GABA) and glutamate during the status epilepticus. During microdialysis experiments, rats were treated with saline (SS-SE) or sodium cromoglycate (CG-SE) and 30 min later received the administration of pilocarpine to induce status epilepticus. Twenty-four hours after the status epilepticus, the brains were used to determine the neuronal damage and the number of mast cells in hippocampus. During the status epilepticus, SS-SE group showed an enhanced release of histamine (138.5%, p = 0.005), GABA (331 ± 91%, p ≤ 0.001) and glutamate (467%, p ≤ 0.001), even after diazepam administration. One day after the status epilepticus, SS-SE group demonstrated increased number of mast cells in Stratum pyramidale of CA1 (88%, p < 0.001) and neuronal damage in dentate gyrus, CA1 and CA3. In contrast to SS-SE group, rats from the CG-SE group showed increased latency to the establishment of the status epilepticus (p = 0.048), absence of wet-dog shakes, reduced histamine (but not GABA and glutamate) release, lower number of mast cells (p = 0.008) and reduced neuronal damage in hippocampus. Our data revealed that histamine, possibly from mast cells, is released in hippocampus during the status epilepticus. This effect may be involved in the subsequent neuronal damage and is diminished with sodium cromoglycate pretreatment.

  10. The antinociception of oxytocin on colonic hypersensitivity in rats was mediated by inhibition of mast cell degranulation via Ca(2+)-NOS pathway.

    PubMed

    Gong, Liping; Li, Jing; Tang, Yan; Han, Ting; Wei, Chuanfei; Yu, Xiao; Li, Jingxin; Wang, Rong; Ma, Xuelian; Liu, Kejing; Geng, Lingyun; Liu, Shaozhuang; Yan, Bing; Liu, Chuanyong

    2016-01-01

    This study was conducted to investigate the effects of oxytocin (OT) on visceral hypersensitivity/pain and mast cell degranulation and the underlying mechanisms. We found that oxytocin receptor (OTR) was expressed in colonic mast cells in humans and rats, as well as in human mast cell line-1 (HMC-1), rat basophilic leukemia cell line (RBL-2H3) and mouse mastocytoma cell line (P815). OT decreased 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced visceral hypersensitivity, colonic mast cell degranulation and histamine release after mast cell degranulation in rats. Also, OT attenuated the compound 48/80 (C48/80)-evoked histamine release in P815 cells and inward currents, responsible for the mast cell degranulation, in HMC-1, RBL-2H3 and P815 cells. Moreover, these protective effects of OT against visceral hypersensitivity and mast cell degranulation were eliminated by coadministration of OTR antagonist atosiban or a nonselective inhibitor of nitric oxide synthase (NOS), NG-Methyl-L-arginine acetate salt (L-NMMA). Notably, OT evoked a concentration-dependent increase of intracellular Ca(2+) in HMC-1, RBL-2H3 and P815 cells, which was responsible for the activation of neuronal NOS (NOS1) and endothelial NOS (NOS3). Our findings strongly suggest that OT might exert the antinociception on colonic hypersensitivity through inhibition of mast cell degranulation via Ca(2+)-NOS pathway. PMID:27538454

  11. The antinociception of oxytocin on colonic hypersensitivity in rats was mediated by inhibition of mast cell degranulation via Ca2+-NOS pathway

    PubMed Central

    Gong, Liping; Li, Jing; Tang, Yan; Han, Ting; Wei, Chuanfei; Yu, Xiao; Li, Jingxin; Wang, Rong; Ma, Xuelian; Liu, Kejing; Geng, Lingyun; Liu, Shaozhuang; Yan, Bing; Liu, Chuanyong

    2016-01-01

    This study was conducted to investigate the effects of oxytocin (OT) on visceral hypersensitivity/pain and mast cell degranulation and the underlying mechanisms. We found that oxytocin receptor (OTR) was expressed in colonic mast cells in humans and rats, as well as in human mast cell line-1 (HMC-1), rat basophilic leukemia cell line (RBL-2H3) and mouse mastocytoma cell line (P815). OT decreased 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced visceral hypersensitivity, colonic mast cell degranulation and histamine release after mast cell degranulation in rats. Also, OT attenuated the compound 48/80 (C48/80)-evoked histamine release in P815 cells and inward currents, responsible for the mast cell degranulation, in HMC-1, RBL-2H3 and P815 cells. Moreover, these protective effects of OT against visceral hypersensitivity and mast cell degranulation were eliminated by coadministration of OTR antagonist atosiban or a nonselective inhibitor of nitric oxide synthase (NOS), NG-Methyl-L-arginine acetate salt (L-NMMA). Notably, OT evoked a concentration-dependent increase of intracellular Ca2+ in HMC-1, RBL-2H3 and P815 cells, which was responsible for the activation of neuronal NOS (NOS1) and endothelial NOS (NOS3). Our findings strongly suggest that OT might exert the antinociception on colonic hypersensitivity through inhibition of mast cell degranulation via Ca2+-NOS pathway. PMID:27538454

  12. Rat intestinal mast cell amines are released during nitric oxide synthase inhibition in vitro

    PubMed Central

    Northover, B. J.

    1996-01-01

    Inhibition of nitric oxide synthase increases microvascular permeability in rat small intestinal villi. To determine the mechanism(s) whereby this occurs we have perfused the vasculature of rat isolated small intestines with a gelatin-containing physiological salt solution. Inclusion of N-nitro-L-argintne methyl ester (L-NAME, 100 μM) or indomethacin (1 μM) in the perfusate increased leakage of injected colloidal carbon into microvessel walls. Pre-treatment with sodium nitroprusside (10 μM) significantly reduced the effects of both L-NAME and indomethacin, whereas carbacyclin (1 μM) only reduced the effects of indomethacin. PD151242 (1 μM) showed some antagonism towards the effects of L-NAME, but nordihydroguaiaretic acid (3 μM) was inactive. Pre-tment with cyproheptadine (10 μM) reduced the effects of both L-NAME and indomethacin, and also significantly reduced background (control) colloidal carbon leakage. Small intestines from polymixin B-treated rats showed significantly reduced colloidal carbon leakage in response to L-NAME. This suggests that the leakage-enhancing effects of both L-NAME and indomethacin in this preparation may be mediated by mast cell-derived amines. PMID:18475694

  13. Cloning of cDNAs that encode human mast cell carboxypeptidase A, and comparison of the protein with mouse mast cell carboxypeptidase A and rat pancreatic carboxypeptidases

    SciTech Connect

    Reynolds, D.S.; Gurley, D.S.; Stevens, R.L.; Austen, K.F.; Serafin, W.E. Brigham and Women's Hospital, Boston, MA ); Sugarbaker, D.J. )

    1989-12-01

    Human skin and lung mast cells and rodent peritoneal cells contain a carboxypeptidase in their secretory granules. The authors have screened human lung cDNA libraries with a mouse mast cell carboxypeptidase A (MC-CPA) cDNA probe to isolate a near-full-length cDNA that encodes human MC-CPA. The 5{prime} end of the human MC-CPA transcript was defined by direct mRNA sequencing and by isolation and partial sequencing of the human MC-CPA gene. Human MC-CPA is predicted to be translated as a 417 amino acid preproenzyme which includes a 15 amino acid signal peptide and a 94-amino acid activation peptide. The mature human MC-CPA enzyme has a predicted size of 36.1 kDa, a net positive charge of 16 at neutral pH, and 86% amino acid sequence identity with mouse MC-CPA. DNA blot analyses showed that human MC-CPA mRNA is transcribed from a single locus in the human genome. Comparison of the human MC-CPA with mouse MC-CPA and with three rat pancreatic carboxypeptidases shows that these enzymes are encoded by distinct but homologous genes.

  14. Induction of humoral immunity and pulmonary mast cells in mice and rats after immunization with aerosolized antigen.

    PubMed Central

    Ahlstedt, S; Björkstén, B; Nygren, H; Smedegård, G

    1983-01-01

    Rats (BN X Wistar) and mice (CBA/Ca) were immunized by exposure in 10-day periods to an aerosol of ovalbumin (OA). In rats this immunization resulted in IgE antibodies detectable at very low levels in bronchial washings, whereas IgG, IgA and IgM antibodies were recorded both in serum and in bronchial washings. In mice, exposure to aerosolized antigen resulted in specific IgE and IgG antibodies in serum. The levels of IgM antibodies were low and no IgA antibodies could be recorded with the enzyme-linked immunosorbent assay (ELISA). Histological examination of lung tissue from immunized rats and mice revealed increased numbers of cells with characteristics of both immature and mature mast cells. In addition, in the rats these cells were more closely located to the bronchi in immunized than in control animals. In the latter animals the mast cells were located around the blood vessels. Immature mast cells were located in the bronchiole-associated lymphatic tissue (BALT) which showed a marked proliferation in immunized animals. The findings indicate that sensitization via the airways provides possibilities to develop a model in rodents for studies of IgE-mediated allergy in the lung. Images Figure 2 Figure 3 Figure 4 Figure 5 PMID:6822403

  15. The Na+/K(+)-pump in rat peritoneal mast cells: some aspects of regulation of activity and cellular function.

    PubMed

    Knudsen, T

    1995-11-01

    The mast cell contains potent mediators of inflammation which are released after IgE-directed and non-IgE-directed stimulation of the cell. This highly specialized cell is therefore ascribed a role in the pathogenesis of disease states in which the inflammatory response plays a role for the development of the clinical symptoms. Thus, besides being of interest in basic research, studies of the cellular processes leading to release of inflammatory mediators from the mast cell also have important clinical implications. The aim of the present work has been to document the existence of the Na+/K(+)-pump in rat peritoneal mast cells, to investigate the regulation of the pump activity and to explore whether modulation of the pump activity interferes with the cellular stimulus/secretion coupling mechanism. The Na+/K(+)-pump activity following stimulation of the mast cell was also investigated. The pump activity was assessed as the ouabain-sensitive cellular potassium uptake with 86Rb+ as a tracer for potassium. The histamine release from the mast cell following IgE-directed and non-IgE directed stimulation of the cell was used as a parameter for cellular degranulation. Histamine was measured by spectrofluorometry. The finding of an ouabain-sensitive uptake mechanism in the mast cell documents the presence of a functional Na+/K(+)-pump in this cell. The pump activity is inhibited by lanthanides and by the divalent cations calcium, magnesium, barium and strontium. The pump has a large reserve capacity which probably is caused by a low intracellular concentration of sodium. This enables the pump to respond to changes in the intracellular sodium concentration. The inhibitory effect of di- and trivalent ions on the pump activity is probably a result of the inhibitory effect of these ions on the cellular sodium uptake. The digitalis glycosides, ouabain and digoxin, but not the more lipophilic drug digitoxigenin, increase both IgE-directed and non-IgE-directed histamine release

  16. Intestinal mucosal mast cells from rats infected with Nippostrongylus brasiliensis contain protease-resistant chondroitin sulfate di-B proteoglycans

    SciTech Connect

    Stevens, R.L.; Lee, T.D.G.; Seldin, D.C.; Austen, K.F.; Befus, A.D.; Bienenstock, J.

    1986-07-01

    Rats infected with the helminth Nippostrongylus brasiliensis were injected i.p. with 2 mCi of (/sup 35/S) sulfate on days 13, 15, 17, and 19 after infection. The intestines were removed from animals on day 20 or 21 after infection, the intestinal cells were obtained by collagenase treatment and mechanical dispersion of the tissue, and the /sup 35/S-labeled mucosal mast cells (MMC) were enriched to 60 to 65% purity by Percoll centrifugation. The isolated proteoglycans were of approx. 150,000 m.w., were resistant to pronase degradation, and contained highly sulfated chondroitin sulfate side chains. The presence in normal mammalian cells of chondroitin sulfate proteoglycans that contain a high percentage of the unusual disulfated di-B disaccharide has not been previously reported. The rat intestinal MMC proteoglycans are the first chondroitin sulfate proteoglycans that have been isolated from an enriched populations of normal mast cells. They are homologous to the chondroitin sulfate-rich proteoglycans of the transformed rat basophilic leumekia-1 cell and the cultured interleukin 3-dependent mouse bone marrow-derived mast cell, in that these chondroitin sulfate proteoglycans are all highly sulfated, protease-resistant proteoglycans.

  17. Study on the Dynamic Compound Structure Composed of Mast Cells, Blood Vessels, and Nerves in Rat Acupoint

    PubMed Central

    Mingfu, Luo; Xiaotong, Dong; Xiaojing, Song; Jin, Jiang; Jinling, Zhann; Ying, Han

    2013-01-01

    Background. Circulation system, immunity system, and nervous system have a close relationship with meridian phenomen. However, there is still lack of the results of dynamic changes of these structures in acupoint. The aim of this study is to explore the interrelationship by composite staining techniques. Methodology/Principal Findings. Twenty rats were separated into electroacupuncture group (EA) and control group (Con) randomly. In EA group, the Zusanli and Weishu were stimulated with the 0.1 mA for 25 min. The tissue of these acupoints was double-stained with acetylcholinesterase and Toluidine blue. The compound structure of mast cells, nervous fibers, and mast cells in the acupoint was observed. Conclusions/Significance. The blood vessels, mast cells and acetylcholinesterase responded nerves were clearly observed in acupoint tissues. EA can result in the mast cell recruitment and migration along the blood vessels and nervous bundle, which conformed the dynamic compound structure and played important roles in acupuncture. PMID:23878591

  18. Molecular species analysis of phosphatidylinositol (PI), phosphatidic acid (PA) and diacylglycerol (DG) in rat mast cells

    SciTech Connect

    Kennerly, D.A.

    1987-05-01

    The metabolism of DG, PA and PI were studied in purified rat mast cells to determine whether generally accepted pathways of PI metabolism could explain the pattern of fatty acids seen in these intermediates. A method was developed to separate and quantitate by mass (for DG) or endogenous labeling (for PA and PI) the different molecular species of each lipid that are defined by their component fatty acids. The resultant molecular species fingerprint for each lipid was examined to see if it was similar to other intermediates in the PI cycle. For each class of compounds the percent in a given subclass was recorded. Stimulation caused a reduction of more saturated subclasses and/or an increase in AA containing compounds in PA, PI and DG. The relative similarity of subclasses of /sup 32/P-PA and /sup 32/P-PI supports the view that they are metabolically related. The relative absence of AA-containing species of DG suggests that most of the stimulated increase of DG was not produced by PI hydrolysis.

  19. Effects of nerve growth factor antagonist K252a on peritoneal mast cell degranulation: implications for rat postoperative ileus.

    PubMed

    Berdún, Sergio; Rychter, Jakub; Vergara, Patri

    2015-11-15

    Stabilization of mast cell (MC) degranulation has been proposed to prevent postoperative ileus (POI). Nerve growth factor (NGF) mediates MC degranulation. The aim of the study was to evaluate whether NGF receptor antagonist K252a acts as a MC stabilizer in vitro and in vivo model of POI. Peritoneal mast cells (PMCs) were obtained from Sprague-Dawley rats and were incubated with K252a and exposed to NGF or Compound 48/80 (C48/80). MC degranulation was assessed by β-hexosaminidase assay. POI was induced in rats by intestinal manipulation (IM). Rats were pretreated with K252a (100 μg/kg sc) 20 min prior to POI induction. At 20 min after IM, release of rat mast cell protease 6 (RMCP-6) was evaluated in peritoneal lavage. At 24 h, intestinal transit (IT) and gastric emptying (GE) were evaluated. Ileal inflammation was assessed by myeloperoxidase (MPO) activity, expression of IL-6, NGF, TrkA, RMCP-2 and 6, and MC density within the full-thickness ileum. C48/80 and NGF evoked degranulation of PMCs in a dose-dependent manner. K252a prevented NGF-evoked, but not C48/80-evoked, MC degranulation. IM evoked the release of peritoneal RMCP-6 and subsequently delayed IT and GE. IM increased MPO activity and expression of IL-6. In IM rats, K252a prevented upregulation of IL-6 expression and reduced TrkA. IT, GE, and inflammation were not affected by K252a. K252a inhibited NGF-evoked degranulation of PMCs in vitro. In vivo, K252a decreased IL-6 and PMC degranulation. This may be of relevance for the development of new therapeutic targets for POI. PMID:26405114

  20. Human and rat mast cell high-affinity immunoglobulin E receptors: Characterization of putative. alpha. -chain gene products

    SciTech Connect

    Shimizu, Akira; Benfey, P.N.; Leder, P. ); Tepler, I. Brigham and Women's Hospital, Boston, MA ); Berenstein, E.H.; Siraganian, R.P. )

    1988-03-01

    The authors have cloned and determined the entire nucleotide sequence of cDNAs corresponding to the putative {alpha} subunits of the human and rat mast cell high-affinity IgE receptors. Both human and rat cDNAs encode an NH{sub 2}-terminal signal peptide, two immunoglobulin-like extracellular domains (encoded by discrete exons), a hydrophobic transmembrane region, and a positively charged cytoplasmic tail. The human and rat {alpha} subunits share an overall homology with one another and the immunoglobulin gene family, suggesting that they arose from a common ancestral gene and continue to share structural homology with their ligands. In addition, the rat gene is transcribed into at least three distinct forms, each of which yields a somewhat different coding sequence.

  1. Evaluation of the contribution of mast cell mediators to the hypotensive activity of various peptides in rats.

    PubMed

    Kérouac, R; Fournier, A; Barabé, J; St-Pierre, S; Rioux, F

    1983-04-01

    We have tested the effects of intravenous injections of substance P (SP), bradykinin (BK), somatostatin (SS) and vasoactive intestinal peptide (VIP) on the blood pressure, histaminemia and hematocrit in pentobarbital-anesthetized rats. The four peptides elicited a decrease of the mean arterial blood pressure which varied both in amplitude and in duration depending both on the peptide and on the doses utilized. The hypotensive effects of SP and VIP were more persistent than those caused by BK or SS. Only SP evoked an increase of histaminemia. Both SP and BK caused an increase of hematocrit. The change of hematocrit was more prominent and of longer duration after Sp than after BK. Pretreatment of rats with the antiinflammatory drug dexamethasone inhibited markedly the changes of blood pressure, histaminemia and hematocrit caused by SP. The hypotensive effects of BK, SS and VIP as well as the transient change of hematocrit evoked by BK were not affected by dexamethasone. The results suggest that part of the hypotensive activity and changes of hematocrit evoked by SP in rats is due to the release and action of histamine and possibly of other vasoactive substances, of mast cell origin. The results also indicate that mast cell mediators, particularly histamine, are unlikely to be instrumental in the hypotensive activity of BK, SS or VIP in rats.

  2. Brain histaminergic system in mast cell-deficient (Ws/Ws) rats: histamine content, histidine decarboxylase activity, and effects of (S) alpha-fluoromethylhistidine.

    PubMed

    Sugimoto, K; Maeyama, K; Alam, K; Sakurai, E; Onoue, H; Kasugai, T; Kitamura, Y; Watanabe, T

    1995-08-01

    The mast cell-deficient [Ws/Ws (White spotting in the skin)] rat was investigated with regard to the origin of histamine in the brain. No mast cells were detected in the pia mater and the perivascular region of the thalamus of Ws/Ws rats by Alcian Blue staining. The histamine contents and histidine decarboxylase (HDC) activities of various brain regions of Ws/Ws rats were similar to those of +/+ rats except the histamine contents of the cerebral cortex and cerebellum. As the cerebral cortex and cerebellum have meninges that are difficult to remove completely, the histamine contents of these two regions may be different between Ws/Ws and +/+ rats. We assume that the histamine content of whole brain with meninges in Ws/Ws rats is < 60% of that in +/+ rats. So we conclude that approximately half of the histamine content of rat brain is derived from mast cells. Next, the effects of (S) alpha-fluoromethylhistidine (FMH), a specific inhibitor of HDC, on the histamine contents and HDC activities of various regions of the brain were examined in Ws/Ws rats. In the whole brain of Ws/Ws rats, 51 and 37% of the histamine content of the control group remained 2 and 6 h, respectively, after FMH administration (100 mg/kg of body weight). Therefore, we suggest that there might be other histamine pools including histaminergic neurons in rat brain.

  3. Role of mast cells in wound healing process after glass - fiber composite implant in rats

    PubMed Central

    Rodella, L F; Rezzani, Rita; Buffoli, Barbara; Bonomini, Francesca; Tengattini, Sandra; Laffranchi, Laura; Paganelli, C; Sapelli, P L; Bianchi, Rossella

    2006-01-01

    Glass-fiber composites are frequently used in dentistry. In order to evaluate their biocompatibility we tested, in an experimental model “in vivo”, their tissue response pointing our attention on presence of mast cells (MCs) and fibrotic process. Sprague Dawley rats were used for the experimental design. The fibers were introduced in a subcutaneous pocket along the middle dorsal line between the two scapulas for 7, 14 or 21 days. At the end of the treatments the skins were excised and then processed for Toluidine Blue, to determine the presence of MCs, and Picrosirius Red staining, to evaluate the presence of fibrotic tissue. Our preliminary results showed and increase of both MC number and deposition of collagen type I, which characterized the fibrotic tissue. So, subsequent aims of our study were to evaluate the role played by MCs in tissue fibrosis and to give a possible explanation regarding the mechanisms that were responsible of biological response observed, through the analyses of some proteins, such as metalloproteinase-2 (MMP-2), its inhibitor (TIMP-2) and transforming growth factor-β (TGF-β). Our data confirmed the involvement of TGF-β, released by MCs, in the disruption of the equilibrium between MMP-2 and TIMP-2 that were implicated in the enhancement of fibrosis. In summary, this study demonstrate that this type of materials induced an inflammatory response at the site of implant and help to clarify what type of mechanism and which proteins are involved in this biological response. Nevertheless, more extensive investigations are in progress to better evaluate the inflammatory process. PMID:17125597

  4. Analysis of the effect of a 60 Hz AC field on histamine release by rat peritoneal mast cells.

    PubMed

    Price, J A; Strattan, R D

    1998-01-01

    Reports have indicated effects of electromagnetic fields on inflammatory processes in vivo. To begin a systematic approach toward separating and examining the many components of such responses, we created and tested a temperature-controlled device to develop 5 mT 60 Hz magnetic fields for studies of the effects of fields on mast cells, a key component in acute inflammatory responses. Such fields have been reported to modulate cell activity, including changes in membrane function, in various systems. The magnetic field was generated using a solenoid and calibrated with an induction probe. Tests of mast cell function were determined by histamine release response to stimulation by compound 48/80, using both an "expose then test" and a "test during exposure" protocol. Aliquots not treated with 48/80 were used to evaluate field treatment effects on spontaneous histamine release. Freshly harvested rat peritoneal mast cells were exposed to the magnetic field for periods of 30 min to 2 h at 37 degrees C. They showed no significant degranulation during treatment, nor did they show reduced sensitivity to the degranulating agent 48/80. These observations are consistent with a model in which such processes are exclusively reflexive by the cells using field-independent membrane systems. This observation is very useful and was needed before examining longer term exposures in which gene expression in the cells might be influenced; this is the first such report of in vitro exposure of purified mast cells under these conditions and will further the study of the effects of electromagnetic fields on cell types active in acute inflammation.

  5. Intestinal mast cells and eosinophils in relation to Strongyloides ratti adult expulsion from the small and large intestines of rats.

    PubMed

    Shintoku, Y; Kadosaka, T; Kimura, E; Takagi, H; Kondo, S; Itoh, M

    2013-04-01

    Mucosal mast cells (MMC) play a crucial role in the expulsion of Strongyloides ratti adults from the small intestine of mice. We reported the large intestinal parasitism of S. ratti in rats, and there has been no report on MMC in the large intestine of the natural host. We studied kinetics of MMC, together with eosinophils, in the upper and lower small intestines, caecum and colon of infected rats. Two distinct phases of mastocytosis were revealed: one in the upper small intestine triggered by stimulation of 'ordinary' adults, and the other in the colon stimulated by 'immune-resistant' adults that started parasitizing the colon around 19 days post-infection. In all 4 intestinal sites, the MMC peaks were observed 5-7 days after the number of adult worms became the maximum and the height of MMC peaks appeared to be dependent on the number of parasitic adults, suggesting an important role played by worms themselves in the MMC buildup.

  6. Synthesis of ε-Viniferin Glycosides by Glucosyltransferase from Phytolacca americana and their Inhibitory Activity on Histamine Release from Rat Peritoneal Mast Cells.

    PubMed

    Hamada, Hiroki; Hamada, Hatsuyuki; Shimoda, Kei

    2015-06-01

    Glycosylation of (+)-ε-viniferin was investigated using glucosyltransferase from Phytolacca americana (PaGT3) as a biocatalyst. (+)-ε-Viniferin was converted by PaGT3 into its 4b- and 13b-β-D-glucosides, the inhibitory activities on histamine release from rat peritoneal mast cells of which were higher than that of (+)-ε-viniferin.

  7. Role of the Na+/K+-ATPase in regulating the membrane potential in rat peritoneal mast cells.

    PubMed

    Friis, U G; Praetorius, H A; Knudsen, T; Johansen, T

    1997-10-01

    1. The aim of this study was to investigate the effect of the Na+/K+-ATPase on the membrane potential of peritoneal mast cells isolated from male Sprague-Dawley SPF-rats. 2. Experiments were performed at 22-26 degrees C in the tight-seal whole-cell configuration of the patch-clamp technique by use of Sylgard-coated patch pipettes (3-6 M[omega]). High-resolution membrane currents were recorded with an EPC-9 patch-clamp amplifier controlled by the 'E9SCREEN' software. In addition, a charting programme on another computer synchronously recorded at low resolution (2 Hz) membrane potential and holding current (low-pass filtered at 500 Hz). 3. Na+/K+-ATPase activity was measured as the ouabain-sensitive change in the zero-current potential. The zero-current potential in rat peritoneal mast cells measured 2 min after obtaining whole-cell configuration amounted to 1.7 +/- 2.5 mV (n = 21). Ouabain (5 mM), a Na+/K+-ATPase-inhibitor, had only a very minor effect upon the membrane potential under resting conditions (n = 3). 4. When mast cells were superfused with nominal calcium-free external solution, the cells hyperpolarized (delta mV: 20.2 +/- 3.8 mV (n = 5)). In addition, when the mast cells were preincubated in nominal calcium-free external solution for 12 +/- 1.6 min before whole-cell configuration, the membrane potential amounted to -53.7 +/- 9.8 mV (n = 8). A subsequent superfusion with ouabain (5 mM) depolarized the membrane potential (ouabain-sensitive hyperpolarization (delta mV): 23.0 +/- 8.4 mV (n = 8)). 5. A high intracellular concentration of Na+ ([Na+]i) (26.6 mM) also resulted in hyperpolarization (delta mV: 20.2 +/- 9.1 mV (n = 7)), but only when ATP was present. A subsequent superfusion with ouabain (5 mM) repolarized these cells to -1.2 +/- 14 mV (ouabain-sensitive hyperpolarization (delta mV): 19.7 +/- 7.7 mV (n = 7)). 6. The size of the [Na+]i-dependent hyperpolarization was dose-dependent. Low [Na+]i (1 mM) had no effect on membrane potential and these

  8. Repeated Water Avoidance Stress Alters Mucosal Mast Cell Counts, Interleukin-1β Levels with Sex Differences in the Distal Colon of Wistar Rats

    PubMed Central

    Lee, Ju Yup; Kim, Nayoung; Kim, Yong Sung; Nam, Ryoung Hee; Ham, Min Hee; Lee, Hye Seung; Jo, Wonjun; Shim, Youngkwang; Choi, Yoon Jin; Yoon, Hyuk; Shin, Cheol Min; Lee, Dong Ho

    2016-01-01

    Background/Aims This study was aimed at evaluating differences in the effects of repeated water avoidance stress (rWAS) on colonic movement, mucosal mast cell counts, cytokine levels, and visceromotor response (VMR) to colorectal distension (CRD) in rats of both sexes. Methods Wistar rats were divided into stress and no-stress groups. Rats in the stress group were exposed to rWAS (1 hr/day) for 10 days. Mucosal mast cells were immunohistochemically stained with anti-mast cell tryptase antibody and counted. The colonic mucosal cytokine levels were measured with enzyme-linked immunosorbent assay. The VMR to CRD (visceral analgesia) was assessed by using a barostat and noninvasive manometry. Results The mean number of fecal pellets in the rWAS group increased significantly as compared with that in the no-stress group in both sexes. After adjustment for body weight, the female rats had a significantly higher pellet output than the male rats. The mucosal mast cell count of the female rWAS group was higher than that of the male rWAS group (13.0 ± 0.9 vs 8.8 ± 0.6; P < 0.001). The colonic mucosal interleukin-1β level was also higher only in the female rats of the rWAS group than in those of the no-stress group. On days 10 and 11, a decrease in VMR to CRD was observed at 40 and 60 mmHg in both sexes of the rWAS group, without a sex-based difference. Conclusions The colonic response to stress appeared to be more sensitive in the female rats than in the male rats. However, stress-induced visceral analgesia had no sex-related difference and the underlying mechanism needs to be further evaluated. PMID:27466288

  9. Chronic ingestion of a potential food contaminant induces gastrointestinal inflammation in rats: role of nitric oxide and mast cells.

    PubMed

    Anton, P M; Theodorou, V; Bertrand, V; Eutamene, H; Aussenac, T; Feyt, N; Fioramonti, J; Bueno, L

    2000-09-01

    Chronic ingestion of xenobiotics could be pathogenic in the gastrointestinal tract. Recently, we showed that acute low administration of a food contaminant (diquat) induced intestinal secretion involving mast cells and nitric oxide. This work aimed to determine in rats: (1) the influence of a low level (0.1 mg/kg/day per os) chronic ingestion of diquat on gastrointestinal immune cells, and (2) the participation of nitric oxide synthases (NOS) in these effects. Diquat increased both gastric and jejunal myeloperoxidase activities, tissue histamine in vitro release after stimulation by 48/80, and mast cell numbers. Diquat did not alter gastric NOS but increased intestinal inducible NOS (iNOS) activity. L-NAME prevented diquat-induced gastric and intestinal mastocytosis and gastric but not intestinal inflammation. L-NAME reduced gastric constitutive NOS (cNOS) activity and reestablished control iNOS activity. Chronic low level ingestion of diquat induces a low-grade gastric and intestinal inflammation with mastocytosis and enhancement of intestinal iNOS activity.

  10. The effects of thermal stimuli on intracellular calcium change and histamine releases in rat basophilic leukemia mast cells

    NASA Astrophysics Data System (ADS)

    Wu, Zu-Hui; Zhu, Dan; Chen, Ji-Yao; Zhou, Lu-Wei

    2012-05-01

    The effects of thermal stimuli on rat basophilic leukemia mast cells were studied. The cells in calcium-contained or calcium-free buffers were thermally stimulated in the temperature range of 25-60 °C. The corresponding calcium ion concentration in cells [Ca2+]i as well as the released histamine from cells was measured with fluorescence staining methods. The ruthenium red (RR), a block of membrane calcium channels (transient receptor potential family V (TRPV)), was used in experiments. Under the stimulus of 25-50 °C, no significant difference on [Ca2+]i was found between these three groups of the cells in calcium-contained buffer without or with RR and cells in calcium-free saline, indicating that the increased calcium in cytosol did not result from the extracellular buffer but came from the intracellular calcium stores. The [Ca2+]i continuously increased under the temperature of 50-60 °C, but the RR and calcium-free saline can obviously diminish the [Ca2+]i increase at these high temperatures, reflecting that the opening of the TRPV2 channels leads to a calcium influx resulting in the [Ca2+]i increment. The histamine release also became significant in these cases. Since the released histamine is a well-known mediator for the microcirculation promotion, the histamine release from mast cells could be one of the mechanisms of thermal therapy.

  11. Characteristics of histamine release from rat mast cells in relation to the valency of the stimulating ligand.

    PubMed Central

    Healicon, R M; Foreman, J C

    1986-01-01

    The relationship between the valency of a ligand and the subsequent characteristics of histamine release was investigated in rat peritoneal mast cells. The cells were passively sensitized to the DNP hapten and a series of DNP-human serum albumin conjugates of known valency were used to induce histamine release. The rate of release of histamine induced by these conjugates was independent of the DNP/HSA ratio when the ratio was between 71.3 and 7.2. Marked slowing of the release occurred as the ratio was reduced below 7.2. The rate of desensitization of the cells slowed as a continuous function as the DNP/HSA ratio was reduced. 45Calcium uptake measurements showed that the changes in histamine release were paralleled by changes in the membrane permeability to calcium. The rate of release of histamine from mast cells and the rate of desensitization of the cells are discussed in terms of the size of IgE receptor complexes on the cell membrane. PMID:2420710

  12. Effects of melanin-induced free radicals on the isolated rat peritoneal mast cells

    SciTech Connect

    Ranadive, N.S.; Shirwadkar, S.; Persad, S.; Menon, I.A.

    1986-03-01

    Pheomelanin from human red hair (RHM) produces considerably more cellular damage in Ehrlich ascites carcinoma cells when subjected to radiations of wavelength 320-700 nm than eumelanin from black hair (BHM). Irradiation of RHM generated large amounts of superoxide while BHM did not produce detectable amounts of superoxide. The present investigations describe the effects of irradiation of mast cells in the presence of various natural and synthetic melanins. Irradiation of mast cells in the presence of RHM and red hair melanoprotein released large amounts of histamine while BHM and synthetic melanins prepared from dopa, cysteinyldopa, or a mixture of dopa and cysteinyldopa did not release histamine. The release of histamine at lower concentrations of RHM was not accompanied by the release of /sup 51/Cr from chromium-loaded cells, suggesting that this release was of noncytotoxic nature. On the other hand, the release of histamine at higher concentrations of RHM was due to cell lysis since both histamine and cytoplasmic marker /sup 51/Cr were released to the same extent. The release evoked by large concentration RHM was not inhibited by superoxide dismutase or catalase. This suggests that the cell lysis under these conditions was not due to H/sub 2/O/sub 2/ or O-2. The finding that mast cells release histamine when irradiated in the presence of RHM suggests that the immediate and late-phase reactions seen in sunburn may in part be due to the release of mediators from these cells.

  13. Identification of oversulphated galactosaminoglycans in intestinal-mucosal mast cells of rats infected with the nematode worm Nippostrongylus brasiliensis.

    PubMed Central

    Kusche, M; Lindahl, U; Enerbäck, L; Rodén, L

    1988-01-01

    The oversulphated galactosaminoglycans synthesized by rat mucosal mast cells were isolated from the small intestine of animals infected with the nematode Nippostrongylus brasiliensis, which causes proliferation of these cells. The 35S-labelled polysaccharides were degraded by digestion with chondroitinase ABC, and the structures of the disaccharide products were determined by cleavage with mercuric acetate followed by electrophoretic characterization of the resultant sulphated monosaccharides. It was concluded that about half of the disulphated disaccharide units in the polysaccharide consisted of chondroitin sulphate E-type structures [GlcA-GalNAc(4,6-di-OSO3)], in which both sulphate groups were located on the N-acetylgalactosamine unit. The remainder consisted of isomeric structures with one sulphate group on the N-acetylgalactosamine residue and one on the hexuronic acid unit and presumably represented the dermatan sulphate-type sequence [IdoA(2-OSO3)-GalNAc(4-OSO3)]. PMID:3178741

  14. Evidence for lipoxygenase activity in induction of histamine release from rat peritoneal mast cells by chelated iron.

    PubMed Central

    Magro, A M; Brai, M

    1983-01-01

    The ferric iron-desferrioxamine B chelate effectively induced histamine release from rat peritoneal mast cells. The release was maximum at exogenous ferric iron concentrations of 10-100 microM, and the chelate was non-toxic, as determined by trypan blue uptake. In many aspects the chelate-induced histamine release paralleled IgE-mediated release. The kinetics, temperature, and Ca2+ dependence resembled antigen-induced release. Phosphatidylserine potentiated the release in Wistar rats but not in fawn-hooded rats, a strain which does not respond to phosphatidylserine potentiation. The chelate-induced histamine release was blocked by the metabolic inhibitors dinitrophenol, potassium cyanide, 2-deoxyglucose, and antimycin A. Lipoxygenase inhibitors also effectively blocked release, indicating an involvement of fatty acid metabolism via the lipoxygenase pathway. Free radical scavengers and antioxidants antagonistic to lipid peroxidation also inhibited the chelate-induced histamine release. Overall the data raise the possibility that endogenous cellular iron may be involved in the generation of free radicals and lipid peroxidation and that these may be early events in IgE-mediated release of histamine. PMID:6188682

  15. Structure-activity relationship of a series of 17 parabens and related compounds for histamine release in rat peritoneal mast cells and skin allergic reaction in guinea pigs.

    PubMed

    Uramaru, Naoto; Inoue, Toshio; Watanabe, Yoko; Shigematsu, Hidenari; Ohta, Shigeru; Kitamura, Shigeyuki

    2014-02-01

    Parabens, which are a homologous series of esters of p-hydroxybenzoic acid, have been used as preservatives in cosmetics, medicines and foods because of their antimicrobial activity. However, parabens in cosmetics have been suspected to cause allergic contact dermatitis. In this study, we examined paraben-induced histamine release from rat peritoneal mast cells and skin reaction in guinea pigs using a series of 17 parabens with different alcohol side chains, ranging from methylparaben to dodecylparaben. Octylparaben showed the greatest histamine release-inducing activity from mast cells, and the activity was decreased in shorter- and longer-side-chain parabens. Octyl benzoate, octyl o-hydroxybenzoate and phenyloctane caused no significant degranulation of mast cells, whereas octyl m-hydroxybenzoate, octyl p-hydroxybenzoate and octyl phenol induced concentration-related degranulation. Metabolites of these parabens (p-hydroxybenzoic acid and alcohols) did not show histamine release-inducing activity. In the guinea pig skin reaction test, heptylparaben induced a typical strong skin reaction, while butylparaben induced a typical weak skin reaction, and methylparaben and dodecylparaben were inactive. Metabolites of parabens (p-hydroxybenzoic acid and alcohols) were also inactive. These results indicate that interaction of parabens with rat mast cells requires a minimum length and adequate lipophilicity of the alkyl side chain. Since metabolites of parabens were inactive, parabens appear to be direct-acting allergens.

  16. The Effects of Electrical Stimuli on Calcium Change and Histamine Release in Rat Basophilic Leukemia Mast Cells

    NASA Astrophysics Data System (ADS)

    Zhu, Dan; Wu, Zu-Hui; Chen, Ji-Yao; Zhou, Lu-Wei

    2013-06-01

    We apply electric fields at different frequencies of 0.1, 1, 10 and 100 kHz to the rat basophilic leukemia (RBL) mast cells in calcium-containing or calcium-free buffers. The stimuli cause changes of the intracellular calcium ion concentration [Ca2+]i as well as the histamine. The [Ca2+]i increases when the frequency of the external electric field increases from 100 Hz to 10 kHz, and then decreases when the frequency further increases from 10 kHz to 100 kHz, showing a peak at 100 kHz. A similar frequency dependence of the histamine release is also found. The [Ca2+]i and the histamine releases at 100 Hz are about the same as the values of the control group with no electrical stimulation. The ruthenium red (RR), an inhibitor to the TRPV (transient receptor potential (TRP) family V) channels across the cell membrane, is used in the experiment to check whether the electric field stimuli act on the TRPV channels. Under an electric field of 10 kHz, the [Ca2+]i in a calcium-concentration buffer is about 3.5 times as much as that of the control group with no electric stimulation, while the [Ca2+]i in a calcium-free buffer is only about 2.2 times. Similar behavior is also found for the histamine release. RR blockage effect on the [Ca2+]i decrease is statistically significant (~75%) when mast cells in the buffer with calcium are stimulated with a 10 kHz electric field in comparison with the result without the RR treatment. This proves that TRPVs are the channels that calcium ions inflow through from the extracellular environment under electrical stimuli. Under this condition, the histamine is also released following a similar way. We suggest that, as far as an electric stimulation is concerned, an application of ac electric field of 10 kHz is better than other frequencies to open TRPV channels in mast cells, and this would cause a significant calcium influx resulting in a significant histamine release, which could be one of the mechanisms for electric therapy.

  17. Dectin-1-mediated Signaling Leads to Characteristic Gene Expressions and Cytokine Secretion via Spleen Tyrosine Kinase (Syk) in Rat Mast Cells*

    PubMed Central

    Kimura, Yukihiro; Chihara, Kazuyasu; Honjoh, Chisato; Takeuchi, Kenji; Yamauchi, Shota; Yoshiki, Hatsumi; Fujieda, Shigeharu; Sada, Kiyonao

    2014-01-01

    Dectin-1 recognizes β-glucan and plays important roles for the antifungal immunity through the activation of spleen tyrosine kinase (Syk) in dendritic cells or macrophages. Recently, expression of Dectin-1 was also identified in human and mouse mast cells, although its physiological roles were largely unknown. In this report, rat mast cell line RBL-2H3 was analyzed to investigate the molecular mechanism of Dectin-1-mediated activation and responses of mast cells. Treatment of cells with Dectin-1-specific agonist curdlan induced tyrosine phosphorylation of cellular proteins and the interaction of Dectin-1 with the Src homology 2 domain of Syk. These responses depended on tyrosine phosphorylation of the hemi-immunoreceptor tyrosine-based activation motif in the cytoplasmic tail of Dectin-1, whereas they were independent of the γ-subunit of high-affinity IgE receptor. DNA microarray and real-time PCR analyses showed that Dectin-1-mediated signaling stimulated gene expression of transcription factor Nfkbiz and inflammatory cytokines, such as monocyte chemoattractant protein-1, IL-3, IL-4, IL-13, and tumor necrosis factor (TNF)-α. The response was abrogated by pretreatment with Syk inhibitor R406. These results suggest that Syk is critical for Dectin-1-mediated activation of mast cells, although the signaling differs from that triggered by FcϵRI activation. In addition, these gene expressions induced by curdlan stimulation were specifically observed in mast cells, suggesting that Dectin-1-mediated signaling of mast cells offers new insight into the antifungal immunity. PMID:25246527

  18. A central role for the mast cell in early phase vasculitis in the Brown Norway rat model of vasculitis: a histological study

    PubMed Central

    Vinen, Catherine S; Turner, David R; Oliveira, David B G

    2004-01-01

    Administration of mercuric chloride (HgCl2) to Brown Norway rats causes Th2-dominated autoimmunity with raised immunoglobulin E concentrations and gut vasculitis, both of which are T-cell dependent, peak at 14 days after starting HgCl2 and then spontaneously resolve. If animals are re-challenged with HgCl2 6 weeks after initial exposure, they are resistant to autoimmunity, developing only attenuated disease. Recently, a separate phase of early caecal vasculitis was described beginning 24 h after initiating HgCl2 and prior to caecal entry of T cells. Previous work suggested this early vasculitis was αβ T-cell independent and implied a role for mast cells. We further tested this hypothesis by performing a histological study during the first 93 h following HgCl2 challenge defining the precise relationship between gut mast cell degranulation and appearing caecal vasculitis. We also studied whether early caecal vasculitis enters a resistant phase upon re-challenge with HgCl2. We show a direct correlation between mast cell degranulation and early caecal vasculitis following initial HgCl2 challenge. We demonstrate resistance to re-challenge in this phase of injury, with results at re-challenge also showing a correlation between mast cell degranulation and early caecal injury. PMID:15255970

  19. Number Density of Mast Cells in the Primo Nodes of Rats.

    PubMed

    Gil, HyunJi; Bae, Kyoung-Hee; Kim, LiJung; Kim, SungChul; Soh, Kwang-Sup

    2015-12-01

    Mast cells (MCs) play a major role in allergic reactions. Surprisingly, the acupuncture points have a higher density of MCs compared with nonacupoints in the skin, which is consistent with the augmentation of the immune function by acupuncture treatment. We hypothesized that the primo vascular system (PVS), which was proposed as the anatomical structure of the acupuncture points and meridians, should have a high density of MCs. In order to test that hypothesis, we investigated the primo nodes isolated from the surfaces of internal organs, such as the liver, the small and the large intestines, and the bladder. The harvested primo nodes were stained with toluidine blue, and the MCs were easily recognized by their red-purple stains and their characteristic granules. The results showed a high density of MCs in the primo nodes and confirmed the hypothesis. The MCs were uniformly distributed in the nodes. The relative concentration of the MCs with respect to other cells was ∼15%. We divided the sizes of the primo nodes into three classes: large, medium, and small. The number density and the relative concentration of MCs did not show a size-dependence. The current work suggests that the PVS may participate in the immune response to allergic inflammation, which closely involves MCs.

  20. The effects of a chactoid scorpion venom and its purified toxins on rat blood pressure and mast cells histamine release.

    PubMed

    Ettinger, Keren; Cohen, Gadi; Momic, Tatjana; Lazarovici, Philip

    2013-07-29

    The effect of the venom of the Chactoid family of scorpions on blood pressure was scantly investigated and was addressed in the present study using the venom of the Israeli scorpion, Scorpio maurus palmatus. Blood pressure in rats was monitored via cannulated femoral artery, while venom and toxins were introduced into femoral vein. Venom injection elicited a biphasic effect, expressed first by a fast and transient hypotensive response, which lasted up to 10 min, followed by a hypertensive response, which lasted up to one hour. It was found that these effects resulted from different venom components. Phospholipase A₂ produced the hypotensive effect, while a non-enzymatic neurotoxic polypeptide fraction produced the hypertensive effect. Surprisingly, the main neurotoxic polypeptide to mice had no effect on blood pressure. In vitro experiments indicated that the hypertensive factors caused histamine release from the peritoneal mast cells, but this effect is assumed to be not relevant to their in vivo effect. In spite of the cytotoxic activity of phospholipase A₂, it did not release histamine. These findings suggest that the effects of venom and isolated fractions on blood pressure parameters are mediated by different mechanisms, which deserve further pharmacological investigation.

  1. Evidence for a role of phosphatidylinositol turnover in stimulus–secretion coupling. Studies with rat peritoneal mast cells

    PubMed Central

    Cockcroft, Shamshad; Gomperts, Bastien D.

    1979-01-01

    Histamine secretion and phosphatidylinositol turnover were compared in antigen-sensitized rat peritoneal mast cells stimulated with a number of different ligands. A small and variable increase in the incorporation of [32P]Pi and of [3H]inositol into phosphatidylinositol was observed when the cells were treated with immunoglobulin E-directed ligands (antigens and concanavalin A), and this was accompanied by a low amount of secretion (<10% of total cell histamine). In the presence of added phosphatidylserine, the addition of immunoglobulin E-directed ligands invariably led to an enhanced rate (approx. 4-fold) of labelling of phosphatidylinositol and, in the presence of Ca2+, this was accompanied by the secretion of histamine. The labelling of phosphatidylinositol and histamine secretion were also stimulated by chymotrypsin and compound 48/80. Whereas the phosphatidylinositol response did not require the presence of extracellular Ca2+, the secretion of histamine was either enhanced or dependent on extracellular Ca2+ (depending on the ligand used). The dependence on ligand concentration for the phosphatidylinositol response and histamine secretion were similar. The increased isotopic incorporation into phosphatidylinositol continued for about 1h although histamine secretion (elicited with concanavalin A) stopped within 2min. These results support the proposition that metabolic events involving phosphatidylinositol play a necessary intermediate role in the regulation of Ca2+ channels by ligand-activated receptors. PMID:88219

  2. Sex-related differences in mast cell activity and doxorubicin toxicity: a study in spontaneously hypertensive rats.

    PubMed

    Zhang, Jun; Knapton, Alan; Lipshultz, Steven E; Cochran, Thomas R; Hiraragi, Hajime; Herman, Eugene H

    2014-01-01

    Clinically, girls appear to be more sensitive than boys to the cardiotoxic effects of doxorubicin, whereas the opposite may be true for adults. To identify and characterize potential sex-related differences, adult male and female spontaneously hypertensive rats (SHR; some ovariectomized [OVX]) received 1 mg/kg of doxorubicin or saline iv weekly for 9, 10, or 12 weeks. Weight gain was slower in treated males. Serum concentrations of cholesterol and triglycerides increased and those of albumin decreased in both sexes, but changes were more pronounced in treated males. Treated males had significantly more severe cardiomyopathy scores and higher serum levels of cTnT than females. The increased cardiotoxicity was accompanied by higher numbers of cardiac mast cells (MCs) and percentage of cardiac MCs undergoing degranulation. Doxorubicin-treated OVX animals had significantly increased numbers of cardiac MCs, more severe myocardial lesions, and elevated serum concentrations of cTnT compared to doxorubicin-treated normal female SHR. The severity of cardiac lesions in the OVX female was similar to that observed in doxorubicin-treated males. This study demonstrated the presence of sex-related differences in the cardiotoxic effects elicited by doxorubicin and identified variations in the level of cardiac MC activity as a factor which could possibly contribute to the male-female dissimilarity.

  3. Regulation of rat basophilic leukemia-2H3 mast cell secretion by a constitutive Lyn kinase interaction with the high affinity IgE receptor (Fc epsilon RI).

    PubMed

    Vonakis, Becky M; Gibbons, Scott P; Rotté, Masashi J; Brothers, Elizabeth A; Kim, Seok C; Chichester, Kristin; MacDonald, Susan M

    2005-10-01

    Signaling through the high affinity IgE receptor is initiated by noncovalently associated Lyn kinase, resulting in the secretion of inflammatory mediators from mast cells. A fraction of the total cellular Lyn is associated via its N-terminal unique domain with the cytoplasmic domain of the Fc epsilonRI beta subunit before receptor aggregation. In the current study, we stably transfected the unique domain of Lyn into rat basophilic leukemia-2H3 mast cells and examined the consequences on Fc epsilonRI-induced signal transduction and mediator secretion to further define the role of the unique domain of Lyn in mast cell secretion. Tyrosine phosphorylation of Fc epsilonRI beta and gamma subunits was partially inhibited in the Lyn unique domain transfectants after Ag stimulation. Ag stimulation of Lyn unique domain transfectants was accompanied by enhanced phosphorylation of MEK and ERK-2, which are required for leukotriene C4 (LTC4) release, and production of LTC4 was increased 3- to 5-fold, compared with cells transfected with vector alone. Conversely, tyrosine phosphorylation of the adaptor protein Gab2, which is essential for mast cell degranulation, was inhibited after Ag stimulation of Lyn unique domain transfectants, and Ag-induced release of histamine was inhibited up to 48%. In rat basophilic leukemia-2H3 cells, Lyn thus plays a dual role by positively regulating Fc epsilonRI phosphorylation and degranulation while negatively regulating LTC4 production. This study provides further evidence that the constitutive interaction between the unique domain of Lyn and the Fc epsilonRI beta subunit is a crucial step in the initiation of Fc epsilonRI signaling and that Lyn is limiting for Fc epsilonRI-induced secretion of inflammatory mediators.

  4. Progesterone inhibits mast cell secretion.

    PubMed

    Vasiadi, M; Kempuraj, D; Boucher, W; Kalogeromitros, D; Theoharides, T C

    2006-01-01

    Mast cells are involved in allergic reactions, where they secrete numerous vasoactive, inflammatory and nociceptive mediators in response to immunoglobulin E (IgE) and antigen. However, they have also been implicated in inflammatory conditions, such as painful bladder syndrome/interstitial cystitis (PBS/IC), irritable bowel syndrome (IBS) and migraines, all of which occur more often in women and are exacerbated during ovulation, but are suppressed during pregnancy. Mast cells express high affinity estrogen receptors and estradiol augments their secretion, while tamoxifen inhibits it. Here we report that progesterone (100 nM), but not the structurally related cholesterol, inhibits histamine secretion from purified rat peritoneal mast cells stimulated immunologically or by substance P (SP), an effect also documented by electron microscopy. These results suggest that mast cell secretion may be regulated by progesterone and may explain the reduced symptoms of certain inflammatory conditions during pregnancy.

  5. Antimicrobial agent triclosan is a proton ionophore uncoupler of mitochondria in living rat and human mast cells and in primary human keratinocytes.

    PubMed

    Weatherly, Lisa M; Shim, Juyoung; Hashmi, Hina N; Kennedy, Rachel H; Hess, Samuel T; Gosse, Julie A

    2016-06-01

    Triclosan (TCS) is an antimicrobial used widely in hospitals and personal care products, at ~10 mm. Human skin efficiently absorbs TCS. Mast cells are ubiquitous key players both in physiological processes and in disease, including asthma, cancer and autism. We previously showed that non-cytotoxic levels of TCS inhibit degranulation, the release of histamine and other mediators, from rat basophilic leukemia mast cells (RBL-2H3), and in this study, we replicate this finding in human mast cells (HMC-1.2). Our investigation into the molecular mechanisms underlying this effect led to the discovery that TCS disrupts adenosine triphosphate (ATP) production in RBL-2H3 cells in glucose-free, galactose-containing media (95% confidence interval EC50 = 7.5-9.7 µm), without causing cytotoxicity. Using these same glucose-free conditions, 15 µm TCS dampens RBL-2H3 degranulation by 40%. The same ATP disruption was found with human HMC-1.2 cells (EC50 4.2-13.7 µm), NIH-3 T3 mouse fibroblasts (EC50 4.8-7.4 µm) and primary human keratinocytes (EC50 3.0-4.1 µm) all with no cytotoxicity. TCS increases oxygen consumption rate in RBL-2H3 cells. Known mitochondrial uncouplers (e.g., carbonyl cyanide 3-chlorophenylhydrazone) previously were found to inhibit mast cell function. TCS-methyl, which has a methyl group in place of the TCS ionizable proton, affects neither degranulation nor ATP production at non-cytotoxic doses. Thus, the effects of TCS on mast cell function are due to its proton ionophore structure. In addition, 5 µm TCS inhibits thapsigargin-stimulated degranulation of RBL-2H3 cells: further evidence that TCS disrupts mast cell signaling. Our data indicate that TCS is a mitochondrial uncoupler, and TCS may affect numerous cell types and functions via this mechanism. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26204821

  6. Effects of methyl p-hydroxybenzoate (methyl paraben) on Ca2+ concentration and histamine release in rat peritoneal mast cells

    PubMed Central

    Fukugasako, Sanae; Ito, Shinichi; Ikemoto, Yoshimi

    2003-01-01

    Mechanisms of methyl p-hydroxybenzoate (methyl paraben) action in allergic reactions were investigated by measuring the intracellular Ca2+ concentration ([Ca2+]i) and histamine release in rat peritoneal mast cells (RPMCs). In the presence or absence of extracellular Ca2+, methyl paraben (0.1–10 mM) increased [Ca2+]i, in a concentration-dependent manner. Under both the conditions, methyl paraben alone did not evoke histamine release. In RPMCs pretreated with a protein kinase C (PKC) activator (phorbol 12-myristate 13-acetate (PMA) 3 and 10 nM), methyl paraben (0.3–3 mM) induced histamine release. However, a high concentration (10 mM) of the agent did not increase the histamine release. U73122 (0.1 and 0.5 μM), an inhibitor of phospholipase C (PLC), significantly inhibited the methyl paraben-induced histamine release in PMA-pretreated RPMCs. U73343 (0.5 μM), an inactive analogue of U73122, did not inhibit the histamine release caused by methyl paraben. In Ca2+-free solution, PLC inhibitors (U73122 0.1 and 0.5 μM, D609 1–10 μM) inhibited the methyl paraben-induced increase in [Ca2+]i, whereas U73343 (0.5 μM) did not. Xestospongin C (2–20 μM) and 2 aminoethoxydiphenyl borate (30 and 100 μM), blockers of the inositol 1,4,5-trisphosphate (IP3) receptor, inhibited the methyl paraben-induced increase in [Ca2+]i in Ca2+-free solution. In conclusion, methyl paraben causes an increase in [Ca2+]i, which may be due to release of Ca2+ from storage sites by IP3 via activation of PLC in RPMCs. In addition, methyl paraben possibly has some inhibitory effects on histamine release via unknown mechanisms. PMID:12770943

  7. Apoptosis and T-cell depletion during feline infectious peritonitis.

    PubMed

    Haagmans, B L; Egberink, H F; Horzinek, M C

    1996-12-01

    Cats that have succumbed to feline infectious peritonitis, an immune-mediated disease caused by variants of feline coronaviruses, show apoptosis and T-cell depletion in their lymphoid organs. The ascitic fluid that develops in the course of the condition causes apoptosis in vitro but only in activated T cells. Since feline infectious peritonitis virus does not infect T cells, and viral proteins did not inhibit T-cell proliferation, we postulate that soluble mediators released during the infection cause apoptosis and T-cell depletion.

  8. Guanine nucleotide is essential and Ca2+ is a modulator in the exocytotic reaction of permeabilized rat mast cells.

    PubMed Central

    Lillie, T H; Gomperts, B D

    1992-01-01

    Exocytosis from metabolically depleted permeabilized rat mast cells was measured in response to provision of Ca2+ and guanine nucleotide [GTP or guanosine 5'-[gamma-thio]triphosphate (GTP[S])]. For cells permeabilized in simple salt solutions (NaCl), both of these effectors were required to induce secretion. Exclusion of Mg2+ caused an increase in both the sensitivity of the system to GTP and the extent of secretion elicited, while having no such effects on secretion induced by GTP[S]. The effect of Mg2+ depletion on the ability of GTP to stimulate secretion is probably due to the dependence on Mg2+ of the GTPase activity of GE (a postulated GTP-binding protein which mediates exocytosis). This argues that a persistent stimulus to the G-protein is required to support secretion. Affinity for both GTP[S] and GTP is enhanced when the cells are permeabilized in zwitterionic electrolytes (glutamate, gamma-aminobutyric acid, glycine) instead of NaCl. Under these conditions, secretion occurs in response to provision of either GTP[S] [in the effective absence of Ca2+ (pCa 9)] or Ca2+ (in the absence of guanine nucleotide). Secretion induced by GTP[S] is strongly promoted by the presence of Mg2+ at concentrations in the millimolar range; this promotion by Mg2+ declines as the concentration of Ca2+ is elevated towards pCa 7. At pCa 6, Mg2+ is without effect. Ca(2+)-induced secretion requires the provision of MgATP. Since this is further enhanced by low concentrations (< 100 microM) and then inhibited by high concentrations of GDP, the essential role of ATP is likely to be in the maintenance of GTP via transphosphorylation by a nucleoside diphosphate kinase reaction. Thus, under conditions of high affinity (glutamate environment), GTP[S] alone is capable of inducing exocytosis. Ca2+ acts in concert with guanine nucleotides: it enhances the rate and extent of secretion and increases the affinity for Mg2+ and guanine nucleotides in the activation of the GTP-binding protein (GE

  9. A neurotensin antagonist, SR 48692, inhibits colonic responses to immobilization stress in rats.

    PubMed Central

    Castagliuolo, I; Leeman, S E; Bartolak-Suki, E; Nikulasson, S; Qiu, B; Carraway, R E; Pothoulakis, C

    1996-01-01

    We previously reported that short-term immobilization stress of rats causes increased colonic mucin release, goblet cell depletion, prostaglandin E2 secretion, and colonic mast cell activation, as well as increased colonic motility. The purpose of this study was to investigate whether neurotensin (NT), a peptide expressed in both brain and digestive tract, participates in these responses. Rats were pretreated with SR 48692 (1 mg/kg, i.p.), an NT antagonist, 15 min before immobilization (30 min). The administration of the antagonist significantly inhibited stress-mediated secretion of colonic mucin, prostaglandin E2, and a product of rat mast cells, rat mast cell protease II (P < 0.05), but did not alter the increase in fecal pellet output caused by immobilization stress. Immobilization stress also resulted in a quantifiable decrease in the abundance of NT receptor mRNA in rat colon compared with that in colonic tissues from nonimmobilized rats as measured by densitometric analysis of in situ hybridization studies (P < 0.03). We conclude that the peptide NT is involved in colonic goblet cell release and mucosal mast cell activation after immobilization stress. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:8901630

  10. Chondroitin sulphate inhibits connective tissue mast cells

    PubMed Central

    Theoharides, T C; Patra, P; Boucher, W; Letourneau, R; Kempuraj, D; Chiang, G; Jeudy, S; Hesse, Leah; Athanasiou, A

    2000-01-01

    Mast cells derive from the bone marrow and are responsible for the development of allergic and possibly inflammatory reactions. Mast cells are stimulated by immunoglobulin E (IgE) and specific antigen, but also by a number of neuropeptides such as neurotensin (NT), somatostatin or substance P (SP), to secrete numerous pro-inflammatory molecules that include histamine, cytokines and proteolytic enzymes.Chondroitin sulphate, a major constituent of connective tissues and of mast cell secretory granules, had a dose-dependent inhibitory effect on rat peritoneal mast cell release of histamine induced by the mast cell secretagogue compound 48/80 (48/80). This inhibition was stronger than that of the clinically available mast cell ‘stabilizer' disodium cromoglycate (cromolyn). Inhibition by chondroitin sulphate increased with the length of preincubation and persisted after the drug was washed off, while the effect of cromolyn was limited by rapid tachyphylaxis.Immunologic stimulation of histamine secretion from rat connective tissue mast cells (CTMC) was also inhibited, but this effect was weaker in umbilical cord-derived human mast cells and was absent in rat basophilic leukemia (RBL) cells which are considered homologous to mucosal mast cells (MMC). Oligo- and monosaccharides were not as effective as the polysaccharides.Inhibition, documented by light and electron microscopy, involved a decrease of intracellular calcium ion levels shown by confocal microscopy and image analysis. Autoradiography at the ultrastructural level showed that chondroitin sulphate was mostly associated with plasma and perigranular membranes.Chondroitin sulphate appears to be a potent mast cell inhibitor of allergic and nonimmune stimulation with potential clinical implications. PMID:11082109

  11. Inflammatory oedema induced by phospholipases A2 isolated from Crotalus durissus sp. in the rat dorsal skin: a role for mast cells and sensory C-fibers.

    PubMed

    Câmara, Paula R S; Esquisatto, Laura C M; Camargo, Enilton A; Ribela, Maria Teresa C P; Toyama, Marcos H; Marangoni, Sergio; De Nucci, Gilberto; Antunes, Edson

    2003-06-01

    The ability of the phospholipases A(2) (PLA(2)s) from Crotalus durissus cascavella, Crotalus durissus collilineatus and Crotalus durissus terrificus venoms and crotapotin to increase the vascular permeability in the rat skin as well as the contribution of both mast cells and sensory C-fibers have been investigated in this study. Vascular permeability was measured as the plasma extravascular accumulation at skin sites of intravenously injected 125I-human serum albumin. Intradermal injection of crotalic PLA(2)s (0.05-0.5 microg/site) in the rat skin resulted in dose-dependent increase in plasma extravascular whereas crotapotin (1 microg/site) failed to affect this response. Co-injection of crotapotin (1 microg/site) did not modify the increased vascular permeability induced by the PLA(2)s (0.05-0.5 microg/site). Previous treatment (30 min) of the animals with cyproheptadine (2 mg/kg, i.p.) markedly reduced PLA(2) (0.5 microg/site)-induced oedema. In rats treated neonatally with capsaicin to deplete neuropeptides, the plasma extravasation induced by all PLA(2)s (0.5 microg/site) was also significantly reduced. Similarly, the tachykinin NK(1) receptor antagonist SR140333 (1nmol/site) significantly reduced the PLA(2)-induced oedema. In addition, the combination of SR140333 with cyproheptadine further reduced the increased plasma extravasation by PLA(2) from C. d. cascavella venom, but not by PLA(2) from C. d. terrificus and C. d. collilineatus venoms. Our results suggest that increase in skin vascular permeability by crotalic PLA(2)s is mediated by activation of sensory C-fibers culminating in the release of substance P, as well as by activation of mast cells which in turn release amines such as histamine and serotonin.

  12. Haploidentical bone marrow transplantation without T-cell depletion.

    PubMed

    Chang, Ying-Jun; Huang, Xiao-Jun

    2012-12-01

    Approaches for haploidentical bone marrow transplantation (BMT) without T-cell depletion have been designed using new transplant strategies, including anti-thymocyte globulin (ATG) preparative regimens, granulocyte colony-stimulating factor-primed grafts, post-transplantation rapamycin, or high-dose cyclophosphamide (Cy) in combination with other immunosuppressive agents for graft-versus-host disease (GVHD) prophylaxis. These strategies ensured fast hematologic engraftment across the human leukocyte antigen (HLA) barrier with an acceptable incidence of GVHD. Long-term follow-up results from different transplant centers suggest that unmanipulated transplantation may provide an alternative strategy in the haploidentical setting without requiring the technical expertise and cost of ex vivo T-cell depletion. This review discusses immune reconstitution and factors associated with clinical outcomes following unmanipulated haploidentical hematopoietic stem cell transplantation (HSCT), and compares outcomes between unmanipulated haploidentical transplant versus HLA-matched sibling donor (MSD) transplantation, HLA-matched unrelated donor (MUD) transplantation, or unrelated double umbilical cord blood (dUCB) transplantation. Advantages and disadvantages of unmanipulated haploidentical HSCT and strategies to improve outcome after haploidentical BMT without ex vivo T-cell depletion are discussed. PMID:23206842

  13. Gender-Related Effects of Sex Steroids on Histamine Release and FcεRI Expression in Rat Peritoneal Mast Cells

    PubMed Central

    Muñoz-Cruz, Samira; Mendoza-Rodríguez, Yolanda; Nava-Castro, Karen E.; Yepez-Mulia, Lilián; Morales-Montor, Jorge

    2015-01-01

    Mast cells (MCs) are versatile effector and regulatory cells in various physiologic, immunologic, and pathologic processes. In addition to the well-characterized IgE/FcεRI-mediated degranulation, a variety of biological substances can induce MCs activation and release of their granule content. Sex steroids, mainly estradiol and progesterone, have been demonstrated to elicit MCs activation. Most published studies have been conducted on MCs lines or freshly isolated peritoneal and bone marrow-derived MC without addressing gender impact on MC response. Our goal was to investigate if the effect of estradiol, progesterone, testosterone, and dihydrotestosterone (DHT) on MCs may differ depending on whether female or male rats are used as MCs donors. Our results demonstrated that effect of sex steroids on MCs histamine release is dose- and gender-dependent and can be direct, synergistic, or inhibitory depending on whether hormones are used alone or to pretreat MCs followed by substance P-stimulation or upon IgE-mediated stimulation. In contrast, sex steroids did not have effect on the MC expression of the IgE high affinity receptor, FcεRI, no matter female or male rats were used. In conclusion, MCs degranulation is modulated by sex hormones in a gender-selective fashion, with MC from females being more susceptible than MC from males to the effects of sex steroids. PMID:25973435

  14. Mast cells and inflammation

    PubMed Central

    Theoharides, Theoharis C.; Alysandratos, Konstantinos-Dionysios; Angelidou, Asimenia; Delivanis, Danae-Anastasia; Sismanopoulos, Nikolaos; Zhang, Bodi; Asadi, Shahrzad; Vasiadi, Magdalini; Weng, Zuyi; Miniati, Alexandra; Kalogeromitros, Dimitrios

    2012-01-01

    Mast cells are well known for their role in allergic and anaphylactic reactions, as well as their involvement in acquired and innate immunity. Increasing evidence now implicates mast cells in inflammatory diseases where they are activated by non-allergic triggers, such as neuropeptides and cytokines, often exerting synergistic effects as in the case of IL-33. Mast cells can also release pro-inflammatory mediators selectively without degranulation. In particular, IL-1 induces selective release of IL-6, while corticotropin-releasing hormone secreted under stress induces the release of vascular endothelial growth factor. Many inflammatory diseases involve mast cells in cross-talk with T cells, such as atopic dermatitis, psoriasis and multiple sclerosis, which all worsen by stress. How mast cell differential responses are regulated is still unresolved. Preliminary evidence suggests that mitochondrial function and dynamics control mast cell degranulation, but not selective release. Recent findings also indicate that mast cells have immunomodulatory properties. Understanding selective release of mediators could explain how mast cells participate in numerous diverse biologic processes, and how they exert both immunostimulatory and immunosuppressive actions. Unraveling selective mast cell secretion could also help develop unique mast cell inhibitors with novel therapeutic applications. PMID:21185371

  15. Activation and inhibition of calcium-dependent histamine secretion by ATP ions applied to rat mast cells.

    PubMed Central

    Cockcroft, S; Gomperts, B D

    1979-01-01

    1. The concentration dependence on ATP of mast cell histamine secretion in the presence of various concentrations of Mg2+ and Ca2+ confirms that the agonist form of ATP is the free form of ATP (ATP(free) not bound to divalent cations, i.e. ATP4-. It induces 50% activation at about 1.2 microM, maximal secretion at about 2.7 microM and 50% self-inhibition at about 4.4 microM. 2. The divalent cations Mg2+ and Ca2+ were used to buffer ATP(tree) in the range 1-8 microM in the presence of much higher concentrations of ATP(total). In addition to its effect as a buffer for ATP, Ca2+ is required for secretion. 3. With ATP(free) at 1 microM, the time-course of histamine secretion is characterized by a delay of about 10 min before secretion commences. With increasing concentration of ATP(free) the delay becomes shorter (less than 5 min with ATP(free) at 2 microM). 4. Secretion commences promptly on addition of Ca2+ to cells which have been pretreated with low concentrations of ATP(free) (less than 2 microM). This observation suggests that the delay normally observed represents the time taken for Ca2+ sensitivity to develop (i.e. probably the time taken for Ca2+ channels to open). 5. Late addition of Ca2+ to cells pretreated with higher concentrations of ATP(free) (greater than 2 microM) results in a reduced amount of histamine secretion compared with that which normally occurs. This reduction (which increases with time of exposure to ATP) and the self-inhibition due to higher concentrations of ATP(free) may be two facets of a common inhibitory mechanism. 6. These results are discussed in the light of other experiments which show that mast cells treated with ATP(free) at self-inhibitory concentrations become permeable to phosphorylated metabolites and nucleotides. PMID:93638

  16. NK cell depletion diminish tumour-specific B cell responses.

    PubMed

    Jensen, Markus; Tawadros, Samir; Sedlacek, Hans-Harald; Schultze, Joachim L; Berthold, Frank

    2004-05-15

    Natural killer (NK) cells can exercise immediate cytotoxicity against malignant cells and thus far modulate the development of tumour directed T cell immunity. To investigate the impact of NK cells on the development of tumour directed B cell immunity mice were immunised with IMR5-75 human neuroblastoma cells with or without prior in vivo NK cell depletion. Flow cytometry analyses gave evidence for an impaired IgG response against the cells immunised with. Dissection of Th1 (IgG2a) and Th2 (IgG1) oriented B cell responses revealed Th1 responses as primarily affected, while Th2 oriented B cell responses as measured by flow cytometry and GD2 ganglioside-specific ELISA were enforced. The data reveal an unexpected impact of NK cells on the development of tumour directed B cell responses. Consequently, NK cell function has also to be taken into account when developing B cell-based cancer immunotherapy.

  17. Stem cell factor potentiates histamine secretion by multiple mechanisms, but does not affect tumour necrosis factor-alpha release from rat mast cells.

    PubMed Central

    Lin, T J; Bissonnette, E Y; Hirsh, A; Befus, A D

    1996-01-01

    The effect of stem cell factor (SCF) on histamine and tumour necrosis factor-alpha (TNF-alpha) release from rat peritoneal mast cells (PMC) was determined and the intracellular pathways involved in the potentiation of histamine secretion were investigated. The effects of SCF (2-100 ng/ml) were examined following both short-term (0 and 20 min) and long-term (up to 24hr) preincubations with SCF. Pretreatment of PMC with SCF for 0 min (concurrent) or 20 min did not induce histamine secretion directly, but significantly increased antigen (Ag)-induced histamine secretion. SCF potentiated Ag-induced intracellular Ca2+ increase and calcium ionophore A23187-induced histamine secretion. Pertussis toxin (PT) inhibited SCF-induced potentiation of IgE-dependent histamine secretion, indicating that PT-sensitive G-proteins are involved in the immediate effects of SCF. In long-term incubation experiments, SCF pretreatment for 18-24 hr significantly enhanced Ag-induced histamine secretion, but did not affect Ag-induced intracellular Ca2+ levels. The effects of long-term incubation with SCF, but not the short-term effects, were blocked by cycloheximide. Interestingly, spontaneous and Ag-induced TNF-alpha release from rat PMC were not affected by pretreatment with SCF (2-500 ng/ml) for 1 to 24 hr. Thus, through immediate and delayed mechanisms, SCF potentiates histamine release from PMC, but has not effect on TNF-alpha release. The regulation of MC by SCF may be important in allergic and other inflammatory diseases. PMID:8943730

  18. Pulmonary neutrophil recruitment and bronchial reactivity in formaldehyde-exposed rats are modulated by mast cells and differentially by neuropeptides and nitric oxide

    SciTech Connect

    Lino dos Santos Franco, Adriana; Damazo, Amilcar Sabino; Beraldo de Souza, Hyula Regines; Domingos, Helory Vanni; Oliveira-Filho, Ricardo Martins; Oliani, Sonia Maria; Costa, Soraia Katia Pereira; Tavares de Lima, Wothan . E-mail: wtdelima@icb.usp.br

    2006-07-01

    We have used a pharmacological approach to study the mechanisms underlying the rat lung injury and the airway reactivity changes induced by inhalation of formaldehyde (FA) (1% formalin solution, 90 min once a day, 4 days). The reactivity of isolated tracheae and intrapulmonary bronchi were assessed in dose-response curves to methacholine (MCh). Local and systemic inflammatory phenomena were evaluated in terms of leukocyte countings in bronchoalveolar lavage (BAL) fluid, blood, bone marrow lavage and spleen. Whereas the tracheal reactivity to MCh did not change, a significant bronchial hyporesponsiveness (BHR) was found after FA inhalation as compared with naive rats. Also, FA exposure significantly increased the total cell numbers in BAL, in peripheral blood and in the spleen, but did not modify the counts in bone marrow. Capsaicin hindered the increase of leukocyte number recovered in BAL fluid after FA exposure. Both compound 48/80 and indomethacin were able to prevent the lung neutrophil influx after FA, but indomethacin had no effect on that of mononuclear cells. Following FA inhalation, the treatment with sodium cromoglycate (SCG), but not with the nitric oxide (NO) synthase inhibitor L-NAME, significantly reduced the total cell number in BAL. Compound 48/80, L-NAME and SCG significantly prevented BHR to MCh after FA inhalation, whereas capsaicin was inactive in this regard. On the other hand, indomethacin exacerbated BHR. These data suggest that after FA inhalation, the resulting lung leukocyte influx and BHR may involve nitric oxide, airway sensory fibers and mast cell-derived mediators. The effect of NO seemed to be largely restricted to the bronchial tonus, whereas neuropeptides appeared to be linked to the inflammatory response, therefore indicating that the mechanisms responsible for the changes of airway responsiveness caused by FA may be separate from those underlying its inflammatory lung effects.

  19. Mast Cell Function

    PubMed Central

    da Silva, Elaine Zayas Marcelino; Jamur, Maria Célia

    2014-01-01

    Since first described by Paul Ehrlich in 1878, mast cells have been mostly viewed as effectors of allergy. It has been only in the past two decades that mast cells have gained recognition for their involvement in other physiological and pathological processes. Mast cells have a widespread distribution and are found predominantly at the interface between the host and the external environment. Mast cell maturation, phenotype and function are a direct consequence of the local microenvironment and have a marked influence on their ability to specifically recognize and respond to various stimuli through the release of an array of biologically active mediators. These features enable mast cells to act as both first responders in harmful situations as well as to respond to changes in their environment by communicating with a variety of other cells implicated in physiological and immunological responses. Therefore, the critical role of mast cells in both innate and adaptive immunity, including immune tolerance, has gained increased prominence. Conversely, mast cell dysfunction has pointed to these cells as the main offenders in several chronic allergic/inflammatory disorders, cancer and autoimmune diseases. This review summarizes the current knowledge of mast cell function in both normal and pathological conditions with regards to their regulation, phenotype and role. PMID:25062998

  20. Sporothrix schenckii yeasts induce ERK pathway activation and secretion of IL-6 and TNF-α in rat mast cells, but no degranulation.

    PubMed

    Romo-Lozano, Yolanda; Hernández-Hernández, Francisca; Salinas, Eva

    2014-11-01

    Sporothrix schenckii is a dimorphic fungus that causes sporotrichosis, a subcutaneous mycosis found throughout the world in humans and other mammals. After contact with conidia, transition to the yeast stage is required for establishment of infection. Mast cells are one of the first components of the immune system to make contact with invading pathogens. They release potent mediators that are decisive in initiating and directing the course of immune and inflammatory responses in the host. It remains unknown whether or not yeast cells of S. schenckii activate mast cells. Our aim in this study was to evaluate the in vitro response of mast cells to S. schenckii yeasts cells. Mast cells became activated after interaction with the yeasts, although exocytosis of preformed mediators was not stimulated. Sporothrix schenckii yeasts induced the release of early response cytokines such as tumor necrosis factor alpha (TNF-α) and interleukin (IL)-6 and activation of the extracellular signal-regulated kinase (ERK) signaling pathway in mast cells. As TNF-α and IL-6 are considered crucial mediators in the defense of the host against fungal disease, the release of both mediators from mast cells may contribute to the overall response of the host immune system during S. schenckii infection. PMID:25262023

  1. Sporothrix schenckii yeasts induce ERK pathway activation and secretion of IL-6 and TNF-α in rat mast cells, but no degranulation.

    PubMed

    Romo-Lozano, Yolanda; Hernández-Hernández, Francisca; Salinas, Eva

    2014-11-01

    Sporothrix schenckii is a dimorphic fungus that causes sporotrichosis, a subcutaneous mycosis found throughout the world in humans and other mammals. After contact with conidia, transition to the yeast stage is required for establishment of infection. Mast cells are one of the first components of the immune system to make contact with invading pathogens. They release potent mediators that are decisive in initiating and directing the course of immune and inflammatory responses in the host. It remains unknown whether or not yeast cells of S. schenckii activate mast cells. Our aim in this study was to evaluate the in vitro response of mast cells to S. schenckii yeasts cells. Mast cells became activated after interaction with the yeasts, although exocytosis of preformed mediators was not stimulated. Sporothrix schenckii yeasts induced the release of early response cytokines such as tumor necrosis factor alpha (TNF-α) and interleukin (IL)-6 and activation of the extracellular signal-regulated kinase (ERK) signaling pathway in mast cells. As TNF-α and IL-6 are considered crucial mediators in the defense of the host against fungal disease, the release of both mediators from mast cells may contribute to the overall response of the host immune system during S. schenckii infection.

  2. B CELL DEPLETION THERAPY EXACERBATES MURINE PRIMARY BILIARY CIRRHOSIS

    PubMed Central

    Dhirapong, Amy; Lleo, Ana; Yang, Guo-Xiang; Tsuneyama, Koichi; Dunn, Robert; Kehry, Marilyn; Packard, Thomas A.; Cambier, John C.; Liu, Fu-Tong; Lindor, Keith; Coppel, Ross L.; Ansari, Aftab A.; Gershwin, M. Eric

    2010-01-01

    Primary biliary cirrhosis (PBC) is considered a model autoimmune disease due to the clinical homogeneity of patients and the classic hallmark of anti-mitochondrial antibodies (AMAS). Indeed, the presence of AMAS is the most highly directed and specific autoantibody in autoimmune diseases. However, the contribution of B cells to the pathogenesis of PBC is unclear. Thus, although AMAs appear to interact with the biliary cell apotope and contribute to biliary pathology, there is no correlation of disease severity and titer of AMA. The recent development of well characterized mAbs specific for the B cell populations, anti-CD20 and anti-CD79, and the development of a well defined xenobiotic induced model of autoimmune cholangitis, prompted us to utilize these reagents and the model to address the contribution of B cells in the pathogenesis of murine PBC. Prior to the induction of autoimmune cholangitis, mice were treated with either anti-CD20, anti-CD79, or isotype matched control mAb and followed for B cell development, the appearance of AMAs, liver pathology and cytokine production. Results of the studies reported herein show that the in vivo depletion of B cells using either anti-CD20 or anti-CD79 led to the development of a more severe form of cholangitis than control mice which is in contrast with results from a number of other autoimmune models which have documented an important therapeutic role of B cell specific depletion. The anti-CD20/CD79 treated mice have increased liver T cell infiltrates and higher levels of pro-inflammatory cytokines. In conclusion, our results reflect a novel disease protective role of B cells in PBC and suggest that B cell depletion therapy in humans with PBC should be approached with caution. PMID:21274873

  3. Responses of dermal mast cells to injury.

    PubMed Central

    el Sayed, S O; Dyson, M

    1993-01-01

    The effect on dermal mast cell numbers and degranulation of making a partial thickness skin wound on the right flank of Wistar rats was studied immediately after operation and 0.5, 1, 2, 4, 8, 16, 24 and 72 h postoperatively. An equivalent area of intact dermis on the left flank was used as a control. In the injured dermis the mean number of detectable mast cells in the experimental group immediately after making the partial thickness wound was not significantly different from the control side (P > 0.25) but it later decreased, reaching its lowest value after 2 h and increasing from 16 h to 72 h postoperatively when the final assessment was made. The possibility that the reduction in mast cell number per unit area might be an artefact resulting from increased tissue volume due to oedema was investigated and disproved. The total number of dermal mast cells in equivalent areas of the intact left flank remained unchanged throughout this period. The percentage of degranulating mast cells started rising 0.5 h postoperatively, increased gradually to reach its highest value after 2 h, remained high up to 8 h postoperatively and then decreased to reach its lowest value after 72 h. The percentage of degranulating mast cells of the intact dermis of the left flank did not alter during this period. The lack of a significant change in the control groups shows either the absence of any systemic effect or that the technique used was not sensitive enough to detect it. Images Fig. 1 Fig. 2 Fig. 3 PMID:8226292

  4. Mast Cells and Neuroinflammation

    PubMed Central

    Dong, Hongquan; Zhang, Xiang; Qian, Yanning

    2014-01-01

    It has been determined that there is extensive communication between the immune system and the central nervous system (CNS). Proinflammatory cytokines play a key role in this communication. There is an emerging realization that glia and microglia, in particular, (which are the brain’s resident macrophages), are an important source of inflammatory mediators and may have fundamental roles in CNS disorders. Microglia respond also to proinflammatory signals released from other non-neuronal cells, principally those of immune origin, such as mast cells. Mast cells reside in the CNS and are capable of migrating across the blood-brain barrier (BBB) in situations where the barrier is compromised as a result of CNS pathology. Mast cells are both sensors and effectors in communication among nervous, vascular, and immune systems. In the brain, they reside on the brain side of the BBB, and interact with astrocytes, microglia, and blood vessels via their neuroactive stored and newly synthesized chemicals. They are first responders, acting as catalysts and recruiters to initiate, amplify, and prolong other immune and nervous responses upon activation. Mast cells both promote deleterious outcomes in brain function and contribute to normative behavioral functioning, particularly cognition and emotion. Mast cells may play a key role in treating systemic inflammation or blockade of signaling pathways from the periphery to the brain. PMID:25529562

  5. Mast cells and mastocytosis

    PubMed Central

    2008-01-01

    Mast cells have been recognized for well over 100 years. With time, human mast cells have been documented to originate from CD34+ cells, and have been implicated in host responses in both innate and acquired immunity. In clinical immunology, they are recognized for their central role in IgE-mediated degranulation and allergic inflammation by virtue of their expression of the high-affinity receptor for IgE and release of potent proinflammatory mediators. In hematology, the clinical disease of mastocytosis is characterized by a pathologic increase of mast cells in tissues, often associated with mutations in KIT, the receptor for stem cell factor. More recently, and with increased understanding of how human mast cells are activated through receptors including the high-affinity receptor for IgE and KIT, specific tyrosine kinase inhibitors have been identified with the potential to interrupt signaling pathways and thus limit the proliferation of mast cells as well as their activation through immunoglobulin receptors. PMID:18684881

  6. Mast cells and company.

    PubMed

    Jönsson, Friederike; Daëron, Marc

    2012-01-01

    Classically, allergy depends on IgE antibodies and on high-affinity IgE receptors expressed by mast cells and basophils. This long accepted IgE/FcεRI/mast cell paradigm, on which the definition of immediate hypersensitivity was based in the Gell and Coomb's classification, appears too reductionist. Recently accumulated evidence indeed requires that not only IgE but also IgG antibodies, that not only FcεRI but also FcγR of the different types, that not only mast cells and basophils but also neutrophils, monocytes, macrophages, eosinophils, and other myeloid cells be considered as important players in allergy. This view markedly changes our understanding of allergic diseases and, possibly, their treatment.

  7. Mast Cell and Autoimmune Diseases

    PubMed Central

    Xu, Yunzhi; Chen, Guangjie

    2015-01-01

    Mast cells are important in innate immune system. They have been appreciated as potent contributors to allergic reaction. However, increasing evidence implicates the important role of mast cells in autoimmune disease like rheumatoid arthritis and multiple sclerosis. Here we review the current stage of knowledge about mast cells in autoimmune diseases. PMID:25944979

  8. Mast cell and autoimmune diseases.

    PubMed

    Xu, Yunzhi; Chen, Guangjie

    2015-01-01

    Mast cells are important in innate immune system. They have been appreciated as potent contributors to allergic reaction. However, increasing evidence implicates the important role of mast cells in autoimmune disease like rheumatoid arthritis and multiple sclerosis. Here we review the current stage of knowledge about mast cells in autoimmune diseases. PMID:25944979

  9. CD4+ T Cells Drive Goblet Cell Depletion during Citrobacter rodentium Infection

    PubMed Central

    Chan, Justin M.; Bhinder, Ganive; Sham, Ho Pan; Ryz, Natasha; Huang, Tina; Bergstrom, Kirk S.

    2013-01-01

    Both idiopathic and infectious forms of colitis disrupt normal intestinal epithelial cell (IEC) proliferation and differentiation, although the mechanisms involved remain unclear. Recently, we demonstrated that infection by the attaching and effacing murine pathogen Citrobacter rodentium leads to a significant reduction in colonic goblet cell numbers (goblet cell depletion). This pathology depends on T and/or B cells, as Rag1−/− mice do not suffer this depletion during infection, instead suffering high mortality rates. To address the immune mechanisms involved, we reconstituted Rag−/− mice with either CD4+ or CD8+ T cells. Both T cell subsets increased Rag1−/− mouse survival during infection, with mice that received CD8+ T cells developing colonic ulcers but not goblet cell depletion. In contrast, mice that received CD4+ T cells showed goblet cell depletion in concert with exaggerated IEC proliferation. To define the possible involvement of T cell-derived cytokines, we infected gamma interferon receptor gene knockout (IFN-γR−/−) mice and wild-type mice given interleukin 17A (IL-17A) neutralizing antibodies and found that IFN-γ signaling was required for both goblet cell depletion and increased IEC proliferation. Immunostaining revealed that C. rodentium cells preferentially localized to nonhyperplastic crypts containing numerous goblet cells, whereas hyperplastic, goblet cell-depleted crypts appeared protected from infection. To address whether goblet cell depletion benefits the C. rodentium-infected host, we increased goblet cell numbers using the γ-secretase inhibitor dibenzazepine (DBZ), which resulted in greatly increased pathogen burdens and mortality rates. These results demonstrate that goblet cell depletion reflects host immunomodulation of IEC homeostasis and reflects a novel host defense mechanism against mucosal-adherent pathogens. PMID:24101690

  10. 5-Hydroxytryptamine receptor agonists for the abortive treatment of vascular headaches block mast cell, endothelial and platelet activation within the rat dura mater after trigeminal stimulation.

    PubMed

    Buzzi, M G; Dimitriadou, V; Theoharides, T C; Moskowitz, M A

    1992-06-26

    Antidromic stimulation of small caliber trigeminal axons causes neurogenic inflammation in the dura mater and tongue as evidenced by marked increases in mast cell activation, protein extravasation, as well as in the numbers of endothelial cytoplasmic vesicles, endothelial microvilli and platelet aggregates within ipsilateral post-capillary venules. In this report, we examined the effects of pretreatment with serotonin1 receptor agonists, dihydroergotamine (50 micrograms/kg, i.v.) and sumatriptan (100 micrograms/kg, i.v.) on the light and electron microscopic changes which develop after trigeminal ganglion stimulation. Both dihydroergotamine and sumatriptan are useful in the acute treatment of vascular headaches and bind with high affinity to 5-HT1D receptors. Both drugs decreased significantly the number of dural vessels showing endothelial or platelet changes and the numbers of activated mast cells, but did not affect the neurogenic response in the tongue. The drugs also blocked the accumulation of horseradish peroxidase reaction product within the endothelium and perivascular space on the stimulated side. The receptor is not present on trigeminovascular fibers innervating extracranial cephalic tissues. Drug mechanism probably involves inhibition of a proximal step in the pathophysiological cascade (e.g., via activation of a prejunctional receptor) because (a) receptors for sumatriptan have not been identified on mast cells whereas the inflammatory response was attenuated in mast cells as well as within platelets and the endothelium and (b) previous work indicates that sumatriptan and dihydroergotamine block neurotransmitter release. Hence, constriction of vascular smooth muscle mediated by postjunctional 5-hydroxytryptamine receptors is unlikely to explain the anti-inflammatory actions of dihydroergotamine or sumatriptan reported here.

  11. Local stem cell depletion model for radiation myelitis

    SciTech Connect

    Yaes, R.J.; Kalend, A.

    1988-06-01

    We propose a model for normal tissue damage based on the assumption that adult mammalian stem cells have limited mobility and, consequently, for each organ, there is a maximum volume (the critical volume, Vc), that can be repopulated and repaired by a single surviving stem cell. This concept is applied to a simple, 1-dimensional model of the spinal cord, where the critical volume is a slice of thickness, t, assumed to be small compared to lengths of spinal cord usually irradiated clinically. The probability of myelitis is explicitly obtained as a function of the dose, dose per fraction, length of cord irradiated, slice thickness, number of stem cells per slice and parameters alpha and beta of the stem cell survival curve. The complication probability is expressed as a triple negative exponential function of dose analogous to the double negative exponential function for tumor control, resulting in a steep dose-response curve with short tails in both the high dose and low dose regions. We show that the model predictions are compatible with the experimental data for radiation myelitis in the rat. We discuss how this concept can be applied to other organs such as skin and to organs composed of structurally and functionally distinct subunits, such as the kidney.

  12. Generation of leukotrienes by purified human lung mast cells.

    PubMed Central

    MacGlashan, D W; Schleimer, R P; Peters, S P; Schulman, E S; Adams, G K; Newball, H H; Lichtenstein, L M

    1982-01-01

    Although mediator release from mast cells and basophils plays a central role in the pathogenesis of human allergic disease, biochemical studies have been restricted to rat peritoneal mast cells and basophilic leukemia cells because they could be easily purified. We have used two new techniques of cell separation to purify human lung mast cells to 98% homogeneity. Lung cell suspensions were obtained by dispersion of chopped lung tissue with proteolytic enzymes. Mast cells were then purified from the suspensions by countercurrent centrifugal elutriation and affinity chromatography. The purified mast cells released both histamine and slow-reacting substance of anaphylaxis (SRS-A) (leukotriene C and D) during stimulation with goat anti-human IgE antibody. Moreover, these preparations were able to generate significant quantities of SRS-A (32 +/- 7 x 10(-17) LTD mole-equivalents/mast cell) at all stages of purification, indicating that a secondary cell is not necessary for the antigen-induced release of SRS. Images PMID:7119113

  13. Enhanced mucosal permeability and nitric oxide synthase activity in jejunum of mast cell deficient mice

    PubMed Central

    Komatsu, S; Grisham, M; Russell, J; Granger, D

    1997-01-01

    Background—Recent reports have described a modulating influence of nitric oxide (NO) on intestinal mucosal permeability and have implicated a role for mast cells in this NO mediated process. 
Aims—To assess further the contribution of mast cells to the mucosal permeability changes elicited by the NO synthase (NOS) inhibitor NG-nitro-L-arginine methylester (L-NAME), using mast cell deficient (W/WV) and mast cell replete mice (+/+). 
Methods—Chromium-51 EDTA clearance (from blood to jejunal lumen), jejunal NOS and myeloperoxidase (MPO) activities, and plasma nitrate/nitrite levels were monitored. 
Results—The increased EDTA clearance elicited by intraluminal L-NAME in W/WV mice (4.4-fold) was significantly greater than the response observed in control (+/+) mice (1.8-fold). The exacerbated response in W/Wv mice was greatly attenuated by pretreatment with either dexamethasone (1.3-fold) or the selective inducible NOS inhibitor, aminoguanidine (1.4-fold), and partially attenuated by the mast cell stabiliser, lodoxamide (2.9-fold). Jejunal inducible NOS activity was significantly higher in W/WV than in +/+ mice, while jejunal MPO was lower in W/WV mice than in +/+ mice, suggesting that the higher inducible NOS in W/WV does not result from the recruitment of inflammatory cells into the gut. The higher inducible NOS activity in the jejunum of W/WV was significantly reduced by dexamethasone treatment. 
Conclusions—Our results suggest that mast cells normally serve to inhibit inducible NOS activity tonically in the gut and that inhibitors of NOS elicit a larger permeability response when this tonic inhibitory influence is released by mast cell depletion. 

 Keywords: aminoguanidine; c-kit; dexamethasone; epithelium; neutrophils PMID:9414970

  14. Influence of ethanolic extract of Tephrosia purpurea Linn. on mast cells and erythrocytes membrane integrity.

    PubMed

    Gokhale, A B; Dikshit, V J; Damre, A S; Kulkarni, K R; Saraf, M N

    2000-08-01

    The ethanolic extract of T. purpurea Linn. was studied for its in vitro effect on rat mast cell degranulation and erythrocyte membrane integrity in vitro. The extract in concentration of 25-200 microg/ml showed a dose-dependant inhibition of rat mast cell degranulation induded by compound 48/80 and egg albumin. T. purpurea extract was found to inhibit haemolysis of erythrocytes induced by hypotonic solution but accelerated haemolysis induced by heat at a concentration of 100 microg/ml. The studies reveal that the ethanolic extract of T. purpurea may inhibit degranulation of mast cells by a mechanism other than membrane stabilization.

  15. Overview of MAST results

    NASA Astrophysics Data System (ADS)

    Chapman, I. T.; Adamek, J.; Akers, R. J.; Allan, S.; Appel, L.; Asunta, O.; Barnes, M.; Ben Ayed, N.; Bigelow, T.; Boeglin, W.; Bradley, J.; Brünner, J.; Cahyna, P.; Carr, M.; Caughman, J.; Cecconello, M.; Challis, C.; Chapman, S.; Chorley, J.; Colyer, G.; Conway, N.; Cooper, W. A.; Cox, M.; Crocker, N.; Crowley, B.; Cunningham, G.; Danilov, A.; Darrow, D.; Dendy, R.; Diallo, A.; Dickinson, D.; Diem, S.; Dorland, W.; Dudson, B.; Dunai, D.; Easy, L.; Elmore, S.; Field, A.; Fishpool, G.; Fox, M.; Fredrickson, E.; Freethy, S.; Garzotti, L.; Ghim, Y. C.; Gibson, K.; Graves, J.; Gurl, C.; Guttenfelder, W.; Ham, C.; Harrison, J.; Harting, D.; Havlickova, E.; Hawke, J.; Hawkes, N.; Hender, T.; Henderson, S.; Highcock, E.; Hillesheim, J.; Hnat, B.; Holgate, J.; Horacek, J.; Howard, J.; Huang, B.; Imada, K.; Jones, O.; Kaye, S.; Keeling, D.; Kirk, A.; Klimek, I.; Kocan, M.; Leggate, H.; Lilley, M.; Lipschultz, B.; Lisgo, S.; Liu, Y. Q.; Lloyd, B.; Lomanowski, B.; Lupelli, I.; Maddison, G.; Mailloux, J.; Martin, R.; McArdle, G.; McClements, K.; McMillan, B.; Meakins, A.; Meyer, H.; Michael, C.; Militello, F.; Milnes, J.; Morris, A. W.; Motojima, G.; Muir, D.; Nardon, E.; Naulin, V.; Naylor, G.; Nielsen, A.; O'Brien, M.; O'Gorman, T.; Ono, Y.; Oliver, H.; Pamela, S.; Pangione, L.; Parra, F.; Patel, A.; Peebles, W.; Peng, M.; Perez, R.; Pinches, S.; Piron, L.; Podesta, M.; Price, M.; Reinke, M.; Ren, Y.; Roach, C.; Robinson, J.; Romanelli, M.; Rozhansky, V.; Saarelma, S.; Sangaroon, S.; Saveliev, A.; Scannell, R.; Schekochihin, A.; Sharapov, S.; Sharples, R.; Shevchenko, V.; Silburn, S.; Simpson, J.; Storrs, J.; Takase, Y.; Tanabe, H.; Tanaka, H.; Taylor, D.; Taylor, G.; Thomas, D.; Thomas-Davies, N.; Thornton, A.; Turnyanskiy, M.; Valovic, M.; Vann, R.; Walkden, N.; Wilson, H.; Wyk, L. V.; Yamada, T.; Zoletnik, S.; MAST; MAST Upgrade Teams

    2015-10-01

    The Mega Ampère Spherical Tokamak (MAST) programme is strongly focused on addressing key physics issues in preparation for operation of ITER as well as providing solutions for DEMO design choices. In this regard, MAST has provided key results in understanding and optimizing H-mode confinement, operating with smaller edge localized modes (ELMs), predicting and handling plasma exhaust and tailoring auxiliary current drive. In all cases, the high-resolution diagnostic capability on MAST is complemented by sophisticated numerical modelling to facilitate a deeper understanding. Mitigation of ELMs with resonant magnetic perturbations (RMPs) with toroidal mode number nRMP = 2, 3, 4, 6 has been demonstrated: at high and low collisionality; for the first ELM following the transition to high confinement operation; during the current ramp-up; and with rotating nRMP = 3 RMPs. nRMP = 4, 6 fields cause less rotation braking whilst the power to access H-mode is less with nRMP = 4 than nRMP = 3, 6. Refuelling with gas or pellets gives plasmas with mitigated ELMs and reduced peak heat flux at the same time as achieving good confinement. A synergy exists between pellet fuelling and RMPs, since mitigated ELMs remove fewer particles. Inter-ELM instabilities observed with Doppler backscattering are consistent with gyrokinetic simulations of micro-tearing modes in the pedestal. Meanwhile, ELM precursors have been strikingly observed with beam emission spectroscopy (BES) measurements. A scan in beta at the L-H transition shows that pedestal height scales strongly with core pressure. Gyro-Bohm normalized turbulent ion heat flux (as estimated from the BES data) is observed to decrease with increasing tilt of the turbulent eddies. Fast ion redistribution by energetic particle modes depends on density, and access to a quiescent domain with ‘classical’ fast ion transport is found above a critical density. Highly efficient electron Bernstein wave current drive (1 A W-1) has been achieved

  16. Overview of MAST results

    NASA Astrophysics Data System (ADS)

    Counsell, G. F.; Akers, R. J.; Appel, L. C.; Applegate, D.; Axon, K. B.; Baranov, Y.; Brickley, C.; Bunting, C.; Buttery, R. J.; Carolan, P. G.; Challis, C.; Ciric, D.; Conway, N. J.; Cox, M.; Cunningham, G.; Darke, A.; Dnestrovskij, A.; Dowling, J.; Dudson, B.; Dunstan, M. R.; Delchambre, E.; Field, A. R.; Foster, A.; Gee, S.; Gryaznevich, M. P.; Helander, P.; Hender, T. C.; Hole, M.; Howell, D. H.; Joiner, N.; Keeling, D.; Kirk, A.; Lehane, I. P.; Lisgo, S.; Lloyd, B.; Lott, F.; Maddison, G. P.; Manhood, S. J.; Martin, R.; McArdle, G. J.; McClements, K. G.; Meyer, H.; Morris, A. W.; Nelson, M.; O'Brien, M. R.; Patel, A.; Pinfold, T.; Preinhaelter, J.; Price, M. N.; Roach, C. M.; Rozhansky, V.; Saarelma, S.; Saveliev, A.; Scannell, R.; Sharapov, S.; Shevchenko, V.; Shibaev, S.; Stammers, K.; Storrs, J.; Sykes, A.; Tabasso, A.; Tallents, S.; Taylor, D.; Tournianski, M. R.; Turner, A.; Turri, G.; Valovic, M.; Volpe, F.; Voss, G.; Walsh, M. J.; Watkins, J. R.; Wilson, H. R.; Wisse, M.; MAST, the; NBI; ECRH Teams

    2005-10-01

    Significant progress has been made on the Mega Ampere Spherical Tokamak (MAST) towards a fundamental understanding of transport, stability and edge physics and addressing technological issues for future large devices. Collaborative studies of the L-H transition with NSTX and ASDEX Upgrade confirm that operation in a connected double-null configuration significantly reduces the threshold power, Pthr. The MAST data provide support for a theory for the transition based on finite β drift wave turbulence suppression by self-generated zonal flows. Analysis of low and high field side density gradients in the H-mode pedestal provides support for an analytical model of the density pedestal width dependent on the neutral penetration depth. Adding MAST data to international confinement databases has enhanced confidence in scalings for ITER by significantly expanding the range of β and ɛ explored and indicates a slightly stronger ɛ dependence than in current scalings. Studies of core transport have been conducted for well-diagnosed L-mode, H-mode and internal transport barrier (ITB) discharges using TRANSP, and microstability and turbulence studies have been carried out using GS2. Linear micro-stability analysis indicates that ITG modes are typically unstable on all flux surfaces with growth rates that are comparable to the equilibrium E × B flow shearing rate. Mixing length estimates of transport coefficients from ITG (neglecting flow shear) give diffusion coefficients that are broadly comparable with observed thermal diffusivities. Non-linear, collisionless ETG calculations have been performed and suggest radially extended electrostatic streamers up to 100ρe across in radius. Transport from ITG could easily be suppressed in regions where the E × B shear flow rate, ωSE, exceeds the ITG growth rate, possibly contributing to ITBs. Toroidal rotation, driven by neutral beam torque, is the dominant contribution to ωSE via the vphiBθ term in the radial electric field

  17. Effects of T-Cell Depletion on Allogeneic Hematopoietic Stem Cell Transplantation Outcomes in AML Patients

    PubMed Central

    Hobbs, Gabriela Soriano; Perales, Miguel-Angel

    2015-01-01

    Graft versus host disease (GVHD) remains one of the leading causes of morbidity and mortality associated with conventional allogeneic hematopoietic stem cell transplantation (HCT). The use of T-cell depletion significantly reduces this complication. Recent prospective and retrospective data suggest that, in patients with AML in first complete remission, CD34+ selected grafts afford overall and relapse-free survival comparable to those observed in recipients of conventional grafts, while significantly decreasing GVHD. In addition, CD34+ selected grafts allow older patients, and those with medical comorbidities or with only HLA-mismatched donors to successfully undergo transplantation. Prospective data are needed to further define which groups of patients with AML are most likely to benefit from CD34+ selected grafts. Here we review the history of T-cell depletion in AML, and techniques used. We then summarize the contemporary literature using CD34+ selection in recipients of matched or partially mismatched donors (7/8 or 8/8 HLA-matched), and provide a summary of the risks and benefits of using T-cell depletion. PMID:26239251

  18. Borrelia burgdorferi Spirochetes Induce Mast Cell Activation and Cytokine Release

    PubMed Central

    Talkington, Jeffrey; Nickell, Steven P.

    1999-01-01

    The Lyme disease spirochete, Borrelia burgdorferi, is introduced into human hosts via tick bites. Among the cell types present in the skin which may initially contact spirochetes are mast cells. Since spirochetes are known to activate a variety of cell types in vitro, we tested whether B. burgdorferi spirochetes could activate mast cells. We report here that freshly isolated rat peritoneal mast cells or mouse MC/9 mast cells cultured in vitro with live or freeze-thawed B. burgdorferi spirochetes undergo low but detectable degranulation, as measured by [5-3H] hydroxytryptamine release, and they synthesize and secrete the proinflammatory cytokine tumor necrosis factor alpha (TNF-α). In contrast to findings in previous studies, where B. burgdorferi-associated activity was shown to be dependent upon protein lipidation, mast cell TNF-α release was not induced by either lipidated or unlipidated recombinant OspA. This activity was additionally shown to be protease sensitive and surface expressed. Finally, comparisons of TNF-α-inducing activity in known low-, intermediate-, and high-passage B. burgdorferi B31 isolates demonstrated passage-dependent loss of activity, indicating that the activity is probably plasmid encoded. These findings document the presence in low-passage B. burgdorferi spirochetes of a novel lipidation-independent activity capable of inducing cytokine release from host cells. PMID:10024550

  19. Mast cell sarcoma: clinical management.

    PubMed

    Weiler, Catherine R; Butterfield, Joseph

    2014-05-01

    Mast cell sarcoma is a disorder that results in abnormal mast cells as identified by morphology, special stains, and in some publications, c-kit mutation analysis. It affects animal species such as canines more commonly than humans. In humans it is a very rare condition, with variable clinical presentation. There is no standard therapy for the disorder. It can affect any age group. It is occasionally associated with systemic mastocytosis and/or urticaria pigmentosa. The prognosis of mast cell sarcoma in published literature is very poor in humans.

  20. A mast-seeding desert shrub regulates population dynamics and behavior of its heteromyid dispersers.

    PubMed

    Auger, Janene; Meyer, Susan E; Jenkins, Stephen H

    2016-04-01

    Granivorous rodent populations in deserts are primarily regulated through precipitation-driven resource pulses rather than pulses associated with mast-seeding, a pattern more common in mesic habitats. We studied heteromyid responses to mast-seeding in the desert shrub blackbrush (Coleogyne ramosissima), a regionally dominant species in the Mojave-Great Basin Desert transition zone. In a 5-year study at Arches National Park, Utah, USA, we quantified spatiotemporal variation in seed resources in mast and intermast years in blackbrush-dominated and mixed desert vegetation and measured responses of Dipodomys ordii (Ord's kangaroo rat) and Perognathus flavescens (plains pocket mouse). In blackbrush-dominated vegetation, blackbrush seeds comprised >79% of seed production in a mast year, but 0% in the first postmast year. Kangaroo rat abundance in blackbrush-dominated vegetation was highest in the mast year, declined sharply at the end of the first postmast summer, and then remained at low levels for 3 years. Pocket mouse abundance was not as strongly associated with blackbrush seed production. In mixed desert vegetation, kangaroo rat abundance was higher and more uniform through time. Kangaroo rats excluded the smaller pocket mice from resource-rich patches including a pipeline disturbance and also moved their home range centers closer to this disturbance in a year of low blackbrush seed production. Home range size for kangaroo rats was unrelated to seed resource density in the mast year, but resource-poor home ranges were larger (P < 0.001) in the first postmast year, when resources were limiting. Blackbrush seeds are higher in protein and fat but lower in carbohydrates than the more highly preferred seeds of Indian ricegrass (Achnatherum hymenoides) and have similar energy value per unit of handling time. Kangaroo rats cached seeds of these two species in similar spatial configurations, implying that they were equally valued as stored food resources. Blackbrush mast

  1. A mast-seeding desert shrub regulates population dynamics and behavior of its heteromyid dispersers.

    PubMed

    Auger, Janene; Meyer, Susan E; Jenkins, Stephen H

    2016-04-01

    Granivorous rodent populations in deserts are primarily regulated through precipitation-driven resource pulses rather than pulses associated with mast-seeding, a pattern more common in mesic habitats. We studied heteromyid responses to mast-seeding in the desert shrub blackbrush (Coleogyne ramosissima), a regionally dominant species in the Mojave-Great Basin Desert transition zone. In a 5-year study at Arches National Park, Utah, USA, we quantified spatiotemporal variation in seed resources in mast and intermast years in blackbrush-dominated and mixed desert vegetation and measured responses of Dipodomys ordii (Ord's kangaroo rat) and Perognathus flavescens (plains pocket mouse). In blackbrush-dominated vegetation, blackbrush seeds comprised >79% of seed production in a mast year, but 0% in the first postmast year. Kangaroo rat abundance in blackbrush-dominated vegetation was highest in the mast year, declined sharply at the end of the first postmast summer, and then remained at low levels for 3 years. Pocket mouse abundance was not as strongly associated with blackbrush seed production. In mixed desert vegetation, kangaroo rat abundance was higher and more uniform through time. Kangaroo rats excluded the smaller pocket mice from resource-rich patches including a pipeline disturbance and also moved their home range centers closer to this disturbance in a year of low blackbrush seed production. Home range size for kangaroo rats was unrelated to seed resource density in the mast year, but resource-poor home ranges were larger (P < 0.001) in the first postmast year, when resources were limiting. Blackbrush seeds are higher in protein and fat but lower in carbohydrates than the more highly preferred seeds of Indian ricegrass (Achnatherum hymenoides) and have similar energy value per unit of handling time. Kangaroo rats cached seeds of these two species in similar spatial configurations, implying that they were equally valued as stored food resources. Blackbrush mast

  2. Antibacterial agent triclosan suppresses RBL-2H3 mast cell function

    SciTech Connect

    Palmer, Rachel K.; Hutchinson, Lee M.; Burpee, Benjamin T.; Tupper, Emily J.; Pelletier, Jonathan H.; Kormendy, Zsolt; Hopke, Alex R.; Malay, Ethan T.; Evans, Brieana L.; Velez, Alejandro; Gosse, Julie A.

    2012-01-01

    Triclosan is a broad-spectrum antibacterial agent, which has been shown previously to alleviate human allergic skin disease. The purpose of this study was to investigate the hypothesis that the mechanism of this action of triclosan is, in part, due to effects on mast cell function. Mast cells play important roles in allergy, asthma, parasite defense, and carcinogenesis. In response to various stimuli, mast cells degranulate, releasing allergic mediators such as histamine. In order to investigate the potential anti-inflammatory effect of triclosan on mast cells, we monitored the level of degranulation in a mast cell model, rat basophilic leukemia cells, clone 2H3. Having functional homology to human mast cells, as well as a very well defined signaling pathway leading to degranulation, this cell line has been widely used to gain insight into mast-cell driven allergic disorders in humans. Using a fluorescent microplate assay, we determined that triclosan strongly dampened the release of granules from activated rat mast cells starting at 2 μM treatment, with dose-responsive suppression through 30 μM. These concentrations were found to be non-cytotoxic. The inhibition was found to persist when early signaling events (such as IgE receptor aggregation and tyrosine phosphorylation) were bypassed by using calcium ionophore stimulation, indicating that the target for triclosan in this pathway is likely downstream of the calcium signaling event. Triclosan also strongly suppressed F-actin remodeling and cell membrane ruffling, a physiological process that accompanies degranulation. Our finding that triclosan inhibits mast cell function may explain the clinical data mentioned above and supports the use of triclosan or a mechanistically similar compound as a topical treatment for allergic skin disease, such as eczema. -- Highlights: ►The effects of triclosan on mast cell function using a murine mast cell model. ►Triclosan strongly inhibits degranulation of mast cells.

  3. B-Cell Depletion Salvage Therapy in Rapidly Progressive Dermatomyositis Related Interstitial Lung Disease.

    PubMed

    Eissa, Khaled; Palomino, Jaime

    2016-01-01

    Interstitial lung disease (ILD) is a major cause of morbidity and mortality in patients with idiopathic inflammatory myopathies (IIM). Glucocorticoids are the initial standard treatment. However, many patients fail to respond and continue to progress despite treatment with high dose glucocorticoids. The efficacy of rituximab has been suggested in case reports and case series of refractory antisynthetase (AS) syndrome, but data on patients without auto-antibodies or with rapidly progressive ILD are scarce. We report a case of rapidly progressive dermatomyositis (DM) associated ILD treated successfully with B-cell depletion therapy. PMID:27389378

  4. Effect of LED phototherapy (λ630 +/- 20nm) on mast cells during wound healing in hypothyroid

    NASA Astrophysics Data System (ADS)

    Paraguassú, Gardênia M.; De Castro, Isabele Cardoso V.; Vasconcelos, Rebeca M.; da Guarda, Milena G.; Rodriguez, Tânia T.; Ramalho, Maria José P.; Pinheiro, Antônio Luiz B.; Ramalho, Luciana Maria P.

    2014-02-01

    Hypothyroidism has been associated with the disruption of the body's metabolism, including the healing process. LED phototherapy has been studied using several healing models, but their effects on mast cells proliferation associated to hypothyroidism remains unknown. The aim of this study was to assess the effect LED (λ630+/-20nm) phototherapy on mast cells proliferation during tissue repair in hypothyroid rats. Under general anesthesia, a standard surgical wound (1cm2) was created on the dorsum of 24 male Wistar rats divided into 4 groups of 6 animals each: EC-Control Euthyroid; ED-Euthyroid+LED; HC-Control Hypothyroid and HD-Hypothyroid+LED. The irradiation started immediately after surgery and was repeated every other day for 7 days, when animals death occurred. Hypothyroidism was induced in rats with propylthiouracil (0.05g/100mL) administered orally for 4 weeks and maintained until the end of the experiment. The specimens removed were processed to wax and stained with toluidine blue for mast cell identification. The mast cell proliferation was significantly higher in HC group than in EC group (Mann Whitney, p<0.05), but when ED group was compared to HD group, no significant difference was found. Our results showed that there was increase of mast cells in the presence of hypothyroidism, prolonging the inflammatory phase of repair, and the LED light has a biomodulative effect on mast cell population, even when hipothyroidism was present.

  5. The Antiallergic Mast Cell Stabilizers Lodoxamide and Bufrolin as the First High and Equipotent Agonists of Human and Rat GPR35

    PubMed Central

    MacKenzie, Amanda E.; Caltabiano, Gianluigi; Kent, Toby C.; Jenkins, Laura; McCallum, Jennifer E.; Hudson, Brian D.; Nicklin, Stuart A.; Fawcett, Lindsay; Markwick, Rachel; Charlton, Steven J.

    2014-01-01

    Lack of high potency agonists has restricted analysis of the G protein–coupled receptor GPR35. Moreover, marked variation in potency and/or affinity of current ligands between human and rodent orthologs of GPR35 has limited their productive use in rodent models of physiology. Based on the reported modest potency of the antiasthma and antiallergic ligands cromolyn disodium and nedocromil sodium, we identified the related compounds lodoxamide and bufrolin as high potency agonists of human GPR35. Unlike previously identified high potency agonists that are highly selective for human GPR35, both lodoxamide and bufrolin displayed equivalent potency at rat GPR35. Further synthetic antiallergic ligands, either sharing features of the standard surrogate agonist zaprinast, or with lodoxamide and bufrolin, were also shown to display agonism at either human or rat GPR35. Because both lodoxamide and bufrolin are symmetric di-acids, their potential mode of binding was explored via mutagenesis based on swapping between the rat and human ortholog nonconserved arginine residues within proximity of a key conserved arginine at position 3.36. Computational modeling and ligand docking predicted the contributions of different arginine residues, other than at 3.36, in human GPR35 for these two ligands and were consistent with selective loss of potency of either bufrolin or lodoxamide at distinct arginine mutants. The computational models also suggested that bufrolin and lodoxamide would display reduced potency at a low-frequency human GPR35 single nucleotide polymorphism. This prediction was confirmed experimentally. PMID:24113750

  6. Dual effect of spermine on mast cell secretion exhibits different calcium and temperature requirements.

    PubMed

    Vliagoftis, H; Mak, L; Boucher, W; Theoharides, T C

    1999-09-01

    Mast cells release many biologically active molecules upon stimulation by a variety of molecules such as immunoglobulin E (IgE) and specific antigen, anaphylatoxins, as well as a number of cationic compounds which include drugs, kinins and neuropeptides. The effect of the naturally occurring polyamine spermine was studied because, even though it is polycationic, it has been implicated in the modulation of secretory processes in a variety of cells. In particular, it was previously shown that oxidation products of spermine inhibit mast cell secretion. High concentrations of spermine (5 x 10(-3) M) added at 37 degrees C induced mast cell secretion that had similar characteristics with that triggered by compound 48/80 (48/80). However, spermine inhibited mast cell secretion in a dose-dependent manner as long as it was added at 4-10 degrees C for at least 10 min in the absence of Ca++ before warming the cells to 37 degrees C and triggering them with 48/80. These findings were true both for purified rat peritoneal mast cells and for rat skin mast cells in situ. Addition of calcium after the cells had been warmed to 37 degrees C could not reverse this inhibition. The inhibition seen when spermine was added at 4 degrees C was, however, overcome if phorbol myristate acetate (PMA) or NaF, which activate PKC and G proteins respectively, were added to mast cells at 37 degrees C together with Ca++. These results indicate that polyamines could be important modulators of the activation state of mast cells and might help further define the biochemical events involved in mast cell secretion.

  7. Signal transduction pathways in mast cell granule-mediated endothelial cell activation.

    PubMed Central

    Chi, Luqi; Stehno-Bittel, Lisa; Smirnova, Irina; Stechschulte, Daniel J; Dileepan, Kottarappat N

    2003-01-01

    BACKGROUND: We have previously shown that incubation of human endothelial cells with mast cell granules results in potentiation of lipopolysaccharide-induced production of interleukin-6 and interleukin-8. AIMS: The objective of the present study was to identify candidate molecules and signal transduction pathways involved in the synergy between mast cell granules and lipopolysaccharide on endothelial cell activation. METHODS: Human umbilical vein endothelial cells were incubated with rat mast cell granules in the presence and absence of lipopolysaccharide, and IL-6 production was quantified. The status of c-Jun amino-terminal kinase and extracellular signal-regulated kinase 1/2 activation, nuclear factor-kappaB translocation and intracellular calcium levels were determined to identify the mechanism of synergy between mast cell granules and lipopolysaccaride. RESULTS: Mast cell granules induced low levels of interleukin-6 production by endothelial cells, and this effect was markedly enhanced by lipopolysaccharide. The results revealed that both serine proteases and histamine present in mast cell granules were involved in this activation process. Mast cell granules increased intracellular calcium, and activated c-Jun amino-terminal kinase and extracellular signal-regulated kinase 1/2. The combination of lipopolysaccharide and mast cell granules prolonged c-Jun amino-terminal kinase activity beyond the duration of induction by either stimulant alone and was entirely due to active proteases. However, both proteases and histamine contributed to calcium mobilization and extracellular signal-regulated kinase 1/2 activation. The nuclear translocation of nuclear factor-kappaB proteins was of greater magnitude in endothelial cells treated with the combination of mast cell granules and lipopolysaccharide. CONCLUSIONS:Mast cell granule serine proteases and histamine can amplify lipopolysaccharide-induced endothelial cell activation, which involves calcium mobilization, mitogen

  8. Cytoskeleton in Mast Cell Signaling

    PubMed Central

    Dráber, Pavel; Sulimenko, Vadym; Dráberová, Eduarda

    2012-01-01

    Mast cell activation mediated by the high affinity receptor for IgE (FcεRI) is a key event in allergic response and inflammation. Other receptors on mast cells, as c-Kit for stem cell factor and G protein-coupled receptors (GPCRs) synergistically enhance the FcεRI-mediated release of inflammatory mediators. Activation of various signaling pathways in mast cells results in changes in cell morphology, adhesion to substrate, exocytosis, and migration. Reorganization of cytoskeleton is pivotal in all these processes. Cytoskeletal proteins also play an important role in initial stages of FcεRI and other surface receptors induced triggering. Highly dynamic microtubules formed by αβ-tubulin dimers as well as microfilaments build up from polymerized actin are affected in activated cells by kinases/phosphatases, Rho GTPases and changes in concentration of cytosolic Ca2+. Also important are nucleation proteins; the γ-tubulin complexes in case of microtubules or Arp 2/3 complex with its nucleation promoting factors and formins in case of microfilaments. The dynamic nature of microtubules and microfilaments in activated cells depends on many associated/regulatory proteins. Changes in rigidity of activated mast cells reflect changes in intermediate filaments build up from vimentin. This review offers a critical appraisal of current knowledge on the role of cytoskeleton in mast cells signaling. PMID:22654883

  9. Refinement of treatment strategies in ex vivo T-cell-depleted haploidentical SCT for pediatric patients.

    PubMed

    Im, H J; Koh, K N; Suh, J K; Lee, S W; Choi, E S; Jang, S; Kwon, S W; Park, C-J; Seo, J J

    2015-02-01

    We evaluated the feasibility of T-cell-depleted haploidentical hematopoietic SCT (HHCT) in pediatric patients. Between July 2008 and January 2013, 28 patients underwent ex vivo T-cell-depleted HHCT; 9 had hematologic malignancy, 18 had nonmalignant hematologic disease, and 1 had refractory neuroblastoma. Twenty-six patients achieved neutrophil engraftment at a median of 11 days (range, 9-15 days). Two patients failed to achieve primary engraftment and five experienced graft rejection after primary engraftment. These seven patients achieved stable engraftment after a second HHCT. The cumulative incidences (CIs) of⩾grade II and⩾grade III acute GVHD were 33.3% and 14.3%, respectively, and the 1-year CI of extensive chronic GVHD was 11.1%. Four patients died of non-relapse-related causes (two of CMV disease, one of encephalopathy and one of autoimmune hemolytic anemia) and one of leukemia relapse. Non-relapse mortality at 100 days, 1 year and 2 years was 0.0%, 10.7% and 14.3%, respectively. At a median follow-up of 32.8 months (range, 17.0-72.5 months), the 2-year OS was 82.1%. OSs for nonmalignant diseases and malignant diseases were 94.4% and 60.0%, respectively (P=0.019). Thus, HHCT is a realistic alternative for patients with malignant or nonmalignant diseases who lack a suitable donor.

  10. Cumulative mechanisms of lymphoid tissue fibrosis and T cell depletion in HIV-1 and SIV infections

    PubMed Central

    Zeng, Ming; Smith, Anthony J.; Wietgrefe, Stephen W.; Southern, Peter J.; Schacker, Timothy W.; Reilly, Cavan S.; Estes, Jacob D.; Burton, Gregory F.; Silvestri, Guido; Lifson, Jeffrey D.; Carlis, John V.; Haase, Ashley T.

    2011-01-01

    The hallmark of HIV-1 and SIV infections is CD4+ T cell depletion. Both direct cell killing and indirect mechanisms related to immune activation have been suggested to cause the depletion of T cells. We have now identified a mechanism by which immune activation-induced fibrosis of lymphoid tissues leads to depletion of naive T cells in HIV-1 infected patients and SIV-infected rhesus macaques. The T regulatory cell response to immune activation increased procollagen production and subsequent deposition as fibrils via the TGF-β1 signaling pathway and chitinase 3-like-1 activity in fibroblasts in lymphoid tissues from patients infected with HIV-1. Collagen deposition restricted T cell access to the survival factor IL-7 on the fibroblastic reticular cell (FRC) network, resulting in apoptosis and depletion of T cells, which, in turn, removed a major source of lymphotoxin-β, a survival factor for FRCs during SIV infection in rhesus macaques. The resulting loss of FRCs and the loss of IL-7 produced by FRCs may thus perpetuate a vicious cycle of depletion of T cells and the FRC network. Because this process is cumulative, early treatment and antifibrotic therapies may offer approaches to moderate T cell depletion and improve immune reconstitution during HIV-1 infection. PMID:21393864

  11. Nonclinical evaluation of the potential for mast cell activation by an erythropoietin analog

    SciTech Connect

    Weaver, James L.

    2015-09-15

    The erythropoietin analog peginesatide was withdrawn from marketing due to unexpected severe anaphylactic reactions associated with administration of the multi-use formulation. The adverse events occurred rapidly following the first ever administration of the drug with most affected patients becoming symptomatic in less than 30 min. This is most consistent with an anaphylactoid reaction due to direct activation of mast cells. Laboratory evaluation was undertaken using rat peritoneal mast cells as the model system. Initial studies showed that high concentrations of the formulated drug as well as formulated vehicle alone could cause mast cell degranulation as measured by histamine release. The purified active drug was not able to cause histamine release whereas the vehicle filtrate and lab created drug vehicle were equally potent at causing histamine release. Individual formulations of vehicle leaving one component out showed that histamine release was due to phenol. Dose response studies with phenol showed a very sharp dose response curve that was similar in three buffer systems. Cellular analysis by flow cytometry showed that the histamine release was not due to cell death, and that changes in light scatter parameters consistent with degranulation were rapidly observed. Limited testing with primary human mast cells showed a similar dose response of histamine release with exposure to phenol. To provide in vivo confirmation, rats were injected with vehicle formulated with various concentrations of phenol via a jugular vein cannula. Significant release of histamine was detected in blood samples taken 2 min after dosing at the highest concentrations tested. - Highlights: • Peginesatide caused severe anaphylactoid reactions in 0.2% of patients. • Both formulated drug and vehicle cause degranulation of rat mast cells. • Phenol was identified as the vehicle component causing degranulation. • Human mast cells show similar dose response to phenol as rat mast cells

  12. 30 CFR 56.7004 - Drill mast.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Drill mast. 56.7004 Section 56.7004 Mineral... HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES Drilling and Rotary Jet Piercing Drilling § 56.7004 Drill mast. Persons shall not be on a mast while the drill-bit is in operation...

  13. 30 CFR 56.7004 - Drill mast.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Drill mast. 56.7004 Section 56.7004 Mineral... HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES Drilling and Rotary Jet Piercing Drilling § 56.7004 Drill mast. Persons shall not be on a mast while the drill-bit is in operation...

  14. 30 CFR 56.7004 - Drill mast.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Drill mast. 56.7004 Section 56.7004 Mineral... HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES Drilling and Rotary Jet Piercing Drilling § 56.7004 Drill mast. Persons shall not be on a mast while the drill-bit is in operation...

  15. 30 CFR 56.7004 - Drill mast.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Drill mast. 56.7004 Section 56.7004 Mineral... HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES Drilling and Rotary Jet Piercing Drilling § 56.7004 Drill mast. Persons shall not be on a mast while the drill-bit is in operation...

  16. 30 CFR 57.7004 - Drill mast.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Drill mast. 57.7004 Section 57.7004 Mineral... HEALTH SAFETY AND HEALTH STANDARDS-UNDERGROUND METAL AND NONMETAL MINES Drilling and Rotary Jet Piercing Drilling-Surface Only § 57.7004 Drill mast. Persons shall not be on a mast while the drill-bit is...

  17. 30 CFR 57.7004 - Drill mast.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Drill mast. 57.7004 Section 57.7004 Mineral... HEALTH SAFETY AND HEALTH STANDARDS-UNDERGROUND METAL AND NONMETAL MINES Drilling and Rotary Jet Piercing Drilling-Surface Only § 57.7004 Drill mast. Persons shall not be on a mast while the drill-bit is...

  18. 30 CFR 57.7004 - Drill mast.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Drill mast. 57.7004 Section 57.7004 Mineral... HEALTH SAFETY AND HEALTH STANDARDS-UNDERGROUND METAL AND NONMETAL MINES Drilling and Rotary Jet Piercing Drilling-Surface Only § 57.7004 Drill mast. Persons shall not be on a mast while the drill-bit is...

  19. 30 CFR 57.7004 - Drill mast.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Drill mast. 57.7004 Section 57.7004 Mineral... HEALTH SAFETY AND HEALTH STANDARDS-UNDERGROUND METAL AND NONMETAL MINES Drilling and Rotary Jet Piercing Drilling-Surface Only § 57.7004 Drill mast. Persons shall not be on a mast while the drill-bit is...

  20. 30 CFR 57.7004 - Drill mast.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Drill mast. 57.7004 Section 57.7004 Mineral... HEALTH SAFETY AND HEALTH STANDARDS-UNDERGROUND METAL AND NONMETAL MINES Drilling and Rotary Jet Piercing Drilling-Surface Only § 57.7004 Drill mast. Persons shall not be on a mast while the drill-bit is...

  1. 30 CFR 56.7004 - Drill mast.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Drill mast. 56.7004 Section 56.7004 Mineral... HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES Drilling and Rotary Jet Piercing Drilling § 56.7004 Drill mast. Persons shall not be on a mast while the drill-bit is in operation...

  2. Thyroid status affects number and localization of thyroid hormone receptor expressing mast cells in bone marrow.

    PubMed

    Siebler, T; Robson, H; Bromley, M; Stevens, D A; Shalet, S M; Williams, G R

    2002-01-01

    Thyroid hormone (T(3)) plays a key role in endochondral ossification. The process relies on the coordinated synthesis and degradation of cartilage matrix and is disrupted in juvenile hypothyroidism, leading to abnormal skeletal development. Mast cells synthesize and store matrix-degrading enzymes. We examined whether thyroid status influences skeletal mast cell distribution in growing rats to determine whether they might modulate the actions of T(3) in bone. Tibiae were collected for histological, histochemical, immunohistochemical, and immunofluorescence analysis. Mast cells were increased throughout the bone marrow in hypothyroid rats compared with euthyroid, thyrotoxic, and hypothyroid-thyroxine replaced animals. Large numbers were present in metaphyseal marrow adjacent to the growth plate in hypothyroid animals and cells were distributed evenly throughout the marrow. Very few mast cells were present in metaphyseal marrow in other groups, but their numbers increased with increasing distance from the growth plate. T(3) receptor alpha1 (TRalpha1) was expressed in the nucleus and cytoplasm of skeletal mast cells, whereas TRalpha2 and TRbeta1 were restricted to the cytoplasm. Localization of TRs was not affected by altered thyroid status. Thus, disrupted endochondral ossification in hypothyroidism may be mediated in part by skeletal mast cells, which express TR proteins and may function as T(3) target cells.

  3. Preservation of the secretory response of peritoneal mast cells in the absence of extracellular calcium.

    PubMed

    Bronner, C; Gies, J P; Vallé, A; Landry, Y

    1987-12-01

    The transfer of rat peritoneal mast cells from balanced salt solution to calcium-free buffer led to a time-dependent decrease in their response to compound 48/80 and to ionophore A23187. The concomittant absence of potassium from the calcium-free buffer enabled the mast cells to retain their secretory response. The increase in potassium level, with a parallel decrease in sodium to maintain osmolarity, led to a slight potentiation of the response to 48/80 and to a large but transient potentiation of the response to A23187. Mast cells can be considered nonexcitable. The apparent dependency upon extracellular calcium of mast cell secretory responses might be related to the presumed tight equilibrium between endoplasmic reticulum calcium stores and extracellular calcium. The control of this equilibrium by transmembrane gradients of monovalent ions is proposed. PMID:2446099

  4. Estrogen Inhibits Mast Cell Chymase Release to Prevent Pressure Overload-Induced Adverse Cardiac Remodeling

    PubMed Central

    Li, Jianping; Jubair, Shaiban; Janicki, Joseph S.

    2014-01-01

    Estrogen regulation of myocardial chymase and chymase effects on cardiac remodeling are unknown. To test the hypothesis that estrogen prevents pressure overload-induced adverse cardiac remodeling by inhibiting mast cell chymase release, transverse aortic constriction or sham surgery was performed in 7-week-old intact and ovariectomized rats. Three days prior to creating the constriction, additional groups of ovariectomized rats began receiving 17β-Estradiol, a chymase inhibitor, or a mast cell stabilizer. Left ventricular function, cardiomyocyte size, collagen volume fraction, mast cell density and degranulation, and myocardial and plasma chymase levels were assessed 18 days post-surgery. Aortic constriction resulted in ventricular hypertrophy in intact and ovariectomized groups while collagen volume fraction was increased only in ovariectomized rats. Chymase protein content was increased by aortic constriction in the intact and ovariectomized groups with the magnitude of the increase being greater in ovariectomized rats. Mast cell density and degranulation, plasma chymase levels and myocardial active transforming growth factor- 1 levels were increased by aortic constriction only in ovariectomized rats. Estrogen replacement markedly attenuated the constriction-increased myocardial chymase, mast cell density and degranulation, plasma chymase and myocardial active transforming growth factor- 1 as well as prevented ventricular hypertrophy and increased collagen volume fraction. Chymostatin attenuated the aortic constriction induced ventricular hypertrophy and collagen volume fraction in the ovariectomized rats similar to that achieved by estrogen replacement. Nedocromil yielded similar effects except for the reduction of chymase content. We conclude that the estrogen-inhibited release of mast cell chymase is responsible for the cardioprotection against transverse aortic constriction-induced adverse cardiac remodeling. PMID:25403608

  5. Ets Factors Regulate Neural Stem Cell Depletion and Gliogenesis in Ras Pathway Glioma.

    PubMed

    Breunig, Joshua J; Levy, Rachelle; Antonuk, C Danielle; Molina, Jessica; Dutra-Clarke, Marina; Park, Hannah; Akhtar, Aslam Abbasi; Kim, Gi Bum; Hu, Xin; Bannykh, Serguei I; Verhaak, Roel G W; Danielpour, Moise

    2015-07-14

    As the list of putative driver mutations in glioma grows, we are just beginning to elucidate the effects of dysregulated developmental signaling pathways on the transformation of neural cells. We have employed a postnatal, mosaic, autochthonous glioma model that captures the first hours and days of gliomagenesis in more resolution than conventional genetically engineered mouse models of cancer. We provide evidence that disruption of the Nf1-Ras pathway in the ventricular zone at multiple signaling nodes uniformly results in rapid neural stem cell depletion, progenitor hyperproliferation, and gliogenic lineage restriction. Abolishing Ets subfamily activity, which is upregulated downstream of Ras, rescues these phenotypes and blocks glioma initiation. Thus, the Nf1-Ras-Ets axis might be one of the select molecular pathways that are perturbed for initiation and maintenance in glioma.

  6. Lipid Rafts in Mast Cell Biology

    PubMed Central

    Silveira e Souza, Adriana Maria Mariano; Mazucato, Vivian Marino; Jamur, Maria Célia; Oliver, Constance

    2011-01-01

    Mast cells have long been recognized to have a direct and critical role in allergic and inflammatory reactions. In allergic diseases, these cells exert both local and systemic responses, including allergic rhinitis and anaphylaxis. Mast cell mediators are also related to many chronic inflammatory conditions. Besides the roles in pathological conditions, the biological functions of mast cells include roles in innate immunity, involvement in host defense mechanisms against parasites, immunomodulation of the immune system, tissue repair, and angiogenesis. Despite their growing significance in physiological and pathological conditions, much still remains to be learned about mast cell biology. This paper presents evidence that lipid rafts or raft components modulate many of the biological processes in mast cells, such as degranulation and endocytosis, play a role in mast cell development and recruitment, and contribute to the overall preservation of mast cell structure and organization. PMID:21490812

  7. Mast Cells in Allergic Diseases and Mastocytosis

    PubMed Central

    Marquardt, Diana L.; Wasserman, Stephen I.

    1982-01-01

    Mast cells with their stores of vasoactive and chemotactic mediators are central to the pathogenesis of allergic diseases. The cross-linking of receptorbound IgE molecules on the surface of mast cells initiates a complex chain of events, including calcium ion influx, phospholipid methylation and turnover and cyclic nucleotide metabolism, ultimately resulting in the release of mediators of immediate hypersensitivity. These mast cell mediators are important in smooth muscle reactivity, in the recruitment of eosinophilic and neutrophilic leukocytes and in the generation of secondary chemical mediators. Histologic evidence of mast cell degranulation, biochemical evidence of mast cell mediators in blood and tissues and clinical evidence of signs and symptoms reproducible by these mediators have strongly supported the crucial role of mast cells in asthma, urticaria, anaphylaxis, rhinitis and mastocytosis. Because of their unique location at host environment interfaces, mast cells may both participate in allergic diseases and promote homeostasis. ImagesFigure 1.Figure 2.Figure 3. PMID:6293204

  8. New treatments for SLE: cell-depleting and anti-cytokine therapies.

    PubMed

    Anolik, Jennifer H; Aringer, Martin

    2005-10-01

    Although systemic lupus erythematosus (SLE) is indeed a complex autoimmune disease, recent advances in our understanding of lupus pathogenesis have suggested new, targeted approaches to therapy. The purpose of this review is to discuss the underlying scientific rationale and results of first clinical studies of new treatment approaches to SLE, with a focus on cell-depleting therapies and cytokine blockade. It has become clear that the B lymphocyte plays a key role in disease pathogenesis by both autoantibody-dependent and autoantibody-independent mechanisms. Additionally, aberrant interactions between B and T cells are critical to disease emergence and progression. New agents that directly target immune cells abnormal in SLE include the B-cell depleting or modulating antibodies, rituximab (anti-CD20) and epratuzumab (anti-CD22) and the anti-dsDNA tolerogen LJP394. Another promising approach has been to block co-stimulatory interactions between T and B cells, for example by inhibiting the CD40-CD40 ligand pathway with anti-CD40 ligand monoclonal antibody or the B7 pathway with CTLA-4Ig. Immune cells can also be manipulated indirectly through cytokine effects. For B cells, anti-BAFF (B-cell activation factor of the tumor necrosis family) provides an example of this approach. Other, more pleiotropic cytokines can likewise be blocked in SLE. In addition to the blockade of interleukin-10 (IL-10), the first anti-cytokine approach examined, it is mainly anti-tumor necrosis factor therapy that has come into focus, holding promise for some patients with lupus nephritis. The majority of the available data on these new treatment approaches stems from open-label trials, but controlled trials are under way. Moreover, many additional cytokines, such as interleukin (IL)-6, IL-18, and the type I interferons, represent interesting future targets.

  9. Targeted Type 2 Alveolar Cell Depletion. A Dynamic Functional Model for Lung Injury Repair.

    PubMed

    Garcia, Orquidea; Hiatt, Michael J; Lundin, Amber; Lee, Jooeun; Reddy, Raghava; Navarro, Sonia; Kikuchi, Alex; Driscoll, Barbara

    2016-03-01

    Type 2 alveolar epithelial cells (AEC2) are regarded as the progenitor population of the alveolus responsible for injury repair and homeostatic maintenance. Depletion of this population is hypothesized to underlie various lung pathologies. Current models of lung injury rely on either uncontrolled, nonspecific destruction of alveolar epithelia or on targeted, nontitratable levels of fixed AEC2 ablation. We hypothesized that discrete levels of AEC2 ablation would trigger stereotypical and informative patterns of repair. To this end, we created a transgenic mouse model in which the surfactant protein-C promoter drives expression of a mutant SR39TK herpes simplex virus-1 thymidine kinase specifically in AEC2. Because of the sensitivity of SR39TK, low doses of ganciclovir can be administered to these animals to induce dose-dependent AEC2 depletion ranging from mild (50%) to lethal (82%) levels. We demonstrate that specific levels of AEC2 depletion cause altered expression patterns of apoptosis and repair proteins in surviving AEC2 as well as distinct changes in distal lung morphology, pulmonary function, collagen deposition, and expression of remodeling proteins in whole lung that persist for up to 60 days. We believe SPCTK mice demonstrate the utility of cell-specific expression of the SR39TK transgene for exerting fine control of target cell depletion. Our data demonstrate, for the first time, that specific levels of type 2 alveolar epithelial cell depletion produce characteristic injury repair outcomes. Most importantly, use of these mice will contribute to a better understanding of the role of AEC2 in the initiation of, and response to, lung injury.

  10. Anti-tetanus toxoid antibody production after mismatched T cell-depleted bone marrow transplantation.

    PubMed

    Benkerrou, M; Wara, D W; Elder, M; Dror, Y; Merino, A; Colombe, B W; Garovoy, M; Cowan, M J

    1994-03-01

    We explored B-cell function after tetanus toxoid (TT) immunization in 12 children with severe combined immunodeficiency disease or leukemia who were long-term survivors of an HLA-matched sibling or haplocompatible T cell-depleted parental bone marrow transplant (BMT), 10 of their healthy donors, and 13 normal controls. Specific in vivo and in vitro anti-TT antibody (Ab) production were measured by ELISA. We studied donors' and recipients' peripheral blood mononuclear cells (PBMC) and mixed E- (non-T cells) and E+ cells (T cells) spontaneously and after stimulation by TT in the absence or presence of interleukin-2 (IL-2), IL-4, and IL-6. Five of the 12 patients and all donors and controls responded with in vivo anti-TT Ab. In vitro anti-TT Ab production correlated with the in vivo response. All seven of the nonresponders were either fully engrafted or mixed chimeras (donor T cells but autologous B cells and monocytes). We could not identify a T-cell defect in four of the five nonresponders who were tested. In contrast, E- cells from three of three responders cooperated with fresh donor E+ cells even when they shared only one HLA haplotype. In three of seven nonresponders, in vitro anti-TT Ab production was restored after the addition of IL-4 or IL-6 but not IL-2. Our results suggest that the humoral immunodeficiency that exists post mismatched T cell-depleted BMT is either a B-cell, a monocyte, or a B-cell/T-cell cooperation defect which, in some patients, may be correctible with the addition of a cytokine. Also, it is not necessary to engraft donor B cells to achieve normal antibody responses and the ability to respond does not appear to correlate with pretransplant chemotherapy.

  11. Role of mast cell in the late phase of contact hypersensitivity induced by trimellitic anhydride

    PubMed Central

    Chai, Ok Hee

    2015-01-01

    Mast cells are known as effector cells of IgE-mediated allergic responses, but role of mast cells in contact hypersensitivity (CHS) has been considered controversial. In this study, we investigated role of mast cell in trimellitic anhydride (TMA)-induced CHS. The mice were sensitized to TMA on the back and repeatedly challenged with TMA on the left ear at 1-week intervals. The ear after challenge showed biphasic responses. The repetition of TMA challenge shifted in time course of ear response and enlarged the extent of early and late phase reactions in proportion to the frequency of TMA challenges in C57BL/6 mice. In late phase reaction, peak of ear response by single challenge showed at 24 hours after challenge, but the peak by repeat challenges at 8 hours after the last challenge. Number of mast cells and eosinophils per unit area increased in proportion to frequency of TMA challenges. However, mast cell-deficient WBB6F1/J-KitW/KitW-v mice developed the late phase reaction without the early phase reaction. The repetition of TMA challenge shifted in time course of ear response and enlarged the extent of ear response and the infiltration of eosinophils. The magnitude of these responses observed according to the frequency of the TMA challenge in mast cell-deficient WBB6F1/J-KitW/KitW-v mice was significantly lower than that in C57BL/6 mice. Also TMA elicited mast cell degranulation and histamine release from rat peritoneal mast cells in a concentration-dependent manner. Conclusively, TMA induces the early and late phase reactions in CHS, and mast cells may be required for TMA-induced CHS. PMID:26770872

  12. Stimulation of mast cells leads to cholesterol accumulation in macrophages in vitro by a mast cell granule-mediated uptake of low density lipoprotein

    SciTech Connect

    Kokkonen, J.O.; Kovanen, P.T.

    1987-04-01

    The uptake of low density lipoprotein (LDL) by cultured mouse macrophages was markedly promoted by isolated rat mast cell granules present in the culture medium. The granule-mediated uptake of /sup 125/I-LDL enhanced the rate of cholesteryl ester synthesis in the macrophages, the result being accumulation of cholesteryl esters in these cells. Binding of LDL to the granules was essential for the granule-mediated uptake of LDL by macrophages, for the uptake process was prevented by treating the granules with avidin or protamine chloride or by treating LDL with 1,2-cyclohexanedione, all of which inhibit the binding of LDL to the granules. Inhibition of granule phagocytosis by the macrophages with cytochalasin B also abolished the granule-mediated uptake of LDL. Finally, mouse macrophage monolayers and LDL were incubated in the presence of isolated rat serosal mast cells. Stimulation of the mast cells with compound 48/80, a degranulating agent, resulted in dose-dependent release of secretory granules from the mast cells and a parallel increase in /sup 14/C cholesteryl ester synthesis in the macrophages. The results show that, in this in vitro model, the sequence of events leading to accumulation of cholesteryl esters in macrophages involves initial stimulation of mast cells, subsequent release of their secretory granules, binding of LDL to the exocytosed granules, and, finally, phagocytosis of the LDL-containing granules by macrophages.

  13. Acute Stress-Induced Changes in Follicular Dermal Papilla Cells and Mobilization of Mast Cells: Implications for Hair Growth

    PubMed Central

    Shin, Hyoseung; Choi, Soon-Jin; Cho, A-Ri; Kim, Dong Young; Kim, Kyu Han

    2016-01-01

    Background Stress is a known cause of hair loss in many species. Objective In this study, we investigated the role of acute stress on hair growth using a rat model. Methods Rats were immobilized for 24 hours and blood samples, and skin biopsies were taken. The effect of stress-serum on the in vitro proliferation of rat and human dermal papilla cells (hDPCs), as well as serum cortisol and corticotropin-releasing hormone levels, were measured. Mast cell staining was performed on the biopsied tissue. In addition, Western blot and quantitative real time polymerase chain reaction were used to assess mast cell tryptase and cytokine expression, respectively in rat skin biopsies. Results Stress-serum treatment reduced significantly the number of viable hDPCs and arrested the cell cycle in the G1 phase, compared to serum from unrestrained rats (p<0.05, respectively). Moreover, restrained rats had significantly higher levels of cortisol in serum than unrestrained rats (p<0.01). Acute stress serum increased mast cell numbers and mast cell tryptase expression, as well as inducing interleukin (IL)-6 and IL-1β up-regulation. Conclusion These results suggest that acute stress also has an inhibitory effect on hair growth via cortisol release in addition to substance P-mast cell pathway. PMID:27746640

  14. Role of mast cells in tumor growth.

    PubMed

    Conti, Pio; Castellani, Maria L; Kempuraj, Durasamy; Salini, Vincenzo; Vecchiet, Jacopo; Tetè, Stefano; Mastrangelo, Filiberto; Perrella, Alessandro; De Lutiis, Maria Anna; Tagen, Michael; Theoharides, Theoharis C

    2007-01-01

    The growth of malignant tumors is determined in large part by the proliferative capacity of the tumor cells. Clinical observations and animal experiments have established that tumor cells elicit immune responses. Histopathologic studies show that many tumors are surrounded by mononuclear cell and mast cell infiltrates. Mast cells are ubiquitous in the body and are critical for allergic reactions. Increasing evidence indicates that mast cells secrete proinflammatory cytokines and are involved in neuro-inflammatory processes and cancer. Mast cells accumulate in the stroma surrounding certain tumors, especially mammary adenocarcinoma, and the molecules they secrete can benefit the tumor. However, mast cells can also increase at the site of tumor growth and participate in tumor rejection. Mast cells may be recruited by tumor-derived chemoattractants and selectively secrete molecules such as growth factors, histamine, heparin, VEGF, and IL-8, as well as proteases that permit the formation of new blood vessels and metastases. Tumor mast cell intersections play regulatory and modulatory roles affecting various aspects of tumor growth. Discovery of these new roles of mast cells further complicates the understanding of tumor growth. This review focuses on the strategic importance of mast cells to the progression of tumors, and proposes a revised immune effector mechanism of mast cell involvement in tumor growth. PMID:18000287

  15. Genitourinary mast cells and survival.

    PubMed

    Theoharides, Theoharis C; Stewart, Julia M

    2015-10-01

    Mast cells (MCs) are ubiquitous in the body, but they have historically been associated with allergies, and most recently with regulation of immunity and inflammation. However, it remains a puzzle why so many MCs are located in the diencephalon, which regulates emotions and in the genitourinary tract, including the bladder, prostate, penis, vagina and uterus that hardly ever get allergic reactions. A number of papers have reported that MCs have estrogen, gonadotropin and corticotropin-releasing hormone (CRH) receptors. Moreover, animal experiments have shown that diencephalic MCs increase in number during courting in doves. We had reported that allergic stimulation of nasal MCs leads to hypothalamic-pituitary adrenal (HPA) activation. Interestingly, anecdotal information indicates that female patients with mastocytosis or mast cell activation syndrome may have increased libido. Preliminary evidence also suggests that MCs may have olfactory receptors. MCs may, therefore, have been retained phylogenetically not only to "smell danger", but to promote survival and procreation. PMID:26813805

  16. The human lung mast cell.

    PubMed Central

    Wasserman, S I

    1984-01-01

    Mast cells are present in human lung tissue, pulmonary epithelium, and free in the bronchial lumen. By virtue of their location and their possession of specific receptors for IgE and complement fragments, these cells are sentinel cells in host defense. The preformed granular mediators and newly generated lipid mediators liberated upon activation of mast cells by a variety of secretagogues supply potent vasoactive-spasmogenic mediators, chemotactic factors, active enzymes, and proteoglycans to the local environment. These factors acting together induce an immediate response manifest as edema, smooth muscle constriction, mucus production, and cough. Later these mediators and those provided from plasma and leukocytes generate a tissue infiltrate of inflammatory cells and more prolonged vasoactive-bronchospastic responses. Acute and prolonged responses may be homeostatic and provide for defense of the host, but if excessive in degree or duration may provide a chronic inflammatory substrate upon which such disorders as asthma and pulmonary fibrosis may ensue. PMID:6428878

  17. Genitourinary mast cells and survival

    PubMed Central

    Stewart, Julia M.

    2015-01-01

    Mast cells (MCs) are ubiquitous in the body, but they have historically been associated with allergies, and most recently with regulation of immunity and inflammation. However, it remains a puzzle why so many MCs are located in the diencephalon, which regulates emotions and in the genitourinary tract, including the bladder, prostate, penis, vagina and uterus that hardly ever get allergic reactions. A number of papers have reported that MCs have estrogen, gonadotropin and corticotropin-releasing hormone (CRH) receptors. Moreover, animal experiments have shown that diencephalic MCs increase in number during courting in doves. We had reported that allergic stimulation of nasal MCs leads to hypothalamic-pituitary adrenal (HPA) activation. Interestingly, anecdotal information indicates that female patients with mastocytosis or mast cell activation syndrome may have increased libido. Preliminary evidence also suggests that MCs may have olfactory receptors. MCs may, therefore, have been retained phylogenetically not only to “smell danger”, but to promote survival and procreation. PMID:26813805

  18. Changes in mast cells and in permeability of mesenteric microvessels under the effect of immobilization and electrostimulation

    NASA Technical Reports Server (NTRS)

    Gorizontova, M. P.

    1980-01-01

    It was shown that a reduction in the amount of mast cells in the mesentery and an increase in their degranulation was accompanied by an increase in vascular permeability of rat mesentery. It is supposed that immobilization and electrostimulation causing degranulation of mast cells prompted histamine and serotonin release from them, thus increasing the permeability of the venular portion of the microvascular bed. Prophylactic use of esculamin preparation with P-vitaminic activity decreased mast cell degranulation, which apparently prolonged the release of histamine and serotonin from them and normalized vascular permeability.

  19. Ripe fruit of Rubus coreanus inhibits mast cell-mediated allergic inflammation.

    PubMed

    Kim, Hui-Hun; Choi, Phil Hyung; Yoo, Jin-Su; Jeon, Hoon; Chae, Byeong-Suk; Park, Jeong-Suk; Kim, Sang-Hyun; Shin, Tae-Yong

    2012-02-01

    In this study, we investigated the effect of a water extract of the ripe fruits of Rubus coreanus Miq. (Rosaceae) (RFRC) on mast cell-mediated allergic inflammation and studied the possible mechanism of action. Mast cell-mediated allergic disease is involved in many diseases such as anaphylaxis, rhinitis, asthma and atopic dermatitis. RFRC dose-dependently inhibited compound 48/80-induced systemic anaphylaxis and serum histamine release in mice. RFRC reduced the immunoglobulin E (IgE)-mediated local allergic reaction, passive cutaneous anaphylaxis. RFRC attenuated histamine release from rat peritoneal mast cells and human mast cells by the reduction of intracellular calcium. RFRC decreased the phorbol 12-myristate 13-acetate (PMA) and the calcium ionophore A23187 (PMACI)-stimulated expression and secretion of pro-inflammatory cytokines in human mast cells. The inhibitory effect of RFRC on cytokine production was nuclear factor (NF)-κB- and mitogen-activated protein kinase (MAPK)-dependent. In addition, RFRC suppressed the activation of caspase-1. Our findings provide evidence that RFRC inhibits mast cell-derived allergic inflammatory reactions, and for the involvement of calcium, NF-κB, MAPKs and caspase-1 in these effects. Furthermore, in vivo and in vitro anti-allergic inflammatory effects of RFRC provide affirmative proof of a possible therapeutic application of this agent in allergic inflammatory diseases. PMID:22075758

  20. Telomerase abrogates aneuploidy-induced telomere replication stress, senescence and cell depletion

    PubMed Central

    Meena, Jitendra K; Cerutti, Aurora; Beichler, Christine; Morita, Yohei; Bruhn, Christopher; Kumar, Mukesh; Kraus, Johann M; Speicher, Michael R; Wang, Zhao-Qi; Kestler, Hans A; d’Adda di Fagagna, Fabrizio; Günes, Cagatay; Rudolph, Karl Lenhard

    2015-01-01

    The causal role of aneuploidy in cancer initiation remains under debate since mutations of euploidy-controlling genes reduce cell fitness but aneuploidy strongly associates with human cancers. Telomerase activation allows immortal growth by stabilizing telomere length, but its role in aneuploidy survival has not been characterized. Here, we analyze the response of primary human cells and murine hematopoietic stem cells (HSCs) to aneuploidy induction and the role of telomeres and the telomerase in this process. The study shows that aneuploidy induces replication stress at telomeres leading to telomeric DNA damage and p53 activation. This results in p53/Rb-dependent, premature senescence of human fibroblast, and in the depletion of hematopoietic cells in telomerase-deficient mice. Endogenous telomerase expression in HSCs and enforced expression of telomerase in human fibroblasts are sufficient to abrogate aneuploidy-induced replication stress at telomeres and the consequent induction of premature senescence and hematopoietic cell depletion. Together, these results identify telomerase as an aneuploidy survival factor in mammalian cells based on its capacity to alleviate telomere replication stress in response to aneuploidy induction. PMID:25820263

  1. Autoantigen-specific B-cell depletion overcomes failed immune tolerance in type 1 diabetes.

    PubMed

    Henry, Rachel A; Kendall, Peggy L; Thomas, James W

    2012-08-01

    Eliminating autoantigen-specific B cells is an attractive alternative to global B-cell depletion for autoimmune disease treatment. To identify the potential for targeting a key autoimmune B-cell specificity in type 1 diabetes, insulin-binding B cells were tracked within a polyclonal repertoire using heavy chain B-cell receptor (BCR) transgenic (VH125Tg) mice. Insulin-specific B cells are rare in the periphery of nonautoimmune VH125Tg/C57BL/6 mice and WT/NOD autoimmune mice, whereas they clearly populate 1% of mature B-cell subsets in VH125Tg/NOD mice. Autoantigen upregulates CD86 in anti-insulin B cells, suggesting they are competent to interact with T cells. Endogenous insulin occupies anti-insulin BCR beginning with antigen commitment in bone marrow parenchyma, as identified by a second anti-insulin monoclonal antibody. Administration of this monoclonal antibody selectively eliminates insulin-reactive B cells in vivo and prevents disease in WT/NOD mice. Unexpectedly, developing B cells are less amenable to depletion, despite increased BCR sensitivity. These findings exemplify how a critical type 1 diabetes B-cell specificity escapes immune tolerance checkpoints. Disease liability is corrected by eliminating this B-cell specificity, providing proof of concept for a novel therapeutic approach for autoimmune disease. PMID:22698916

  2. Cell death by pyroptosis drives CD4 T-cell depletion in HIV-1 infection

    NASA Astrophysics Data System (ADS)

    Doitsh, Gilad; Galloway, Nicole L. K.; Geng, Xin; Yang, Zhiyuan; Monroe, Kathryn M.; Zepeda, Orlando; Hunt, Peter W.; Hatano, Hiroyu; Sowinski, Stefanie; Muñoz-Arias, Isa; Greene, Warner C.

    2014-01-01

    The pathway causing CD4 T-cell death in HIV-infected hosts remains poorly understood although apoptosis has been proposed as a key mechanism. We now show that caspase-3-mediated apoptosis accounts for the death of only a small fraction of CD4 T cells corresponding to those that are both activated and productively infected. The remaining over 95% of quiescent lymphoid CD4 T cells die by caspase-1-mediated pyroptosis triggered by abortive viral infection. Pyroptosis corresponds to an intensely inflammatory form of programmed cell death in which cytoplasmic contents and pro-inflammatory cytokines, including IL-1β, are released. This death pathway thus links the two signature events in HIV infection--CD4 T-cell depletion and chronic inflammation--and creates a pathogenic vicious cycle in which dying CD4 T cells release inflammatory signals that attract more cells to die. This cycle can be broken by caspase 1 inhibitors shown to be safe in humans, raising the possibility of a new class of `anti-AIDS' therapeutics targeting the host rather than the virus.

  3. Identification of a lysophosphatidylserine receptor on mast cells.

    PubMed

    Sugo, Tsukasa; Tachimoto, Hiroshi; Chikatsu, Tomoko; Murakami, Yuko; Kikukawa, Yuhsuke; Sato, Shuji; Kikuchi, Kuniko; Nagi, Toshimi; Harada, Mioko; Ogi, Kazuhiro; Ebisawa, Motohiro; Mori, Masaaki

    2006-03-24

    Lysophosphatidyl-L-serine (lysoPS) is thought to be an immunological regulator because it dramatically augments the degranulation of rat peritoneal mast cells (RPMCs). This stimulatory effect may be mediated by a lysoPS receptor, but its molecule has not been identified yet. During a ligand fishing study for the orphan G-protein-coupled receptor 34 (GPR34), we found that lysoPS caused a dose-dependent inhibition of forskolin-stimulated cAMP accumulation in human GPR34-expressing Chinese hamster ovary (CHO/hGPR34) cells. The CHO/hGPR34 cells were unresponsive to other structurally related phospholipids examined. Quantitative real-time-PCR demonstrated that mRNAs of GPR34 are particularly abundant in mast cells. The effective lysoPS concentration for RPMC degranulation was similar to that required for GPR34 activation, and the structural requirement of lysoPS for RPMC degranulation was in good agreement with that observed in CHO/hGPR34 cells. These results suggest that GPR34 is the functional mast cell lysoPS receptor. PMID:16460680

  4. A comparative review of methods for T cell depletion in the prophylaxis of graft-versus-host disease.

    PubMed

    Hertenstein, B; Arseniev, L; Novotny, J; Ganser, A

    1998-02-01

    Graft-versus-host disease (GVHD) remains the major problem to be overcome in transplantation of allogeneic haemopoietic stem cells. Using immunosuppressive prophylaxis with cyclosporin and methotrexate, moderate to severe acute GVHD develops in approximately 45% of transplant recipients with an HLA-identical sibling donor and in >75% of patients from unrelated HLA-identical or partially matched related donors. The pathophysiology of GVHD is complex and still incompletely described. Experimental and clinical data indicate that GVHD is largely mediated by immunocompetent T cells in the donor stem cell graft which are reactive against recipient (host) tissues. Depletion of these immunocompetent T cells from the stem cell graft offers a way to effectively prevent GVHD. The first section of this review describes the technical principles of different methods of T cell depletion. The advantages, limitations and level of T cell depletion achievable by physical methods or by positive and negative immunoselection procedures using monoclonal antibodies are comprehensively discussed. A short section concentrates on technical problems in the enumeration of T cells in the context of depletion efficiency. In the section on clinical studies, the focus is on the efficacy of different T cell depletion methods in avoiding GVHD in different clinical settings. The various methods are compared in transplantation from HLA-identical and nonidentical siblings or matched unrelated donors. The major drawbacks of T cell depletion are discussed in detail. Failure of engraftment and graft rejection is a more frequent problem following T cell-depleted transplants, particularly with HLA nonidentical donor-recipient pairs. An increase in leukaemic relapse rate is seen in certain haematological malignancies, especially in chronic myeloid leukaemia. Delayed recovery of anti-infectious immunity occurs, leading to an increased incidence of cytomegalovirus and Epstein-Barr virus related problems. The

  5. The effect of B-cell depletion in the Theiler's model of multiple sclerosis.

    PubMed

    Gilli, Francesca; Li, Libin; Campbell, Sandra J; Anthony, Daniel C; Pachner, Andrew R

    2015-12-15

    B cell depletion (BCD) is being considered as a treatment for multiple sclerosis (MS), but there are many uncertainties surrounding the use of this therapy, such as its potential effect in individuals with concurrent viral infections. We sought to discover what effect BCD, induced by an anti-CD20 monoclonal antibody, would have on Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD). Mice were injected with the anti-CD20 monoclonal antibody 5D2, 14 days before or 14 days after infection with TMEV. Efficacy of depletion of B cells was assessed by flow cytometry of CD19(+) cells. Mouse disability was measured by Rotarod, viral load was measured by real time PCR for TMEV RNA. Binding and neutralizing antibody levels were determined in sera and CSF by ELISA, and in CNS by real time PCR for IgG RNA. Inflammation, microglial activation, axonal damage and demyelination were assessed using immunohistochemistry. 5D2-induced BCD was confirmed by demonstration of nearly absent CD19(+) cells in the blood and lymphoid tissue. Systemic and CNS antibody responses were suppressed during 5D2 treatment. Higher viral loads were detected in 5D2-treated mice than in controls, and the viral levels correlated negatively with IgG production in the brain. Overall, 5D2 caused worsening of the early encephalitis and faster progression of disability, as well as exacerbation of the pathology of TMEV-IDD at the end stage of the disease. These data indicate that BCD in humans might worsen CNS viral infections and might not improve disability accrual in MS. PMID:26671084

  6. Proinflammatory GM-CSF-producing B cells in multiple sclerosis and B cell depletion therapy.

    PubMed

    Li, Rui; Rezk, Ayman; Miyazaki, Yusei; Hilgenberg, Ellen; Touil, Hanane; Shen, Ping; Moore, Craig S; Michel, Laure; Althekair, Faisal; Rajasekharan, Sathy; Gommerman, Jennifer L; Prat, Alexandre; Fillatreau, Simon; Bar-Or, Amit

    2015-10-21

    B cells are not limited to producing protective antibodies; they also perform additional functions relevant to both health and disease. However, the relative contribution of functionally distinct B cell subsets in human disease, the signals that regulate the balance between such subsets, and which of these subsets underlie the benefits of B cell depletion therapy (BCDT) are only partially elucidated. We describe a proinflammatory, granulocyte macrophage-colony stimulating factor (GM-CSF)-expressing human memory B cell subset that is increased in frequency and more readily induced in multiple sclerosis (MS) patients compared to healthy controls. In vitro, GM-CSF-expressing B cells efficiently activated myeloid cells in a GM-CSF-dependent manner, and in vivo, BCDT resulted in a GM-CSF-dependent decrease in proinflammatory myeloid responses of MS patients. A signal transducer and activator of transcription 5 (STAT5)- and STAT6-dependent mechanism was required for B cell GM-CSF production and reciprocally regulated the generation of regulatory IL-10-expressing B cells. STAT5/6 signaling was enhanced in B cells of untreated MS patients compared with healthy controls, and B cells reemerging in patients after BCDT normalized their STAT5/6 signaling as well as their GM-CSF/IL-10 cytokine secretion ratios. The diminished proinflammatory myeloid cell responses observed after BCDT persisted even as new B cells reconstituted. These data implicate a proinflammatory B cell/myeloid cell axis in disease and underscore the rationale for selective targeting of distinct B cell populations in MS and other human autoimmune diseases. PMID:26491076

  7. The role of mast cells in cancers

    PubMed Central

    Maciel, Thiago T.; Moura, Ivan C.

    2015-01-01

    Mast cells are immune cells that accumulate in the tumors and their microenvironment during disease progression. Mast cells are armed with a wide array of receptors that sense environment modifications and, upon stimulation, they are able to secrete several biologically active factors involved in the modulation of tumor growth. For example, mast cells are able to secrete pro-angiogenic and growth factors but also pro- and anti-inflammatory mediators. Recent studies have allowed substantial progress in understanding the role of mast cells in tumorigenesis/disease progression but further studies are necessary to completely elucidate their impact in the pathophysiology of cancer. Here we review observations suggesting that mast cells could modulate tumor growth in humans. We also discuss the drawbacks related to observations from mast cell-deficient mouse models, which could have consequences in the determination of a potential causative relationship between mast cells and cancer. We believe that the understanding of the precise role of mast cells in tumor development and progression will be of critical importance for the development of new targeted therapies in human cancers. PMID:25705392

  8. Marshall Avionics Testbed System (MAST)

    NASA Technical Reports Server (NTRS)

    Smith, Wayne D.

    1989-01-01

    Work accomplished in the summer of 1989 in association with the NASA/ASEE Summer Faculty Research Fellowship Program at Marshall Space Flight Center is summarized. The project was aimed at developing detailed specifications for the Marshall Avionics System Testbed (MAST). This activity was to include the definition of the testbed requirements and the development of specifications for a set of standard network nodes for connecting the testbed to a variety of networks. The project was also to include developing a timetable for the design, implementation, programming and testing of the testbed. Specifications of both hardware and software components for the system were to be included.

  9. [Degranulation of skin mast cells caused by high frequency electromagnetic irradiation of low intensity].

    PubMed

    Popov, V I; Rogachevskiĭ, V V; Gapeev, A B; Khramov, R N; Fesenko, E E

    2001-01-01

    It was shown by light and electron microscopy that local exposure of the projection of the MC-8 lao-gun acupuncture point in rat pad to low-intensity (0.05 mW/cm2) extremely high-frequency (42.0 GHz) electromagnetic radiation caused a degranulation of derma mast cells. It was suggested that the response of skin mast cells is an important amplifying mechanism in the chain of events leading to a systemic response of the organism to low-intensity electromagnetic radiation.

  10. Identification of chondroitin sulfate E proteoglycans and heparin proteoglycans in the secretory granules of human lung mast cells

    SciTech Connect

    Stevens, R.L.; Austen, K.F. ); Fox, C.C.; Lichtenstein, L.M. )

    1988-04-01

    The predominant subclasses of mast cells in both the rat and the mouse can be distinguished from one another by their preferential synthesis of {sup 35}S-labeled proteoglycans that contain either heparin or oversulfated chondroitin sulfate glycosaminoglycans. Although ({sup 35}S)heparin proteoglycans have been isolated from human lung mast cells of 40-70% purity and from a skin biopsy specimen of a patient with urticaria pigmentosa, no highly sulfated chondroitin sulfate proteoglycan has been isolated from any enriched or highly purified population of human mast cells. The authors demonstrate that human lung mast cells of 96% purity incorporate ({sup 35}S)sulfate into separate heparin and chondroitin sulfate proteoglycans in an {approx}2:1 ratio. As assessed by HPLC of the chondroitinase ABC digests, the chondroitin ({sup 35}S)sulfate proteoglycans isolated from these human lung mast cells contain the same unusual chondroitin sulfate E disaccharide that is present in proteoglycans produced by interleukin 3-dependent mucosal-like mouse mast cells. Both the chondroitin ({sup 35}S)sulfate E proteoglycans and the ({sup 35}S)heparin proteoglycans were exocytosed from the ({sup 35}S)sulfate-labeled cells via perturbation of the IgE receptor, indicating that both types of {sup 35}S-labeled proteoglycans reside in the secretory granules of these human lung mast cells.

  11. Anti-allergic effects of nilotinib on mast cell-mediated anaphylaxis like reactions.

    PubMed

    El-Agamy, Dina S

    2012-04-01

    Nilotinib is a new orally bioavailable potent tyrosine kinase inhibitor that is used for the treatment of BCR-ABL-positive chronic myelogenous leukemia. However, its effect on mast cell-mediated anaphylactic reaction is still not known. The present study aimed to investigate the effect of nilotinib on the anaphylactic allergic reaction and study its possible mechanism(s) of action. Nilotinib administration prevented systemic anaphylaxis in mice, mediated by compound 48/80, in a dose- and time-dependent manner. Also, nilotinib significantly inhibited (P<0.05) allergic paw edema in rats. Furthermore, nilotinib significantly decreased (P<0.05) the IgE-mediated passive cutaneous anaphylaxis in a dose dependent manner. In addition, nilotinib dose-dependently reduced histamine release from the rat peritoneal mast cells activated either by compound 48/80 or by ovalbumin. Moreover, nilotinib attenuated the secretion of pro-inflammatory cytokine, tumor necrosis factor (TNF)-α expression in the rat peritoneal mast cells. These findings provide evidence that nilotinib inhibits mast cell-derived immediate-type allergic reactions and so it could be a candidate as an anti-allergic agent.

  12. Antibodies That Block or Activate Mouse B Cell Activating Factor of the Tumor Necrosis Factor (TNF) Family (BAFF), Respectively, Induce B Cell Depletion or B Cell Hyperplasia.

    PubMed

    Kowalczyk-Quintas, Christine; Schuepbach-Mallepell, Sonia; Vigolo, Michele; Willen, Laure; Tardivel, Aubry; Smulski, Cristian R; Zheng, Timothy S; Gommerman, Jennifer; Hess, Henry; Gottenberg, Jacques-Eric; Mackay, Fabienne; Donzé, Olivier; Schneider, Pascal

    2016-09-16

    B cell activating factor of the TNF family (BAFF), also known as B lymphocyte stimulator, is a ligand required for the generation and maintenance of B lymphocytes. In this study, the ability of different monoclonal antibodies to recognize, inhibit, or activate mouse BAFF was investigated. One of them, a mouse IgG1 named Sandy-2, prevented the binding of BAFF to all of its receptors, BAFF receptor, transmembrane activator and calcium modulating ligand interactor, and B cell maturation antigen, at a stoichiometric ratio; blocked the activity of mouse BAFF on a variety of cell-based reporter assays; and antagonized the prosurvival action of BAFF on primary mouse B cells in vitro A single administration of Sandy-2 in mice induced B cell depletion within 2 weeks, down to levels close to those observed in BAFF-deficient mice. This depletion could then be maintained with a chronic treatment. Sandy-2 and a previously described rat IgG1 antibody, 5A8, also formed a pair suitable for the sensitive detection of endogenous circulating BAFF by ELISA or using a homogenous assay. Interestingly, 5A8 and Sandy-5 displayed activities opposite to that of Sandy-2 by stimulating recombinant BAFF in vitro and endogenous BAFF in vivo These tools will prove useful for the detection and functional manipulation of endogenous mouse BAFF and provide an alternative to the widely used BAFF receptor-Fc decoy receptor for the specific depletion of BAFF in mice. PMID:27451394

  13. Aspergillus oryzae lectin induces anaphylactoid oedema and mast cell activation through its interaction with fucose of mast cell-bound non-specific IgE.

    PubMed

    Yamaki, K; Yoshino, S

    2011-11-01

    We investigated whether Aspergillus oryzae lectin (AOL), a fucose-specific lectin, induces anaphylactoid reactions and mast cell activation. The injection of AOL into footpads of mice produced a dose-related acute paw oedema. The AOL-induced oedema was attenuated by predose of histamine H1 receptor blocker or pretreatment of the lectin with fucose before injection and was not observed in SCID and mast cell-deficient WBB6F1-W/Wv mice. These results suggested that the AOL-induced anaphylactoid reaction was mediated by histamine released from mast cells. In addition, the activation of mast cells was seemed to be induced by the crosslinking of IgE on the cell surface following the binding of AOL to fucose residues in IgE. Consistent with the in vivo results, AOL induced the degranulation of the rat mast cell line RBL2H3 sensitized with monoclonal IgE. As AOL induced the increase in intracellular Ca(2+) concentration of IgE-sensitized RBL2H3 cells as well as antigen stimulation, AOL could input signals from FcεRI. The degranulation of IgE-sensitized RBL2H3 cells by AOL was diminished by pretreatment of AOL with fucose. Defucosylated IgE did not induce degranulation of RBL2H3 cells in response to AOL stimulation, in spite of its ability to induce degranulation by antigen stimulation as intact IgE. These results indicated that AOL bound to fucose residue of IgE causing antigen-independent IgE-mediated mast cell activation and anaphylactoid reactions in vitro and in vivo, respectively. AOL bound to human IgE as well as to mouse IgE, suggesting the possible implication of AOL in the allergic response to Aspergillus oryzae in humans.

  14. Mast cells drive mesenteric afferent signalling during acute intestinal ischaemia

    PubMed Central

    Jiang, Wen; Kirkup, Anthony J; Grundy, David

    2011-01-01

    Abstract Acute intestinal ischaemia stimulates visceral afferent nerves but the mechanisms responsible for this excitation are not fully understood. Mast cells may participate in this process as they are known to signal to mesenteric afferents during intestinal anaphylaxis and contribute to early inflammation and neuronal damage in response to cerebral ischaemia. We therefore hypothesised that mast cells are early responders to acute intestinal ischaemia and their activation initiates rapid signalling to the CNS via the excitation of mesenteric afferents. Primary afferent firing was recorded from a mesenteric nerve bundle supplying a segment of jejunum in anaesthetized adult rats. Acute focal ischaemia was produced by clamping the mesenteric vessels for 8 min, and reperfusion followed removal of the vessel clip. Two episodes of ischaemia–reperfusion (I–R) separated by a 30 min interval were performed. Drugs or their vehicles were administered 10 min before the 2nd I–R episode. Ischaemia caused a reproducible, intense and biphasic afferent firing that was temporally dissociated from the concomitantly triggered complex pattern of intestinal motor activity. The L-type calcium channel blocker, nifedipine, significantly attenuated this afferent firing by a mechanism independent of its action on intestinal tone. Ischaemia-induced afferent firing was also abrogated by the mast cell stabilizer, doxantrazole, and the H1 histamine receptor antagonist, pyrilamine. In contrast, the nicotinic receptor antagonist, hexamethonium, and the N-type calcium channel toxin, ω-conotoxin GVIA, each reduced the ischaemia-evoked motor inhibition but not the concurrent afferent discharge. Similarly, the cyclooxygenase inhibitor, naproxen, had no effect on the ischaemic afferent response but reduced the intestinal tone shortly from the onset of ischaemia to the early period of reperfusion. These data support a critical role for mast cell-derived histamine in the direct chemoexcitation

  15. Effect of fruits of Opuntia elatior Mill on mast cell degranulation

    PubMed Central

    Chauhan, Sanjay P.; Sheth, N. R.; Suhagia, B. N.

    2015-01-01

    Background: The presence of potentially active nutrients and their multifunctional properties make prickly pear a perfect candidate for the production of phytopharmaceutical products. Among the numerous Opuntia species, bioactive compounds have been isolated and characterized primarily from Opuntia ficus-indica, Opuntia polycantha, Opuntia stricta, Opuntia dilleni for various medicinal properties. Objective: Based on the traditional use of prickly pear for enhancement of immune function, the objective of the present study to evaluate the effect of prickly pear on mast cell degranulation function. Materials and Methods: The Opuntia fruit juice (OFJ) (10-200 μl/ml) were studied for the effect on sensitized rat peritoneal mast cell degranulation induced by immunological (egg albumin), and nonimmunological (compound 48/80) stimuli and compared with that of the reference standard, sodium cromoglycate and ketotifen (10 μg/ml). Results and Conclusion: The OFJ exhibited significantly (P < 0.001) concentration dependent inhibition of mast cell degranulation. The IC50 value of OFJ was found 12.24 and 18 μl/ml for immunological and nonimmunological induced mast cell degranulation, respectively. The betacyanin is an active principle compound in prickly pear that may responsible for mast cell stabilizing action. PMID:25883521

  16. 44. VIEW OF UMBILICAL MAST AND LAUNCH PAD FROM SOUTHWEST. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    44. VIEW OF UMBILICAL MAST AND LAUNCH PAD FROM SOUTHWEST. DOORS FOR THE UMBILICAL MAST TRENCH RAISED FOR MAINTENANCE POSITION OF 10 DEGREES. LAUNCHER IS RIGHT OF MAST; RAILS PARALLEL TO MAST. CONTROL PANELS LEFT TO RIGHT: ELECTRICAL PANEL, COMMUNICATIONS PANEL, AND MAST CONTROL PANEL. - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 East, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

  17. Mast cells, angiogenesis and cancer.

    PubMed

    Ribatti, Domenico; Crivellato, Enrico

    2011-01-01

    Mast cells (MCs) were first described by Paul Ehrlich 1 in his doctoral thesis. MCs have long been implicated in the pathogenesis of allergic reactions and certain protective responses to parasites. As most tumors contain inflammatory cell infiltrates, which often include plentiful MCs, the question as to the possible contribution of MCs to tumor development has progressively been emerging. In this chapter, the specific involvement of MCs in tumor biology and tumor fate will be considered, with particular emphasis on the capacity of these cells to stimulate tumor growth by promoting angiogenesis and lymphangiogenesis. Data from experimental carcinogenesis and from different tumor settings in human pathology will be summarized. Information to be presented will suggest that MCs may serve as a novel therapeutic target for cancer treatment. PMID:21713661

  18. In vitro studies on mast cell proliferation in N. brasiliensis infection.

    PubMed Central

    Haig, D M; Jarrett, E E; Tas, J

    1984-01-01

    We have previously shown that mast cells with the morphological and biochemical properties of mucosal mast cells (MMC) proliferate and mature in rat bone marrow cultures stimulated with factors from antigen or mitogen-activated T lymphocytes. Here we have used this system to explore the MMC hyperplasia which occurs in infections with gastrointestinal nematode parasites. Lymphocytes producing MMC-growth factor were present from day 10 onwards in N. brasiliensis-infected rats and mesenteric lymph nodes (MLN) were the major source of activated lymphocytes. When different tissues of normal rats were cultured in the presence of conditioned medium by far the greatest proliferation of MMC occurred in bone marrow, indicating an origin of MMC from haemopoietic precursors. Cultures of infected rat bone marrow yielded considerably greater numbers of MMC than cultures of normal rat bone marrow and experiments using semisolid culture media indicated that N. brasiliensis infection causes an increase in the frequency of MMC progenitors in the bone marrow. A scheme is put forward for the sequence of events occurring in vivo based on the results of these and other published experiments. The reasons for the restricted in vivo localization of MMC to the mucous membranes and associated lymph nodes is discussed. Finally we give the results of microspectrophotometric analysis which has shown that the cultured mast cell contain a non-heparin proteoglycan, thus adding a further feature to the list of MMC-like properties of these cells. PMID:6608486

  19. Benign mast cell hyperplasia and atypical mast cell infiltrates in penile lichen planus in adult men.

    PubMed

    Regauer, Sigrid; Beham-Schmid, Christine

    2014-08-01

    Introduction. Lichen planus (LP) is a chronic cytokine-mediated disease of possible auto-immune etiology. 25% of men have anogenital manifestations. Erosive penile LP causes a scarring phimosis of the foreskin in uncircumcised men. Mast cells as potent immune modulators have been implicated in a number of autoimmune and chronic inflammatory diseases, but have not been investigated in LP. Material and Methods. Formalin-fixed tissues of 117 circumcision specimens of adult men affected by LP were evaluated for the extent of mast cell and lymphocyte infiltrates, characterized immunohistochemically with antibodies to CD 3, 4, 8, 20, 21, 25, 30, 117c and human mast cell tryptase. Specimens with dense mast cell infiltrates were analyzed for point mutations of the c-kit gene (D816V). Results. Unaffected skin and modified mucosa of foreskins contained ⟨5 mast cells/mm². The inflammatory infiltrate of LP-lesions displayed ⟨15 mast cells/mm² in 33/117 foreskins, 16-40 mast cells/mm² in 22/117 and ⟩40 mast cells/mm² (average 70, range 40-100) in 62/117 foreskins. Lesional mast cells of 29/117 (24%) foreskins showed aberrant CD25-expression and/or spindled morphology, with 11/29 men having erosive LP, 13/29 a lymphocytic vasculitis and 1/28 a systemic mastocytosis. Neither CD30-expression nor c-kit mutations were identified. Atypical mast cell infiltrates in LP correlated with high disease activity, erosive LP and presence of lymphocytic vasculitis Conclusions. Increased mast cells in penile LP, mostly representing a benign hyperplasia/activation syndrome, suggests them as targets for innovative therapy options for symptomatic LP-patients not responding to corticosteroid therapy. Presently, the biological implications of atypical mast cell infiltrates in penile LP are unknown. PMID:24402730

  20. Involvement of mast cells in systemic sclerosis.

    PubMed

    Yukawa, Sonosuke; Yamaoka, Kunihiro; Sawamukai, Norifumi; Shimajiri, Shohei; Saito, Kazuyoshi; Tanaka, Yoshiya

    2010-01-01

    Systemic sclerosis is characterized by tissue fibrosis, obliterative microangiopathy and immune abnormalities. The etiology of SSc is largely unknown and is known to be resistant to existing corticosteroid and immunosuppressive drugs. Therefore, establishment of a treatment strategy especially for SSc patients with organ involvement is strongly desired. Mast cells are widely recognized as effector cells in allergic disorders and other IgE-mediated immune responses. However, recently, mast cells have become known to play a role in bridging innate immunity and adaptive immunity. Additionally, there is growing evidence of mast cell to be involved in pathogenesis of rheumatoid arthritis, and is expected as a novel therapeutic target. We describe here the role of mast cell in SSc pathology and suggest as a novel therapeutic target.

  1. Mast cell proteases as pharmacological targets.

    PubMed

    Caughey, George H

    2016-05-01

    Mast cells are rich in proteases, which are the major proteins of intracellular granules and are released with histamine and heparin by activated cells. Most of these proteases are active in the granule as well as outside of the mast cell when secreted, and can cleave targets near degranulating mast cells and in adjoining tissue compartments. Some proteases released from mast cells reach the bloodstream and may have far-reaching actions. In terms of relative amounts, the major mast cell proteases include the tryptases, chymases, cathepsin G, carboxypeptidase A3, dipeptidylpeptidase I/cathepsin C, and cathepsins L and S. Some mast cells also produce granzyme B, plasminogen activators, and matrix metalloproteinases. Tryptases and chymases are almost entirely mast cell-specific, whereas other proteases, such as cathepsins G, C, and L are expressed by a variety of inflammatory cells. Carboxypeptidase A3 expression is a property shared by basophils and mast cells. Other proteases, such as mastins, are largely basophil-specific, although human basophils are protease-deficient compared with their murine counterparts. The major classes of mast cell proteases have been targeted for development of therapeutic inhibitors. Also, a human β-tryptase has been proposed as a potential drug itself, to inactivate of snake venins. Diseases linked to mast cell proteases include allergic diseases, such as asthma, eczema, and anaphylaxis, but also include non-allergic diseases such as inflammatory bowel disease, autoimmune arthritis, atherosclerosis, aortic aneurysms, hypertension, myocardial infarction, heart failure, pulmonary hypertension and scarring diseases of lungs and other organs. In some cases, studies performed in mouse models suggest protective or homeostatic roles for specific proteases (or groups of proteases) in infections by bacteria, worms and other parasites, and even in allergic inflammation. At the same time, a clearer picture has emerged of differences in the

  2. Nonclinical evaluation of the potential for mast cell activation by an erythropoietin analog.

    PubMed

    Weaver, James L; Boyne, Michael; Pang, Eric; Chimalakonda, Krishna; Howard, Kristina E

    2015-09-15

    The erythropoietin analog peginesatide was withdrawn from marketing due to unexpected severe anaphylactic reactions associated with administration of the multi-use formulation. The adverse events occurred rapidly following the first ever administration of the drug with most affected patients becoming symptomatic in less than 30min. This is most consistent with an anaphylactoid reaction due to direct activation of mast cells. Laboratory evaluation was undertaken using rat peritoneal mast cells as the model system. Initial studies showed that high concentrations of the formulated drug as well as formulated vehicle alone could cause mast cell degranulation as measured by histamine release. The purified active drug was not able to cause histamine release whereas the vehicle filtrate and lab created drug vehicle were equally potent at causing histamine release. Individual formulations of vehicle leaving one component out showed that histamine release was due to phenol. Dose response studies with phenol showed a very sharp dose response curve that was similar in three buffer systems. Cellular analysis by flow cytometry showed that the histamine release was not due to cell death, and that changes in light scatter parameters consistent with degranulation were rapidly observed. Limited testing with primary human mast cells showed a similar dose response of histamine release with exposure to phenol. To provide in vivo confirmation, rats were injected with vehicle formulated with various concentrations of phenol via a jugular vein cannula. Significant release of histamine was detected in blood samples taken 2min after dosing at the highest concentrations tested. PMID:26079829

  3. Further studies on the effect of nitrogen dioxide on mast cells: The effect of the metabolite, nitrite

    SciTech Connect

    Fujimaki, Hidekazu ); Ozawa, Masashi ); Bissonnette, E.; Befus, A.D. )

    1993-05-01

    To evaluate the relationship between atmospheric nitrogen dioxide exposure and the development of allergic diseases, the effects of nitrite as a chemical product of inhaled nitrogen dioxide on mast cell functions were investigated. We have studied nitride-induced histamine release from two functionally distinct mast cell populations, namely peritoneal mast cells (PMC) and intestinal mucosal mast cells (IMMC) of Nippostrongylus brasiliensis-infected rats. High concentrations of nitrite alone (10, 20, and 50 mM) induced histamine release from IMMC, but not from PMC. Moreover, histamine release from PMC and IMMC stimulated with sensitizing antigen was significantly enhanced by pretreatment with 50 mM nitrite or nitrate. No differences in histamine release from nitrite-treated and control PMC were seen below 1 mM. To investigate the effect of nitrite on tumor cell cytotoxic activity, PMC were incubated with various concentrations of nitrite. Pretreatment with 5 and 50 mM nitrite markedly depressed tumor necrosis factor (TNF)-[alpha]-dependent natural cytotoxicity of PMC for the tumor target WEHI-164. Thus, high concentrations of nitrite enhanced mast cell histamine release, but depressed TNF-[alpha]-dependent cytotoxicity. However, low concentrations of nitrite (<1 mM) that would normally be produced by short-term atmospheric exposure to nitrogen dioxide may have no significant effects on mast cell functions. 27 refs., 3 figs., 1 tab.

  4. CD19xCD3 DART protein mediates human B-cell depletion in vivo in humanized BLT mice

    PubMed Central

    Tsai, Perry; Thayer, William O; Liu, Liqin; Silvestri, Guido; Nordstrom, Jeffrey L; Garcia, J Victor

    2016-01-01

    Novel therapeutic strategies are needed for the treatment of hematologic malignancies; and bispecific antibody-derived molecules, such as dual-affinity re-targeting (DART) proteins, are being developed to redirect T cells to kill target cells expressing tumor or viral antigens. Here we present our findings of specific and systemic human B-cell depletion by a CD19xCD3 DART protein in humanized BLT mice. Administration of the CD19xCD3 DART protein resulted in a dramatic sustained depletion of human CD19+ B cells from the peripheral blood, as well as a dramatic systemic reduction of human CD19+ B-cell levels in all tissues (bone marrow, spleen, liver, lung) analyzed. When human CD8+ T cells were depleted from the mice, no significant B-cell depletion was observed in response to CD19xCD3 DART protein treatment, confirming that human CD8+ T cells are the primary effector cells in this in vivo model. These studies validate the use of BLT humanized mice for the in vivo evaluation and preclinical development of bispecific molecules that redirect human T cells to selectively deplete target cells. PMID:27119115

  5. NK and NKT Cell Depletion Alters the Outcome of Experimental Pneumococcal Pneumonia: Relationship with Regulation of Interferon-γ Production.

    PubMed

    Christaki, Eirini; Diza, Evdoxia; Giamarellos-Bourboulis, Evangelos J; Papadopoulou, Nikoletta; Pistiki, Aikaterini; Droggiti, Dionysia-Irini; Georgitsi, Marianna; Machova, Alzbeta; Lambrelli, Dimitra; Malisiovas, Nicolaos; Nikolaidis, Pavlos; Opal, Steven M

    2015-01-01

    Background. Natural killer (NK) and natural killer T (NKT) cells contribute to the innate host defense but their role in bacterial sepsis remains controversial. Methods. C57BL/6 mice were infected intratracheally with 5 × 10(5) cfu of Streptococcus pneumoniae. Animals were divided into sham group (Sham); pretreated with isotype control antibody (CON) group; pretreated with anti-asialo GM1 antibody (NKd) group; and pretreated with anti-CD1d monoclonal antibody (NKTd) group before bacterial challenge. Serum and tissue samples were analyzed for bacterial load, cytokine levels, splenocyte apoptosis rates, and cell characteristics by flow cytometry. Splenocyte miRNA expression was also analyzed and survival was assessed. Results. NK cell depletion prolonged survival. Upon inhibition of NKT cell activation, spleen NK (CD3-/NK1.1+) cells increased compared to all other groups. Inhibition of NKT cell activation led to higher bacterial loads and increased levels of serum and splenocyte IFN-γ. Splenocyte miRNA analysis showed that miR-200c and miR-29a were downregulated, while miR-125a-5p was upregulated, in anti-CD1d treated animals. These changes were moderate after NK cell depletion. Conclusions. NK cells appear to contribute to mortality in pneumococcal pneumonia. Inhibition of NKT cell activation resulted in an increase in spleen NK (CD3-/NK1.1+) cells and a higher IFN-γ production, while altering splenocyte miRNA expression.

  6. Stem cell expansion during carcinogenesis in stem cell-depleted conditional telomeric repeat factor 2 null mutant mice.

    PubMed

    Bojovic, B; Ho, H-Y; Wu, J; Crowe, D L

    2013-10-24

    To examine the role of telomeric repeat-binding factor 2 (TRF2) in epithelial tumorigenesis, we characterized conditional loss of TRF2 expression in the basal layer of mouse epidermis. These mice exhibit some characteristics of dyskeratosis congenita, a human stem cell depletion syndrome caused by telomere dysfunction. The epidermis in conditional TRF2 null mice exhibited DNA damage response and apoptosis, which correlated with stem cell depletion. The stem cell population in conditional TRF2 null epidermis exhibited shorter telomeres than those in control mice. Squamous cell carcinomas induced in conditional TRF2 null mice developed with increased latency and slower growth due to reduced numbers of proliferating cells as the result of increased apoptosis. TRF2 null epidermal stem cells were found in both primary and metastatic tumors. Despite the low-grade phenotype of the conditional TRF2 null primary tumors, the number of metastatic lesions was similar to control cancers. Basal cells from TRF2 null tumors demonstrated extreme telomere shortening and dramatically increased numbers of telomeric signals by fluorescence in situ hybridization due to increased genomic instability and aneuploidy in these cancers. DNA damage response signals were detected at telomeres in TRF2 null tumor cells from these mice. The increased genomic instability in these tumors correlated with eightfold expansion of the transformed stem cell population compared with that in control cancers. We concluded that genomic instability resulting from loss of TRF2 expression provides biological advantages to the cancer stem cell population.

  7. A Microplate Assay to Assess Chemical Effects on RBL-2H3 Mast Cell Degranulation: Effects of Triclosan without Use of an Organic Solvent

    PubMed Central

    Shim, Juyoung; Gosse, Julie A.

    2013-01-01

    Mast cells play important roles in allergic disease and immune defense against parasites. Once activated (e.g. by an allergen), they degranulate, a process that results in the exocytosis of allergic mediators. Modulation of mast cell degranulation by drugs and toxicants may have positive or adverse effects on human health. Mast cell function has been dissected in detail with the use of rat basophilic leukemia mast cells (RBL-2H3), a widely accepted model of human mucosal mast cells3-5. Mast cell granule component and the allergic mediator β-hexosaminidase, which is released linearly in tandem with histamine from mast cells6, can easily and reliably be measured through reaction with a fluorogenic substrate, yielding measurable fluorescence intensity in a microplate assay that is amenable to high-throughput studies1. Originally published by Naal et al.1, we have adapted this degranulation assay for the screening of drugs and toxicants and demonstrate its use here. Triclosan is a broad-spectrum antibacterial agent that is present in many consumer products and has been found to be a therapeutic aid in human allergic skin disease7-11, although the mechanism for this effect is unknown. Here we demonstrate an assay for the effect of triclosan on mast cell degranulation. We recently showed that triclosan strongly affects mast cell function2. In an effort to avoid use of an organic solvent, triclosan is dissolved directly into aqueous buffer with heat and stirring, and resultant concentration is confirmed using UV-Vis spectrophotometry (using ε280 = 4,200 L/M/cm)12. This protocol has the potential to be used with a variety of chemicals to determine their effects on mast cell degranulation, and more broadly, their allergic potential. PMID:24300285

  8. Immunomodulation of mast cells by nutrients.

    PubMed

    Hagenlocher, Yvonne; Lorentz, Axel

    2015-01-01

    In the past decades an increasing prevalence of allergic disorders was observed in industrialized countries. Thus, it is necessary to develop adequate therapeutic and preventive strategies. Many of the conservative strategies possess diverse harmful side effects. Therefore agents with fewer side effects and a better compliance among afflicted patients would be of interest. Especially substances with natural origin acting immunomodulatory on mast cells - the key effector cells of allergic diseases - could be used. Among them there are components of the daily diet such as distinct fatty acids and amino acids as well as a range of secondary plant substances such as carotenoids, flavonoids and spices. These nutritional substances could be applied as nutraceuticals in the therapy of mast cell associated diseases. Many of these substances show inhibitory influences on the release of prestored mast cell mediators such as histamine or de novo expression of mast cell mediators such as cytokines and eicosanoids which are involved in the pathogenesis of mast cell associated inflammatory conditions like allergic reactions.

  9. Vaccine adjuvants: Tailor-made mast-cell granules

    NASA Astrophysics Data System (ADS)

    Gunzer, Matthias

    2012-03-01

    Mast cells induce protective immune responses through secretion of stimulatory granules. Microparticles modelled after mast-cell granules are now shown to replicate and enhance the functions of their natural counterparts and to direct the character of the resulting immunity.

  10. A novel, blocking, Fc-silent anti-CD40 monoclonal antibody prolongs nonhuman primate renal allograft survival in the absence of B cell depletion.

    PubMed

    Cordoba, F; Wieczorek, G; Audet, M; Roth, L; Schneider, M A; Kunkler, A; Stuber, N; Erard, M; Ceci, M; Baumgartner, R; Apolloni, R; Cattini, A; Robert, G; Ristig, D; Munz, J; Haeberli, L; Grau, R; Sickert, D; Heusser, C; Espie, P; Bruns, C; Patel, D; Rush, J S

    2015-11-01

    CD40-CD154 pathway blockade prolongs renal allograft survival in nonhuman primates (NHPs). However, antibodies targeting CD154 were associated with an increased incidence of thromboembolic complications. Antibodies targeting CD40 prolong renal allograft survival in NHPs without thromboembolic events but with accompanying B cell depletion, raising the question of the relative contribution of B cell depletion to the efficacy of anti-CD40 blockade. Here, we investigated whether fully silencing Fc effector functions of an anti-CD40 antibody can still promote graft survival. The parent anti-CD40 monoclonal antibody HCD122 prolonged allograft survival in MHC-mismatched cynomolgus monkey renal allograft transplantation (52, 22, and 24 days) with accompanying B cell depletion. Fc-silencing yielded CFZ533, an antibody incapable of B cell depletion but still able to potently inhibit CD40 pathway activation. CFZ533 prolonged allograft survival and function up to a defined protocol endpoint of 98-100 days (100, 100, 100, 98, and 76 days) in the absence of B cell depletion and preservation of good histological graft morphology. CFZ533 was well-tolerated, with no evidence of thromboembolic events or CD40 pathway activation and suppressed a gene signature associated with acute rejection. Thus, use of the Fc-silent anti-CD40 antibody CFZ533 appears to be an attractive approach for preventing solid organ transplant rejection.

  11. Lung mast cells in plexogenic pulmonary arteriopathy.

    PubMed Central

    Heath, D; Yacoub, M

    1991-01-01

    The numbers of mast cells/mm2 of lung parenchyma were counted in four controls, 15 cases of primary plexogenic pulmonary arteriopathy (PPA), and 17 cases in which the arteriopathy was secondary to congenital heart disease, to determine if increased numbers occur in PPA and with what stage of disease they might be associated. Considerable accumulations of lung mast cells may occur in this disease, but these are not closely related to any particular histological stage in the development of the arteriopathy. It is postulated that while mast cells could conceivably exert a vasodilatory effect on constricted small pulmonary arteries, it seems more likely that they are part of the parenchymal changes that commonly develop in this disease. Images PMID:1791199

  12. Mast Cell-Mediated Mechanisms of Nociception

    PubMed Central

    Aich, Anupam; Afrin, Lawrence B.; Gupta, Kalpna

    2015-01-01

    Mast cells are tissue-resident immune cells that release immuno-modulators, chemo-attractants, vasoactive compounds, neuropeptides and growth factors in response to allergens and pathogens constituting a first line of host defense. The neuroimmune interface of immune cells modulating synaptic responses has been of increasing interest, and mast cells have been proposed as key players in orchestrating inflammation-associated pain pathobiology due to their proximity to both vasculature and nerve fibers. Molecular underpinnings of mast cell-mediated pain can be disease-specific. Understanding such mechanisms is critical for developing disease-specific targeted therapeutics to improve analgesic outcomes. We review molecular mechanisms that may contribute to nociception in a disease-specific manner. PMID:26690128

  13. Perivascular mast cells regulate vein graft neointimal formation and remodeling

    PubMed Central

    Grassia, Gianluca; Cambrook, Helen; Ialenti, Armando; MacRitchie, Neil; Carberry, Jaclyn; Lawrence, Catherine

    2015-01-01

    Objective. Emerging evidence suggests an important role for mast cells in vein graft failure. This study addressed the hypothesis that perivascular mast cells regulate in situ vascular inflammatory and proliferative responses and subsequent vein graft neointimal lesion formation, using an optimized local mast cell reconstitution method. Methods and Results. Neointimal hyperplasia was induced by insertion of a vein graft into the right carotid artery in wild type and mast cell deficient KitW−sh/W−sh mice. In some experiments, mast cells were reconstituted systemically (tail vein injection of bone marrow-derived mast cells) or locally (directly into the right neck area) prior to vein grafting. Vein graft neointimal lesion formation was significantly (P < 0.05) reduced in KitW−sh/W−sh mice. Mast cell deficiency reduced the number of proliferating cells, and inhibited L-selectin, CCL2, M-CSF and MIP-3α expression in the vein grafts. Local but not systemic mast cell reconstitution restored a perivascular mast cell population that subsequently promoted neointimal formation in mast cell deficient mice. Conclusion. Our data demonstrate that perivascular mast cells play a key role in promoting neointima formation by inducing local acute inflammatory and proliferative responses. These results suggest that ex vivo intraoperative targeting of mast cells may have therapeutic potential for the prevention of pathological vein graft remodeling. PMID:26312183

  14. 53. VIEW FROM FLOOR OF MAST TRENCH SHOWING BASE OF ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    53. VIEW FROM FLOOR OF MAST TRENCH SHOWING BASE OF ERECT UMBILICAL MAST. AIR-CONDITIONING DUCTS VISIBLE ON RIGHT SIDE OF MAST. HYDRAULIC ACTUATOR ARMS FOR OPENING TRENCH DOORS VISIBLE ON LEFT SIDE OF PHOTO. 'DOOR STOP' PEDESTAL IN FOREGROUND. - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 West, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

  15. 43. TOP PART OF UMBILICAL MAST, NORTH AND WEST SIDES. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    43. TOP PART OF UMBILICAL MAST, NORTH AND WEST SIDES. AIR CONDITIONING DUCTING IS VISIBLE ON INTERIOR OF MAST. RAIL IS VISIBLE LEFT OF THE MAST. - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 East, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

  16. The Michigan Alcoholism Screening Test (MAST): A Statistical Validation Analysis

    ERIC Educational Resources Information Center

    Laux, John M.; Newman, Isadore; Brown, Russ

    2004-01-01

    This study extends the Michigan Alcoholism Screening Test (MAST; M. L. Selzer, 1971) literature base by examining 4 issues related to the validity of the MAST scores. Specifically, the authors examine the validity of the MAST scores in light of the presence of impression management, participant demographic variables, and item endorsement…

  17. Rho guanine nucleotide dissociation inhibitor protein (RhoGDI) inhibits exocytosis in mast cells.

    PubMed Central

    Mariot, P; O'Sullivan, A J; Brown, A M; Tatham, P E

    1996-01-01

    Introducing non-hydrolysable analogues of GTP into the cytosolic compartment of mast cells results in exocytotic secretion through the activation of GTP binding proteins. The identity and mechanism of action of these proteins are not established. We have investigated the effects of Rho GDP dissociation inhibitor (RhoGDI) on exocytosis induced by guanosine 5'-O-(3-thiotriphosphate) (GTP-gamma-S) in rat mast cells, introducing the protein into cells by means of a patch pipette and recording the progress of exocytosis by monitoring cell capacitance. To allow time for the protein to enter the cells and find its correct location, stimulation was provided 5-10 min after patch rupture by photolysing caged GTP-gamma-S included in the pipette solution. When bovine RhoGDI was introduced into mast cells, exocytosis was inhibited at concentrations of 200-400 nM for native protein and 800 nM to 8 microM for the recombinant form. Protein denatured by heat or N-ethylmaleimide treatment did not inhibit. In permeabilized cells, recombinant RhoGDI increased the rate at which cells lose their ability to respond to GTP-gamma-S. These data demonstrate that one or more small GTP binding proteins of the Rho family has a central role in the exocytotic mechanism in mast cells. Images PMID:8978674

  18. Inhibitory effects of mast cell-mediated allergic reactions by cell cultured Siberian Ginseng.

    PubMed

    Jeong, H J; Koo, H N; Myung, N I; Shin, M K; Kim, J W; Kim, D K; Kim, K S; Kim, H M; Lee, Y M

    2001-02-01

    The crude drug "Siberian Ginseng (SG)" has long been used in empirical Oriental medicine for the nonspecific enhancement of resistance in humans and animals. In this study, we investigated the effect of cell cultured SG by oral administration in mast cell-mediated allergic reactions. SG dose-dependently inhibited compound 48/80-induced systemic allergy with doses of 10(-2) to 1 g/kg 1 h before oral administration. Of special note, SG inhibited systemic allergy with the dose of 1 g/kg by 25%. SG (1 g/kg) also inhibited passive cutaneous allergic reaction by 51%. SG dose-dependently inhibited histamine release from rat peritoneal mast cells. When SG (0.01 mg/ml) was added, the secretion of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 in antidinitrophenyl (DNP) IgE antibody-stimulated mast cells was inhibited 39.5% and 23.3%, respectively. In addition, SG inhibited anti-DNP IgE antibody-stimulated TNF-alpha protein expression in mast cells. Our studies provide evidence that SG may be beneficial in the treatment of various types of allergic diseases.

  19. Extendable retractable telescopic mast for deployable structures

    NASA Technical Reports Server (NTRS)

    Schmid, M.; Aguirre, M.

    1986-01-01

    The Extendable and Retractable Mast (ERM) which is presently developed by Dornier in the frame of an ESA-contract, will be used to deploy and retract large foldable structures. The design is based on a telescopic carbon-fiber structure with high stiffness, strength and pointing accuracy. To verify the chosen design, a breadboard model of an ERM was built and tested under thermal vacuum (TV)-conditions. It is planned as a follow-on development to manufacture and test an Engineering Model Mast. The Engineering Model will be used to establish the basis for an ERM-family covering a wide range of requirements.

  20. Recovery from T cell depletion during murine listeriosis and effect on a T-dependent antibody response.

    PubMed Central

    Chan, Y Y; Cheers, C

    1982-01-01

    During the infection of mice with Listeria monocytogenes, there is a profound depletion of T (Thy-1+ Ig-) lymphocytes between days 1 and 4, followed by an increase in T cells to three times normal levels by day 9. The recovery of T cell numbers required cell proliferation, being sensitive to vinblastin and cyclophosphamide. Adult thymectomy 6 months before infection had no effect on recovery. The repopulating cells were no more sensitive than normal T cells to hydrocortisone. B lymphocytes (Ig+ cells) and null (Thy-1-Ig-) cells increased from day 1 after the injection of either live or (in contrast to T cells) killed Listeria organisms. Their increase was inhibited by vinblastin and cyclophosphamide. Despite T cell depletion, no depression of the antibody response to the T-dependent antigen, sheep erythrocytes, occurred during infection or when spleen cells were adoptively transferred from infected mice to irradiated recipients. PMID:6982870

  1. Recent advances in haploidentical hematopoietic stem cell transplantation using ex vivo T cell-depleted graft in children and adolescents

    PubMed Central

    Koh, Kyung-Nam; Seo, Jong Jin

    2016-01-01

    Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment for children and adolescents with various malignant and non-malignant diseases. While human leukocyte antigen (HLA)-identical sibling donor is the preferred choice, matched unrelated volunteer donor is another realistic option for successful HSCT. Unfortunately, it is not always possible to find a HLA-matched donor for patients requiring HSCT, leading to a considerable number of deaths of patients without undergoing transplantation. Alternatively, allogeneic HSCT from haploidentical family members could provide donors for virtually all patients who need HSCT. Although the early attempts at allogeneic HSCT from haploidentical family donor (HFD) were disappointing, recent advances in the effective ex vivo depletion of T cells or unmanipulated in vivo regulation of T cells, better supportive care, and optimal conditioning regimens have significantly improved the outcomes of haploidentical HSCT. The ex vivo techniques used to remove T cells have evolved from the selection of CD34+ hematopoietic stem cell progenitors to the depletion of CD3+ cells, and more recently to the depletion of αβ+ T cells. The recent emerging evidence for ex vivo T cell-depleted haploidentical HSCT has provided additional therapeutic options for pediatric patients with diseases curable by HSCT but has not found a suitable related or unrelated donor. This review discusses recent advances in haploidentical HSCT, focusing on transplant using ex vivo T cell-depleted grafts. In addition, our experiences with this novel approach for the treatment of pediatric patients with malignant and non-malignant diseases are described. PMID:27104186

  2. Ex Vivo T Cell Depleted versus Unmodified Allografts in Patients with Acute Myeloid Leukemia in First Complete Remission

    PubMed Central

    Bayraktar, Ulas D.; de Lima, Marcos; Saliba, Rima M.; Maloy, Molly; Castro-Malaspina, Hugo R.; Chen, Julianne; Rondon, Gabriela; Chiattone, Alexander; Jakubowski, Ann A.; Boulad, Farid; Kernan, Nancy A.; O'Reilly, Richard J.; Champlin, Richard E.; Giralt, Sergio; Andersson, Borje S.; Papadopoulos, Esperanza B.

    2014-01-01

    Purpose To retrospectively compare the clinical outcomes after transplantation of T cell depleted (TCD) and unmodified allografts in patients with acute myeloid leukemia (AML) in first complete remission (CR1). Patients and methods Patients received TCD grafts at Memorial Sloan-Kettering Cancer Center (MSKCC, N=115) between 2001 and 2010 using the following preparative regimens: Hyperfractionated total body irradiation (HFTBI) /thiotepa /fludarabine; HFTBI /thiotepa /cyclophosphamide; i.v. busulfan/melphalan/fludarabine. T cell depletion was performed by one of two immunomagnetic CD34+ cell selection methods for peripheral blood grafts or by soybean lectin agglutination followed by sRBC-rosette depletion for bone marrow grafts. No additional graft-versus-host disease (GVHD) prophylaxis was administered. Patients received unmodified grafts at MD Anderson Cancer Center (MDACC, N=181) after conditioning with busulfan /fludarabine and GVHD prophylaxis with tacrolimus /mini-methotrexate. Patients with unrelated or HLA-mismatched donors received anti-thymocyte globulin (ATG) at both centers with some recipients of matched related donor TCD transplants also receiving ATG depending upon the preparative regimen. Results TCD graft recipients were more likely to be older, receive a mismatched transplant, and have peripheral blood used as the graft source. The incidences of grade 2-4 acute GVHD and chronic GVHD were significantly lower in the TCD graft group (5% vs. 18% and 13% vs. 53%). Three-year relapse-free (RFS) and overall survival (OS) rates were 58% and 57% in recipients of TCD grafts, and 60% and 66% in recipients of unmodified grafts (P=NS). Conclusion Survival and RFS are similar after TCD and conventional transplants from related/unrelated donors in patients with AML in CR1 but TCD significantly reduces GVHD. PMID:23467126

  3. Recent advances in haploidentical hematopoietic stem cell transplantation using ex vivo T cell-depleted graft in children and adolescents.

    PubMed

    Im, Ho Joon; Koh, Kyung-Nam; Seo, Jong Jin

    2016-03-01

    Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment for children and adolescents with various malignant and non-malignant diseases. While human leukocyte antigen (HLA)-identical sibling donor is the preferred choice, matched unrelated volunteer donor is another realistic option for successful HSCT. Unfortunately, it is not always possible to find a HLA-matched donor for patients requiring HSCT, leading to a considerable number of deaths of patients without undergoing transplantation. Alternatively, allogeneic HSCT from haploidentical family members could provide donors for virtually all patients who need HSCT. Although the early attempts at allogeneic HSCT from haploidentical family donor (HFD) were disappointing, recent advances in the effective ex vivo depletion of T cells or unmanipulated in vivo regulation of T cells, better supportive care, and optimal conditioning regimens have significantly improved the outcomes of haploidentical HSCT. The ex vivo techniques used to remove T cells have evolved from the selection of CD34(+) hematopoietic stem cell progenitors to the depletion of CD3(+) cells, and more recently to the depletion of αβ(+) T cells. The recent emerging evidence for ex vivo T cell-depleted haploidentical HSCT has provided additional therapeutic options for pediatric patients with diseases curable by HSCT but has not found a suitable related or unrelated donor. This review discusses recent advances in haploidentical HSCT, focusing on transplant using ex vivo T cell-depleted grafts. In addition, our experiences with this novel approach for the treatment of pediatric patients with malignant and non-malignant diseases are described.

  4. p161, a murine membrane protein expressed on mast cells and some macrophages, is mouse CD13/aminopeptidase N.

    PubMed

    Chen, H; Kinzer, C A; Paul, W E

    1996-09-15

    pl6l is a membrane glycoprotein expressed on mast cells and on activated macrophages but on few if any other cells of hematopoietic lineages. Its lack of expression on basophils makes it useful to distinguish mast cells from basophils and aids in the analysis of mast cells and their precursors. p161 was purified from the mast cell line CFTL-12 by affinity chromatography and subjected to limited proteolysis. The sequences of the resultant peptides indicated that p161 is homologous with rat and human CD13/aminopeptidase N. Using oligonucleotide primers derived from rat CD13 cDNA, a mouse cDNA was obtained. Its deduced amino acid sequence displays 87% identity with rat CD13 and 76 % identity with human CD13. Expression of the mouse cDNA in M12 cells, which are p161 negative, renders these cells positive for staining with the monoclonal anti-p161 Ab, K-1. Furthermore, a mAb raised against partially purified mouse intestinal aminopeptidase N specifically blocked the binding of K-1 to both CFTL-12 cells and the transfected M12 cells. These results strongly indicate that mouse p161 is CD13/aminopeptidase N. Northern blot analysis shows that p161 mRNA is most abundantly expressed in the intestinal tract and kidney and is present in liver, lymph node, spleen, and brain.

  5. GPR30 decreases cardiac chymase/angiotensin II by inhibiting local mast cell number

    SciTech Connect

    Zhao, Zhuo; Wang, Hao; Lin, Marina; Groban, Leanne

    2015-03-27

    Chronic activation of the novel estrogen receptor GPR30 by its agonist G1 mitigates the adverse effects of estrogen (E2) loss on cardiac structure and function. Using the ovariectomized (OVX) mRen2.Lewis rat, an E2-sensitive model of diastolic dysfunction, we found that E2 status is inversely correlated with local cardiac angiotensin II (Ang II) levels, likely via Ang I/chymase-mediated production. Since chymase is released from cardiac mast cells during stress (e.g., volume/pressure overload, inflammation), we hypothesized that GPR30-related cardioprotection after E2 loss might occur through its opposing actions on cardiac mast cell proliferation and chymase production. Using real-time quantitative PCR, immunohistochemistry, and immunoblot analysis, we found mast cell number, chymase expression, and cardiac Ang II levels were significantly increased in the hearts of OVX-compared to ovary-intact mRen2.Lewis rats and the GPR30 agonist G1 (50 mg/kg/day, s.c.) administered for 2 weeks limited the adverse effects of estrogen loss. In vitro studies revealed that GPR30 receptors are expressed in the RBL-2H3 mast cell line and G1 inhibits serum-induced cell proliferation in a dose-dependent manner, as determined by cell counting, BrdU incorporation assay, and Ki-67 staining. Using specific antagonists to estrogen receptors, blockage of GPR30, but not ERα or ERβ, attenuated the inhibitory effects of estrogen on BrdU incorporation in RBL-2H3 cells. Further study of the mechanism underlying the effect on cell proliferation showed that G1 inhibits cyclin-dependent kinase 1 (CDK1) mRNA and protein expression in RBL-2H3 cells in a dose-dependent manner. - Highlights: • GPR30 activation limits mast cell number in hearts from OVX mRen2.Lewis rats. • GPR30 activation decreases cardiac chymase/angiotensin II after estrogen loss. • GPR30 activation inhibits RBL-2H3 mast cell proliferation and CDK1 expression.

  6. Mast Cell: A Multi-Functional Master Cell

    PubMed Central

    Krystel-Whittemore, Melissa; Dileepan, Kottarappat N.; Wood, John G.

    2016-01-01

    Mast cells are immune cells of the myeloid lineage and are present in connective tissues throughout the body. The activation and degranulation of mast cells significantly modulates many aspects of physiological and pathological conditions in various settings. With respect to normal physiological functions, mast cells are known to regulate vasodilation, vascular homeostasis, innate and adaptive immune responses, angiogenesis, and venom detoxification. On the other hand, mast cells have also been implicated in the pathophysiology of many diseases, including allergy, asthma, anaphylaxis, gastrointestinal disorders, many types of malignancies, and cardiovascular diseases. This review summarizes the current understanding of the role of mast cells in many pathophysiological conditions. PMID:26779180

  7. Inhibitory effect of açaí (Euterpe oleracea Mart.) pulp on IgE-mediated mast cell activation.

    PubMed

    Horiguchi, Tomoko; Ishiguro, Nahoko; Chihara, Kazuyasu; Ogi, Kazuhiro; Nakashima, Kenji; Sada, Kiyonao; Hori-Tamura, Naoko

    2011-05-25

    The palm fruit açaí is known to have potential health benefits due to its antioxidant scavenging capacities. Pretreatment of IgE-sensitized mouse primary cultured mast cells with açaí pulp resulted in the dramatic suppression of antigen-induced degranulation in a dose-dependent manner. Similarly, açaí suppressed IgE-mediated degranulation and transcription of the cytokine genes from a cultured mast cell line of rat basophilic leukemia (RBL)-2H3 cells. Açaí could selectively inhibit FcεRI signaling pathways. Furthermore, the FcεRI-mediated complementary signaling pathway was also suppressed by açaí. These results demonstrate that açaí is a potent inhibitor of IgE-mediated mast cell activation.

  8. A protective role of mast cells in intestinal tumorigenesis.

    PubMed

    Sinnamon, Mark J; Carter, Kathy J; Sims, Lauren P; Lafleur, Bonnie; Fingleton, Barbara; Matrisian, Lynn M

    2008-04-01

    Mast cells have been observed in numerous types of tumors; however, their role in carcinogenesis remains poorly understood. The majority of epidemiological evidence suggests a negative association between the presence of mast cells and tumor progression in breast, lung and colonic neoplasms. Intestinal adenomas in the multiple intestinal neoplasia (Min, APC(Min/+)) mouse displayed increased numbers of mast cells and increased abundance of mast cell-associated proteinases as determined by transcriptional profiling with the Hu/Mu ProtIn microarray. To examine the role of mast cells in intestinal tumorigenesis, a mutant mouse line deficient in mast cells, Sash mice (c-kit(W-sh/W-sh)), was crossed with the Min mouse, a genetic model of intestinal neoplasia. The resulting mast cell-deficient Min-Sash mice developed 50% more adenomas than littermate controls and the tumors were 33% larger in Min-Sash mice. Mast cell deficiency did not affect tumor cell proliferation; however, apoptosis was significantly inhibited in mast cell-deficient mice. Mast cells have been shown to act as critical upstream regulators of numerous inflammatory cells. Neutrophil, macrophage and T cell populations were similar between Min and Min-Sash mice; however, eosinophils were significantly less abundant in tumors obtained from Min-Sash animals. These results indicate a protective, antitumor role of mast cells in a genetic model of early-stage intestinal tumorigenesis. PMID:18258601

  9. [Anthocyanidin inhibits immunoglobulin E-mediated allergic response in mast cells].

    PubMed

    Jin, Guang-Ri; Hong, Hai; Jin, Guang-Yu; Li, Ying-Zhe; Li, Guang-Zhao; Yan, Guang-Hai

    2012-01-01

    This study is to investigate the anti-allergic effect of anthocyanidin and to explore its possible mechanism. The experiments of passive cutaneous anaphylaxis reaction (PCA) and colorimetry were used to determine the effect of anthocyanidin on degranulation of mast cells in vivo. For in vitro study, various concentrations of anthocyanidin (100, 50 and 25 micromol x L(-1)) were added to the culture medium of mast cells cultured with 100 microg x L(-1) of dinitrophenyl (DNP) specific IgE overnight. The azelastine (100 micromol x L(-1)) was selected as the positive control. The antigen (DNP-human serum albumin, DNP-HAS)-induced release of degranulation was measured by enzymatic assay, histamine was determined by EIA, and interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were measured by Western blotting, separately. In addition, the effects of anthocyanidin on phosphorylation of NF-kappaB, p38MAPK and Akt were observed by Western blotting. The results showed that treatments with anthocyanidin (100 and 50 mg x kg(-1)) were followed by a decrease in PCA of rats. Anthocyanidin (100 and 50 micromol x L(-1)) obviously suppressed the degranulation from mast cells, whereas results from anthocyanidin (100 and 50 micromol x L(-1)) group indicated significant inhibitory effect on histamine, the calcium uptake, TNF-alpha, IL-6, phosphorylation of NF-kappaB, p38MAPK and Akt of mast cells induced by antigen. Anthocyanidin may suppress the anaphylactic reaction by inhibiting the action of mast cells. NF-kappaB, p38MAPK and Akt at least in part contribute to this event. PMID:22493802

  10. Spatial distribution of mast cells in chronic venous leg ulcers.

    PubMed

    Abd-El-Aleem, S A; Morgan, C; Ferguson, M W J; McCollum, C N; Ireland, G W

    2005-01-01

    Chronic venous leg ulcers (CVUs) show chronic inflammation but different pathological changes occur in different parts of the ulcer. There is a lack of re-epithelialisation and defective matrix deposition in the ulcer base but epidermal hyperproliferation and increased matrix deposition in the surrounding skin. The role of mast cells in wound healing, inflammation, fibrosis and epidermal hyperproliferation has been extensively studied but less is known about their role in CVUs. In the present study, we investigated the distribution of mast cells in CVUs with specific consideration of the differences between the ulcer base and the skin surrounding the ulcer. Both histochemical and immunohistological methods were used to detect the mast cell marker tryptase in frozen sections of CVU biopsies. Mast cells were counted in the dermis of normal skin, in the ulcer base and in the skin surrounding the ulcer. Double immunofluorescence staining was used to study the location of mast cells in relation to blood vessels. In normal skin few mast cells were seen in the dermis but none in the epidermis. However in CVUs there was a significant increase in intact and degranulated mast cells in the surrounding skin and ulcer edge (184 per field, p<0.003) of CVUs and a significant reduction in the ulcer base (20.5 per field p<0.05) in comparison to normal skin (61 per field). In CVUs mast cells showed a characteristic location near the epithelial basement membrane whilst mast cell granules and phantom cells (mast cells devoid of granules) were predominantly seen in the epidermis. In the dermis, mast cells were seen associated with blood vessels. The marked increase in mast cells in the surrounding skin of CVUs and depletion of mast cells in the ulcer base could implicate mast cell mediators in the pathological changes in CVUs particularly in the epidermal and vascular changes occurring in the surrounding skin.

  11. Mosla dianthera inhibits mast cell-mediated allergic reactions through the inhibition of histamine release and inflammatory cytokine production

    SciTech Connect

    Lee, Dong-Hee; Kim, Sang-Hyun . E-mail: shkim72@knu.ac.kr; Eun, Jae-Soon; Shin, Tae-Yong . E-mail: tyshin@woosuk.ac.kr

    2006-11-01

    In this study, we investigated the effect of the aqueous extract of Mosla dianthera (Maxim.) (AEMD) on the mast cell-mediated allergy model and studied the possible mechanism of action. Mast cell-mediated allergic disease is involved in many diseases such as asthma, sinusitis and rheumatoid arthritis. The discovery of drugs for the treatment of allergic disease is an important subject in human health. AEMD inhibited compound 48/80-induced systemic reactions in mice. AEMD decreased immunoglobulin E-mediated local allergic reactions, passive cutaneous anaphylaxis. AEMD attenuated intracellular calcium level and release of histamine from rat peritoneal mast cells activated by compound 48/80. Furthermore, AEMD attenuated the phorbol 12-myristate 13-acetate (PMA) and calcium ionophore A23187-stimulated TNF-{alpha}, IL-8 and IL-6 secretion in human mast cells. The inhibitory effect of AEMD on the pro-inflammatory cytokines was nuclear factor-{kappa}B (NF-{kappa}B) dependent. AEMD decreased PMA and A23187-induced degradation of I{kappa}B{alpha} and nuclear translocation of NF-{kappa}B. Our findings provide evidence that AEMD inhibits mast cell-derived immediate-type allergic reactions and involvement of pro-inflammatory cytokines and NF-{kappa}B in these effects.

  12. Stress-induced dura vascular permeability does not develop in mast cell-deficient and neurokinin-1 receptor knockout mice.

    PubMed

    Kandere-Grzybowska, Kristiana; Gheorghe, Daniela; Priller, Josef; Esposito, Pamela; Huang, Man; Gerard, Norma; Theoharides, Theoharis C

    2003-08-01

    Migraine headaches are often precipitated by stress and seem to involve neurogenic inflammation (NI) of the dura mater associated with the sensation of throbbing pain. Trigeminal nerve stimulation had been reported to activate rat dura mast cells and increase vascular permeability, effects inhibited by neonatal pretreatment with capsaicin implicating sensory neuropeptides, such as substance P (SP). The aim of the present study was to investigate NI, assessed by extravasation of 99-Technetium-gluceptate (99Tc-G), as well as the role of mast cells, SP and its receptor (NK-1R) in dura mater of mice in response to acute stress. Restraint stress for thirty min significantly increased 99Tc-G extravasation in the dura mater of C57BL mice. This effect was absent in W/W(v) mast cell-deficient mice and NK-1 receptor knockout mice (NK-1R-/-), but was unaltered in SP knockout mice (SP-/-). Acute restraint stress also resulted in increased dura mast cell activation in C57BL mice, but not in NK-1R-/- mice. These data demonstrate for the first time that acute stress triggers NI and mast cell activation in mouse dura mater through the activation of NK-1 receptors. The fact that SP-/- mice had intact vascular permeability response to stress indicates that some other NK-1 receptor agonist may substitute for SP. These results may help explain initial events in pathogenesis of stress-induced migraines.

  13. Blockade of mast cell histamine secretion in response to neurotensin by SR 48692, a nonpeptide antagonist of the neurotensin brain receptor.

    PubMed Central

    Miller, L A; Cochrane, D E; Carraway, R E; Feldberg, R S

    1995-01-01

    1. Pretreatment of rat isolated mast cells with SR 48692, a nonpeptide antagonist of the neurotensin (NT) receptor, prevented histamine secretion in response to NT. 2. This inhibition was rapid in onset (approximately 1 min) and dependent upon the concentration of SR 48692 (IC50 approximately 1-10 nM). 3. SR 48692 (1-1000 nM) did not inhibit histamine secretion elicited by substance P, bradykinin or compound 48/80, or by anti-IgE stimulation of sensitized mast cells. 4. When SR 48692 was injected intradermally (5 pmol in 50 microliters) into anaesthetized rats, 15 min before the intradermal injection of NT, it reduced the effect of NT on vascular permeability. 5. When injected intravenously, SR 48692 attenuated the effects of NT on haematocrit and blood stasis. 6. These results demonstrate that SR 48692 selectively antagonizes the actions of NT on rat isolated mast cells as well as mast cells in vivo. Given the demonstrated specific interaction of SR 48692 with receptors for NT in brain, our results suggest the presence of specific NT receptors on mast cells. PMID:7541694

  14. Mast Cells Produce a Unique Chondroitin Sulfate Epitope.

    PubMed

    Farrugia, Brooke L; Whitelock, John M; O'Grady, Robert; Caterson, Bruce; Lord, Megan S

    2016-02-01

    The granules of mast cells contain a myriad of mediators that are stored and protected by the sulfated glycosaminoglycan (GAG) chains that decorate proteoglycans. Whereas heparin is the GAG predominantly associated with mast cells, mast cell proteoglycans are also decorated with heparan sulfate and chondroitin sulfate (CS). This study investigated a unique CS structure produced by mast cells that was detected with the antibody clone 2B6 in the absence of chondroitinase ABC digestion. Mast cells in rodent tissue sections were characterized using toluidine blue, Leder stain and the presence of mast cell tryptase. The novel CS epitope was identified in rodent tissue sections and localized to cells that were morphologically similar to cells chemically identified as mast cells. The rodent mast cell-like line RBL-2H3 was also shown to express the novel CS epitope. This epitope co-localized with multiple CS proteoglycans in both rodent tissue and RBL-2H3 cultured cells. These findings suggest that the novel CS epitope that decorates mast cell proteoglycans may play a role in the way these chains are structured in mast cells.

  15. Inhibition of mast cell secretion by oxidation products of natural polyamines.

    PubMed

    Vliagoftis, H; Boucher, W S; Mak, L L; Theoharides, T C

    1992-05-28

    Mast cells secrete many biologically active compounds upon stimulation by immunoglobulin E (IgE) and specific antigen (Ag), anaphylatoxins, as well as a number of cationic compounds which include drugs, kinins and neuropeptides. The effects of the two naturally occurring polyamines, spermine (SP) and spermidine (SPD), on mast cell secretion were studied because they have been implicated in the modulation of cellular processes, possibly through their cationic charge or the regulation of calcium ions. SP and SPD over the range of 10(-7) to 10(-4) M inhibited the release of 5-hydroxytryptamine (5-HT, serotonin) triggered by compound 48/80 (C48/80) in a time- and concentration-dependent manner, as long as at least 2% calf serum (CS) was present. SP also inhibited secretion of both histamine and serotonin stimulated immunologically by using IgE and anti-rat IgE. This inhibition was not accompanied by cytotoxicity. The major available polyamine metabolites tested, N1-acetyl spermine (N1-acSP) and N8-acetyl spermidine (N8-acSPD), also showed inhibition in the presence of CS, whereas putrescine, N8,N1-hexamethylene-bis-acetamide (HMBA) and benzylamine did not. Fetal bovine serum (FBS), as well as human and rat serum, which do not contain polyamine oxidase, did not result in any inhibition with the polyamines tested. Inhibitors of the polyamine oxidase blocked the polyamine effect, indicating that the inhibition of mast cell secretion must derive from aldehydes produced from these polyamines. Addition of the aldehyde inhibitor phenylhydrazine (phi-HDZ), simultaneously with, but not following the polyamines, blocked their inhibitory effect, further strengthening the involvement of aldehydes. These results indicate that naturally occurring polyamines may regulate mast cell secretion through metabolic products of polyamine oxidase, a similar enzyme of which is also present in human liver, placenta and pregnant serum.

  16. Galactoxylomannan-mediated immunological paralysis results from specific B cell depletion in the context of widespread immune system damage

    PubMed Central

    De Jesus, Magdia; Nicola, André Moraes; Frases, Susana; Lee, Ian R.; Mieses, Steven; Casadevall, Arturo

    2009-01-01

    The mechanisms responsible for polysaccharide-induced immunological paralysis have remained unexplained almost a century after this phenomenon was first described. Cryptococcus neoformans capsular polysaccharides glucuronoxylomannan (GXM) and galactoxylomannan (GalXM) elicit little or no antibody responses. This study investigates the immunological and biological effects of GalXM in mice. GalXM immunization elicits a state of immunological paralysis in mice characterized by the disappearance of antibody-producing cells in the spleen. Immunological paralysis and lack of immunogenicity could not be overcome by immunization with GalXM conjugated to a protein carrier, Bacillus anthracis protective antigen. Additionally, immunization with GalXM in either complete or incomplete Freund's adjuvant was associated with spleen enlargement in Balb/c mice. Terminal deoxynucleotidyl Transferase Biotin-dUTP Nick End Labeling (TUNEL) and flow cytometry revealed widespread apoptosis in the spleen after GalXM administration. Administration of a cocktail of Caspase-3 Inhibitor Z-DEVD-FMK and General Caspase Inhibitor Z-VAD-FMK or Fas-deficient mice abrogated the complete disappearance of antibody producing cells. Analysis of spleen cytokine expression in response to GalXM systemic injection revealed that GalXM down-regulated the production of inflammatory cytokines. Hence, we conclude that GalXM-induced immune paralysis is a result of specific B-cell depletion mediated by its pro-apoptotic properties in the context of widespread dysregulation of immune function. PMID:19684080

  17. Galactoxylomannan-mediated immunological paralysis results from specific B cell depletion in the context of widespread immune system damage.

    PubMed

    De Jesus, Magdia; Nicola, André Moraes; Frases, Susana; Lee, Ian R; Mieses, Steven; Casadevall, Arturo

    2009-09-15

    The mechanisms responsible for polysaccharide-induced immunological paralysis have remained unexplained almost a century after this phenomenon was first described. Cryptococcus neoformans capsular polysaccharides glucuronoxylomannan and galactoxylomannan (GalXM) elicit little or no Ab responses. This study investigates the immunological and biological effects of GalXM in mice. GalXM immunization elicits a state of immunological paralysis in mice characterized by the disappearance of Ab-producing cells in the spleen. Immunological paralysis and lack of immunogenicity could not be overcome by immunization with GalXM conjugated to a protein carrier, Bacillus anthracis protective Ag. Additionally, immunization with GalXM in either complete or IFA was associated with spleen enlargement in BALB/c mice. TUNEL and flow cytometry revealed widespread apoptosis in the spleen after GalXM administration. Administration of a cocktail of caspase-3 inhibitor Z-DEVD-FMK and general caspase inhibitor Z-VAD-FMK or Fas-deficient mice abrogated the complete disappearance of Ab-producing cells. Analysis of spleen cytokine expression in response to GalXM systemic injection revealed that GalXM down-regulated the production of inflammatory cytokines. Hence, we conclude that GalXM-induced immune paralysis is a result of specific B cell depletion mediated by its proapoptotic properties in the context of widespread dysregulation of immune function.

  18. B cell depletion therapy in systemic lupus erythematosus: long‐term follow‐up and predictors of response

    PubMed Central

    Ng, Kristine P; Cambridge, Geraldine; Leandro, Maria J; Edwards, Jonathan C W; Ehrenstein, Michael; Isenberg, David A

    2007-01-01

    Objectives To describe the long‐term clinical outcome and safety profile of B cell depletion therapy (BCDT) in patients with systemic lupus erythematosus (SLE). It was also determined whether baseline parameters can predict the likelihood of disease flare. Methods 32 patients with refractory SLE were treated with BCDT using a combination protocol (rituximab and cyclo‐phosphamide). Patients were assessed with the British Isles Lupus Assessment Group (BILAG) activity index, and baseline serology was measured. Flare was defined as a new BILAG ‘A' or two new subsequent ‘B's in any organ system. Results Of the 32 patients, 12 have remained well after one cycle of BCDT (median follow‐up 39 months). BCDT was followed by a decrease of median global BILAG scores from 13 to 5 at 6 months (p = 0.006). Baseline anti‐extractable nuclear antigen (ENA) was the only identified independent predictor of flare post‐BCDT (p = 0.034, odds ratio = 8, 95% CI 1.2 to 55) from multivariable analysis. Patients with low baseline serum C3 had a shorter time to flare post‐BCDT (p = 0.008). Four serious adverse events were observed. Conclusion Autoantibody profiling may help identify patients who will have a more sustained response. Although the long‐term safety profile of BCDT is favourable, ongoing vigilance is recommended. PMID:17412738

  19. Survival after T cell-depleted haploidentical stem cell transplantation is improved using the mother as donor.

    PubMed

    Stern, Martin; Ruggeri, Loredana; Mancusi, Antonella; Bernardo, Maria Ester; de Angelis, Claudia; Bucher, Christoph; Locatelli, Franco; Aversa, Franco; Velardi, Andrea

    2008-10-01

    We hypothesized that transplacental leukocyte trafficking during pregnancy, which induces long-term, stable, reciprocal microchimerism in mother and child, might influence outcome of patients with acute leukemia given parental donor haploidentical hematopoietic stem cell transplantation (HSCT). We analyzed the outcome of 118 patients who received transplants for acute leukemia in 2 centers. Patients received highly T cell-depleted haploidentical grafts after myelo-ablative conditioning. Five-year event-free survival was better in patients who received transplants from the mother than from the father (50.6% +/- 7.6% vs 11.1% +/- 4.2%; P < .001). Better survival was the result of both reduced incidence of relapse and transplantation-related mortality. The protective effect was seen in both female and male recipients, in both lymphoid and myeloid diseases; it was more evident in patients receiving transplants in remission than in chemotherapy-resistant relapse. Incidences of rejection and acute graft-versus-host disease were not significantly influenced. Multivariate analysis confirmed donor sex in parental donor transplantation as an independent prognostic factor for survival (hazard ratio, father vs mother = 2.36; P = .003). In contrast, in a control cohort of patients who received transplants from haploidentical siblings, donor sex had no influence on outcome. Although obtained in a retrospective analysis, these data suggest that the mother of the patient should be preferred as donor for haploidentical HSCT. PMID:18492955

  20. Prevention of immunodeficiency virus induced CD4+ T-cell depletion by prior infection with a non-pathogenic virus

    SciTech Connect

    TerWee, Julie A.; Carlson, Jennifer K.; Sprague, Wendy S.; Sondgeroth, Kerry S.; Shropshire, Sarah B.; Troyer, Jennifer L.; VandeWoude, Sue

    2008-07-20

    Immune dysregulation initiated by a profound loss of CD4+ T-cells is fundamental to HIV-induced pathogenesis. Infection of domestic cats with a non-pathogenic lentivirus prevalent in the puma (puma lentivirus, PLV or FIV{sub PCO}) prevented peripheral blood CD4+ T-cell depletion caused by subsequent virulent FIV infection. Maintenance of this critical population was not associated with a significant decrease in FIV viremia, lending support to the hypothesis that direct viral cytopathic effect is not the primary cause of immunodeficiency. Although this approach was analogous to immunization with a modified live vaccine, correlates of immunity such as a serum-neutralizing antibody or virus-specific T-cell proliferative response were not found in protected animals. Differences in cytokine transcription profile, most notably in interferon gamma, were observed between the protected and unprotected groups. These data provide support for the importance of non-adaptive enhancement of the immune response in the prevention of CD4+ T-cell loss.

  1. [Regulatory T cell depletion increases the number of CD8 cells during mouse mammary tumor virus infection].

    PubMed

    Cabrera, Gabriel; Mundiñano, Juliana; Camicia, Gabriela; Costa, Héctor; Nepomnaschy, Irene; Piazzon, Isabel

    2011-01-01

    Mouse mammary tumor virus (MMTV) is a milk-borne betaretrovirus that has developed strategies to exploit and subvert the host immune system. We have shown in a natural model of MMTV infection that the virus causes early and progressive increases in superantigen (Sag)-specific CD4+ CD25+ Foxp3+ regulatory T cells (Treg) in Peyer's patches. Herein, we evaluated whether the depletion of Treg cells affects the CD8+ population during milk-borne MMTV infection. At day 6 of infection, the depletion of Treg cells increased the percentage and absolute number of CD8+ cells in lymph nodes as well as the mean intensity fluorescence of the CD44 activation marker. The absolute number of CD8+ cells was increased in cells bearing both Sag reactive and non-reactive TCR Vβ chains. We have previously shown that regulatory T cell depletion at day 6 of infection decrease viral load. Results reported herein suggest that at least after day 6 of MMTV infection Treg cells play an inhibiting role on CD8 antiviral response. PMID:21745773

  2. The SNARE Machinery in Mast Cell Secretion.

    PubMed

    Lorentz, Axel; Baumann, Anja; Vitte, Joana; Blank, Ulrich

    2012-01-01

    Mast cells are known as inflammatory cells which exert their functions in allergic and anaphylactic reactions by secretion of numerous inflammatory mediators. During an allergic response, the high-affinity IgE receptor, FcεRI, becomes cross-linked by receptor-bound IgE and antigen resulting in immediate release of pre-synthesized mediators - stored in granules - as well as in de novo synthesis of various mediators like cytokines and chemokines. Soluble N-ethylmaleimide-sensitive factor attachment protein (SNAP) receptors (SNARE) proteins were found to play a central role in regulating membrane fusion events during exocytosis. In addition, several accessory regulators like Munc13, Munc18, Rab GTPases, secretory carrier membrane proteins, complexins, or synaptotagmins were found to be involved in membrane fusion. In this review we summarize our current knowledge about the SNARE machinery and its mechanism of action in mast cell secretion.

  3. The mast cell: a multifunctional effector cell.

    PubMed

    Crivellato, Enrico; Ribatti, Domenico; Mallardi, Franco; Beltrami, Carlo Alberto

    2003-01-01

    Mast cells (MC) are recognized key cells of type I hypersensitivity reactions. Several lines of evidence, however, indicate that MC not only express critical effector functions in classic IgE-associated allergic disorders, but also play important roles in host defence against parasites, bacteria and perhaps even viruses. Indeed, it is now clear that MC can contribute to host defence in the context of either acquired or innate immune responses through the release of a myriad of pro-inflammatory and immunoregulatory molecules and the expression of a wide spectrum of surface receptors for cytokines and chemokines. Moreover, there is growing evidence that MC exert distinct nonimmunological functions, playing a relevant role in tissue homeostasis, remodeling and fibrosis as well as in the processes of tissue angiogenesis. In this review, we provide a small insight into the biology of mast cells and their potential implications in human pathology.

  4. Hymenoptera Allergy and Mast Cell Activation Syndromes.

    PubMed

    Bonadonna, Patrizia; Bonifacio, Massimiliano; Lombardo, Carla; Zanotti, Roberta

    2016-01-01

    Mast cell activation syndrome (MCAS) can be diagnosed in patients with recurrent, severe symptoms from mast cell (MC)-derived mediators, which are transiently increased in serum and are attenuated by mediator-targeting drugs. When KIT-mutated, clonal MC are detected in these patients, a diagnosis of primary MCAS can be made. Severe systemic reactions to hymenoptera venom (HV) represent the most common form of anaphylaxis in patients with mastocytosis. Patients with primary MCAS and HV anaphylaxis are predominantly males and do not have skin lesions in the majority of cases, and anaphylaxis is characterized by hypotension and syncope in the absence of urticaria and angioedema. A normal value of tryptase (≤11.4 ng/ml) in these patients does not exclude a diagnosis of mastocytosis. Patients with primary MCAS and HV anaphylaxis have to undergo lifelong venom immunotherapy, in order to prevent further potentially fatal severe reactions. PMID:26714690

  5. The SNARE Machinery in Mast Cell Secretion

    PubMed Central

    Lorentz, Axel; Baumann, Anja; Vitte, Joana; Blank, Ulrich

    2012-01-01

    Mast cells are known as inflammatory cells which exert their functions in allergic and anaphylactic reactions by secretion of numerous inflammatory mediators. During an allergic response, the high-affinity IgE receptor, FcεRI, becomes cross-linked by receptor-bound IgE and antigen resulting in immediate release of pre-synthesized mediators – stored in granules – as well as in de novo synthesis of various mediators like cytokines and chemokines. Soluble N-ethylmaleimide-sensitive factor attachment protein (SNAP) receptors (SNARE) proteins were found to play a central role in regulating membrane fusion events during exocytosis. In addition, several accessory regulators like Munc13, Munc18, Rab GTPases, secretory carrier membrane proteins, complexins, or synaptotagmins were found to be involved in membrane fusion. In this review we summarize our current knowledge about the SNARE machinery and its mechanism of action in mast cell secretion. PMID:22679448

  6. Hymenoptera Allergy and Mast Cell Activation Syndromes.

    PubMed

    Bonadonna, Patrizia; Bonifacio, Massimiliano; Lombardo, Carla; Zanotti, Roberta

    2016-01-01

    Mast cell activation syndrome (MCAS) can be diagnosed in patients with recurrent, severe symptoms from mast cell (MC)-derived mediators, which are transiently increased in serum and are attenuated by mediator-targeting drugs. When KIT-mutated, clonal MC are detected in these patients, a diagnosis of primary MCAS can be made. Severe systemic reactions to hymenoptera venom (HV) represent the most common form of anaphylaxis in patients with mastocytosis. Patients with primary MCAS and HV anaphylaxis are predominantly males and do not have skin lesions in the majority of cases, and anaphylaxis is characterized by hypotension and syncope in the absence of urticaria and angioedema. A normal value of tryptase (≤11.4 ng/ml) in these patients does not exclude a diagnosis of mastocytosis. Patients with primary MCAS and HV anaphylaxis have to undergo lifelong venom immunotherapy, in order to prevent further potentially fatal severe reactions.

  7. MAST Propellant and Delivery System Design Methods

    NASA Technical Reports Server (NTRS)

    Nadeem, Uzair; Mc Cleskey, Carey M.

    2015-01-01

    A Mars Aerospace Taxi (MAST) concept and propellant storage and delivery case study is undergoing investigation by NASA's Element Design and Architectural Impact (EDAI) design and analysis forum. The MAST lander concept envisions landing with its ascent propellant storage tanks empty and supplying these reusable Mars landers with propellant that is generated and transferred while on the Mars surface. The report provides an overview of the data derived from modeling between different methods of propellant line routing (or "lining") and differentiate the resulting design and operations complexity of fluid and gaseous paths based on a given set of fluid sources and destinations. The EDAI team desires a rough-order-magnitude algorithm for estimating the lining characteristics (i.e., the plumbing mass and complexity) associated different numbers of vehicle propellant sources and destinations. This paper explored the feasibility of preparing a mathematically sound algorithm for this purpose, and offers a method for the EDAI team to implement.

  8. Twenty-first century mast cell stabilizers

    PubMed Central

    Finn, D F; Walsh, J J

    2013-01-01

    Mast cell stabilizing drugs inhibit the release of allergic mediators from mast cells and are used clinically to prevent allergic reactions to common allergens. Despite the relative success of the most commonly prescribed mast cell stabilizer, disodium cromoglycate, in use for the preventative treatment of bronchial asthma, allergic conjunctivitis and vernal keratoconjunctivitis, there still remains an urgent need to design new substances that are less expensive and require less frequent dosing schedules. In this regard, recent developments towards the discovery of the next generation of mast cell stabilizing drugs has included studies on substances isolated from natural sources, biological, newly synthesized compounds and drugs licensed for other indications. The diversity of natural products evaluated range from simple phenols, alkaloids, terpenes to simple amino acids. While in some cases their precise mode of action remains unknown it has nevertheless sparked interest in the development of synthetic derivatives with improved pharmacological properties. Within the purely synthetic class of inhibitors, particular attention has been devoted to the inhibition of important signalling molecules including spleen TK and JAK3. The statin class of cholesterol-lowering drugs as well as nilotinib, a TK inhibitor, are just some examples of clinically used drugs that have been evaluated for their anti-allergic properties. Here, we examine each approach under investigation, summarize the test data generated and offer suggestions for further preclinical evaluation before their therapeutic potential can be realized. Linked Articles This article is part of a themed issue on Histamine Pharmacology Update. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2013.170.issue-1 PMID:23441583

  9. Mast cells: multitalented facilitators of protection against bacterial pathogens

    PubMed Central

    Trivedi, Nikita H; Guentzel, M Neal; Rodriguez, Annette R; Yu, Jieh-Juen; Forsthuber, Thomas G; Arulanandam, Bernard P

    2014-01-01

    Mast cells are crucial effector cells evoking immune responses against bacterial pathogens. The positioning of mast cells at the host–environment interface, and the multitude of pathogen-recognition receptors and preformed mediator granules make these cells potentially the earliest to respond to an invading pathogen. In this review, the authors summarize the receptors used by mast cells to recognize invading bacteria and discuss the function of immune mediators released by mast cells in control of bacterial infection. The interaction of mast cells with other immune cells, including macrophages, dendritic cells and T cells, to induce protective immunity is highlighted. The authors also discuss mast cell-based vaccine strategies and the potential application in control of bacterial disease. PMID:23390944

  10. Characterization of Mast Cell Secretory Granules and Their Cell Biology

    PubMed Central

    Azouz, Nurit Pereg; Hammel, Ilan

    2014-01-01

    Exocytosis and secretion of secretory granule (SG) contained inflammatory mediators is the primary mechanism by which mast cells exert their protective immune responses in host defense, as well as their pathological functions in allergic reactions and anaphylaxis. Despite their central role in mast cell function, the molecular mechanisms underlying the biogenesis and secretion of mast cell SGs remain largely unresolved. Early studies have established the lysosomal nature of the mast cell SGs and implicated SG homotypic fusion as an important step occurring during both their biogenesis and compound secretion. However, the molecular mechanisms that account for key features of this process largely remain to be defined. A novel high-resolution imaging based methodology allowed us to screen Rab GTPases for their phenotypic and functional impact and identify Rab networks that regulate mast cell secretion. This screen has identified Rab5 as a novel regulator of homotypic fusion of the mast cell SGs that thereby regulates their size and cargo composition. PMID:24988214

  11. Rosae Multiflorae Fructus Hot Water Extract Inhibits a Murine Allergic Asthma Via the Suppression of Th2 Cytokine Production and Histamine Release from Mast Cells.

    PubMed

    Song, Chang Ho; Bui, Thi Tho; Piao, Chun Hua; Shin, Hee Soon; Shon, Dong-Hwa; Han, Eui-Hyeog; Kim, Hyoung Tae; Chai, Ok Hee

    2016-09-01

    Mast cell-mediated anaphylactic reactions are involved in many allergic diseases, including asthma and allergic rhinitis. In Korea, where it has been used as a traditional medicine, Rosae Multiflorae fructus (RMF) is known to have potent antioxidative, analgesic, and anti-inflammatory activities and to have no obvious acute toxicity. However, its specific effect on asthma is still unknown. In this study, we evaluated whether or not RMF hot water extracts (RMFW) could inhibit ovalbumin (OVA)-induced allergic asthma and evaluated compound 48/80-induced mast cell activation to elucidate the mechanisms of asthma inhibition by RMFW. Oral administration of RMFW decreased the number of eosinophils and lymphocytes in the lungs of mice challenged by OVA and downregulated histological changes such as eosinophil infiltration, mucus accumulation, goblet cell hyperplasia, and collagen fiber deposits. In addition, RMFW significantly reduced T helper 2 cytokines, TNF-α, IL-4, and IL-6 levels in the BAL fluid of mice challenged by OVA. Moreover, RMFW suppressed compound 48/80-induced rat peritoneal mast cell degranulation and inhibited histamine release from mast cells induced by compound 48/80 in a dose-dependent manner. These results suggest that RMFW may act as an antiallergic agent by inhibitingTh2 cytokine production from Th2 cells and histamine release from mast cells, and could be used as a therapy for patients with Th2-mediated or mast cell-mediated allergic diseases. PMID:27574849

  12. Commensal bacteria promote migration of mast cells into the intestine.

    PubMed

    Kunii, Junichi; Takahashi, Kyoko; Kasakura, Kazumi; Tsuda, Masato; Nakano, Kou; Hosono, Akira; Kaminogawa, Shuichi

    2011-06-01

    Mast cells differentiate from hematopoietic stem cells in the bone marrow and migrate via the circulation to peripheral tissues, where they play a pivotal role in induction of both innate and adaptive immune responses. In this study, the effect of intestinal commensal bacteria on the migration of mast cells into the intestine was investigated. Histochemical analyses showed that germ-free (GF) mice had lower mast cell densities in the small intestine than normal mice. It was also shown that GF mice had lower mast cell proportion out of lamina propria leukocytes in the small intestine and higher mast cell percentages in the blood than normal mice by flow cytometry. These results indicate that migration of mast cells from the blood to the intestine is promoted by intestinal commensal bacteria. In addition, MyD88⁻/⁻ mice had lower densities of intestinal mast cells than CV mice, suggesting that the promotive effect of commensals is, at least in part, TLR-dependent. The ligands of CXC chemokine receptor 2 (CXCR2), which is critical for homing of mast cells to the intestine, were expressed higher in intestinal tissues and in intestinal epithelial cells (IECs) of normal mice than in those of GF or MyD88⁻/⁻ mice. Collectively, it is suggested that commensals promote migration of mast cells into the intestine through the induction of CXCR2 ligands from IECs in a TLR-dependent manner.

  13. The effects of aspartame on mast cells and basophils.

    PubMed

    Szucs, E F; Barrett, K E; Metcalfe, D D

    1986-02-01

    The artificial sweetener aspartame was studied to determine whether it had any direct effects on mast cells and basophils. Aspartame was not shown to be a direct mast cell or basophil secretagogue in vitro, or in vivo as assessed by skin testing. During an acute incubation, aspartame did not affect IgE-mediated histamine release from mast cells. However, mast cells cultured in aspartame for periods of up to 9 days showed enhanced rates of proliferation and decreased responsiveness to releasing stimuli. The effect of aspartame on proliferation of cells in culture could be ascribed to a non-specific enhancing effect of its constituent amino acids.

  14. Improved Early Outcomes Using a T Cell Replete Graft Compared with T Cell Depleted Haploidentical Hematopoietic Stem Cell Transplantation

    PubMed Central

    Ciurea, Stefan O.; Mulanovich, Victor; Saliba, Rima M.; Bayraktar, Ulas D.; Jiang, Ying; Bassett, Roland; Wang, Sa A.; Konopleva, Marina; Fernandez-Vina, Marcelo; Montes, Nivia; Bosque, Doyle; Chen, Julianne; Rondon, Gabriela; Alatrash, Gheath; Alousi, Amin; Bashir, Qaiser; Korbling, Martin; Qazilbash, Muzaffar; Parmar, Simrit; Shpall, Elizabeth; Nieto, Yago; Hosing, Chitra; Kebriaei, Partow; Khouri, Issa; Popat, Uday; de Lima, Marcos; Champlin, Richard E.

    2014-01-01

    Haploidentical stem cell transplantation (SCT) has been generally performed using a T cell depleted (TCD) graft; however, a high rate of nonrelapse mortality (NRM) has been reported, particularly in adult patients. We hypothesized that using a T cell replete (TCR) graft followed by effective posttransplantation immunosuppressive therapy would reduce NRM and improve outcomes. We analyzed 65 consecutive adult patients with hematologic malignancies who received TCR (N = 32) or TCD (N = 33) haploidentical transplants. All patients received a preparative regimen consisting of melphalan, fludarabine, and thiotepa. The TCR group received posttransplantation treatment with cyclophosphamide (Cy), tacrolimus (Tac), and mycophenolate mofetil (MMF). Patients with TCD received antithymocyte globulin followed by infusion of CD34+ selected cells with no posttransplantation immunosuppression. The majority of patients in each group had active disease at the time of transplantation. Outcomes are reported for the TCR and TCD recipients, respectively. Engraftment was achieved in 94% versus 81% (P = NS). NRM at 1 year was 16% versus 42% (P = .02). Actuarial overall survival (OS) and progression-free survival (PFS) rates at 1 year posttransplantation were 64% versus 30% (P = .02) and 50% versus 21% (P = .02). The cumulative incidence of grade II–IV acute graft-versus-host disease (aGVHD) was 20% versus 11% (P = .20), and chronic GVHD (cGVHD) 7% versus 18% (P = .03). Improved reconstitution of T cell subsets and a lower rate of infection were observed in the TCR group. These results indicate that a TCR graft followed by effective control of GVHD posttransplantation may lower NRM and improve survival after haploidentical SCT. PMID:22796535

  15. Improved early outcomes using a T cell replete graft compared with T cell depleted haploidentical hematopoietic stem cell transplantation.

    PubMed

    Ciurea, Stefan O; Mulanovich, Victor; Saliba, Rima M; Bayraktar, Ulas D; Jiang, Ying; Bassett, Roland; Wang, Sa A; Konopleva, Marina; Fernandez-Vina, Marcelo; Montes, Nivia; Bosque, Doyle; Chen, Julianne; Rondon, Gabriela; Alatrash, Gheath; Alousi, Amin; Bashir, Qaiser; Korbling, Martin; Qazilbash, Muzaffar; Parmar, Simrit; Shpall, Elizabeth; Nieto, Yago; Hosing, Chitra; Kebriaei, Partow; Khouri, Issa; Popat, Uday; de Lima, Marcos; Champlin, Richard E

    2012-12-01

    Haploidentical stem cell transplantation (SCT) has been generally performed using a T cell depleted (TCD) graft; however, a high rate of nonrelapse mortality (NRM) has been reported, particularly in adult patients. We hypothesized that using a T cell replete (TCR) graft followed by effective posttransplantation immunosuppressive therapy would reduce NRM and improve outcomes. We analyzed 65 consecutive adult patients with hematologic malignancies who received TCR (N = 32) or TCD (N = 33) haploidentical transplants. All patients received a preparative regimen consisting of melphalan, fludarabine, and thiotepa. The TCR group received posttransplantation treatment with cyclophosphamide (Cy), tacrolimus (Tac), and mycophenolate mofetil (MMF). Patients with TCD received antithymocyte globulin followed by infusion of CD34+ selected cells with no posttransplantation immunosuppression. The majority of patients in each group had active disease at the time of transplantation. Outcomes are reported for the TCR and TCD recipients, respectively. Engraftment was achieved in 94% versus 81% (P = NS). NRM at 1 year was 16% versus 42% (P = .02). Actuarial overall survival (OS) and progression-free survival (PFS) rates at 1 year posttransplantation were 64% versus 30% (P = .02) and 50% versus 21% (P = .02). The cumulative incidence of grade II-IV acute graft-versus-host disease (aGVHD) was 20% versus 11% (P = .20), and chronic GVHD (cGVHD) 7% versus 18% (P = .03). Improved reconstitution of T cell subsets and a lower rate of infection were observed in the TCR group. These results indicate that a TCR graft followed by effective control of GVHD posttransplantation may lower NRM and improve survival after haploidentical SCT.

  16. Immunotherapy of Murine Retrovirus-Induced Acquired Immunodeficiency by CD4 T Regulatory Cell Depletion and PD-1 Blockade ▿

    PubMed Central

    Li, Wen; Green, William R.

    2011-01-01

    LP-BM5 retrovirus induces a complex disease featuring an acquired immunodeficiency syndrome termed murine AIDS (MAIDS) in susceptible strains of mice, such as C57BL/6 (B6). CD4 T helper effector cells are required for MAIDS induction and progression of viral pathogenesis. CD8 T cells are not needed for viral pathogenesis, but rather, are essential for protection from disease in resistant strains, such as BALB/c. We have discovered an immunodominant cytolytic T lymphocyte (CTL) epitope encoded in a previously unrecognized LP-BM5 retroviral alternative (+1 nucleotide [nt]) gag translational open reading frame. CTLs specific for this cryptic gag epitope are the basis of protection from LP-BM5-induced immunodeficiency in BALB/c mice, and the inability of B6 mice to mount an anti-gag CTL response appears critical to the initiation and progression of LP-BM5-induced MAIDS. However, uninfected B6 mice primed by LP-BM5-induced tumors can generate CTL responses to an LP-BM5 retrovirus infection-associated epitope(s) that is especially prevalent on such MAIDS tumor cells, indicating the potential to mount a protective CD8 T-cell response. Here, we utilized this LP-BM5 retrovirus-induced disease system to test whether modulation of normal immune down-regulatory mechanisms can alter retroviral pathogenesis. Thus, following in vivo depletion of CD4 T regulatory (Treg) cells and/or selective interruption of PD-1 negative signaling in the CD8 T-cell compartment, retroviral pathogenesis was significantly decreased, with the combined treatment of CD4 Treg cell depletion and PD-1 blockade working in a synergistic fashion to substantially reduce the induction of MAIDS. PMID:21917983

  17. Characterizing the inhibitory action of zinc oxide nanoparticles on allergic-type mast cell activation.

    PubMed

    Feltis, B N; Elbaz, A; Wright, P F A; Mackay, G A; Turney, T W; Lopata, A L

    2015-08-01

    The development of nanoparticles (NPs) for commercial products is undergoing a dramatic expansion. Many sunscreens and cosmetics now use zinc oxide (ZnO) or titania (TiO2) NPs, which are effective ultraviolet (UV) filters. Zinc oxide topical creams are also used in mild anti-inflammatory treatments. In this study we evaluated the effect of size and dispersion state of ZnO and TiO2 NPs, compared to "bulk" ZnO, on mast cell degranulation and viability. ZnO and TiO2 NPs were characterized using dynamic light scattering and disc centrifugation. Rat basophilic leukaemia (RBL-2H3) cells and primary mouse bone marrow-derived mast cells (BMMCs) were exposed to ZnO and TiO2 NPs of different sizes (25-200 nm) and surface coatings at concentrations from 1 to 200 μg/mL. The effect of NPs on immunoglobulin E (IgE)-dependent mast cell degranulation was assessed by measuring release of both β-hexosaminidase and histamine via colorimetric and ELISA assays. The intracellular level of Zn(2+) and Ca(2+) ions were measured using zinquin ethyl ester and Fluo-4 AM fluorescence probes, respectively. Cellular viability was determined using the soluble tetrazolium-based MTS colorimetric assay. Exposure of RBL-2H3 and primary mouse BMMC to ZnO NPs markedly inhibited both histamine and β-hexosaminidase release. This effect was both particle size and dispersion dependent. In contrast, TiO2 NPs did not inhibit the allergic response. These effects were independent of cytotoxicity, which was observed only at high concentrations of ZnO NPs, and was not observed for TiO2 NPs. The inhibitory effects of ZnO NPs on mast cells were inversely proportional to particle size and dispersion status, and thus these NPs may have greater potential than "bulk" zinc in the inhibition of allergic responses.

  18. Anti-allergic effects of Lycopus lucidus on mast cell-mediated allergy model

    SciTech Connect

    Shin, Tae-Yong . E-mail: tyshin@woosuk.ac.kr; Kim, Sang-Hyun; Suk, Kyoungho; Ha, Jeoung-Hee; Kim, InKyeom; Lee, Maan-Gee; Jun, Chang-Duk; Kim, Sang-Yong; Lim, Jong-Pil; Eun, Jae-Soon; Shin, Hye-Young; Kim, Hyung-Min

    2005-12-15

    The current study characterizes the mechanism by which the aqueous extract of Lycopus lucidus Turcz. (Labiatae) (LAE) decreases mast cell-mediated immediate-type allergic reaction. The immediate-type allergic reaction is involved in many allergic diseases such as asthma and allergic rhinitis. LAE has been used as a traditional medicine in Korea and is known to have an anti-inflammatory effect. However, its specific mechanism of action is still unknown. LAE was anally administered to mice for high and fast absorption. LAE inhibited compound 48/80-induced systemic reactions in mice. LAE decreased the local allergic reaction, passive cutaneous anaphylaxis, activated by anti-dinitrophenyl (DNP) IgE antibody. LAE dose-dependently reduced histamine release from rat peritoneal mast cells activated by compound 48/80 or anti-DNP IgE. Furthermore, LAE decreased the secretion of TNF-{alpha} and IL-6 in phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore A23187-stimulated human mast cells. The inhibitory effect of LAE on the pro-inflammatory cytokine was p38 mitogen-activated protein kinase (MAPK) and nuclear factor-{kappa}B (NF-{kappa}B) dependent. LAE attenuated PMA plus A23187-induced degradation of I{kappa}B{alpha} and nuclear translocation of NF-{kappa}B, and specifically blocked activation of p38 MAPK, but not that of c-jun N-terminal kinase and extracellular signal-regulated kinase. Our findings provide evidence that LAE inhibits mast cell-derived immediate-type allergic reactions and involvement of pro-inflammatory cytokines, p38 MAPK, and NF-{kappa}B in these effects.

  19. Activation of human mast cells by retrocyclin and protegrin highlight their immunomodulatory and antimicrobial properties.

    PubMed

    Gupta, Kshitij; Kotian, Akhil; Subramanian, Hariharan; Daniell, Henry; Ali, Hydar

    2015-10-01

    Preclinical evaluation of Retrocyclins (RC-100, RC-101) and Protegrin-1 (PG-1) antimicrobial peptides (AMPs) is important because of their therapeutic potential against bacterial, fungal and viral infections. Human mast cells (HMCs) play important roles in host defense and wound healing but the abilities of retrocyclins and protegrin-1 to harness these functions have not been investigated. Here, we report that chemically synthesized RC-100 and PG-1 caused calcium mobilization and degranulation in HMCs but these responses were not blocked by an inhibitor of formyl peptide receptor-like 1 (FPRL1), a known receptor for AMPs. However, RC-100 and PG-1 induced degranulation in rat basophilic leukemia (RBL-2H3) cells stably expressing Mas related G protein coupled receptor X2 (MrgX2). Chemical synthesis of these AMPs is prohibitively expensive and post-synthesis modifications (cyclization, disulfide bonds, folding) are inadequate for optimal antimicrobial activity. Indeed, we found that synthetic RC-100, which caused mast cell degranulation via MrgX2, did not display any antimicrobial activity. Green-fluorescent protein (GFP)-tagged RC-101 (analog of RC-100) and GFP-tagged PG-1 purified from transgenic plant chloroplasts killed bacteria and induced mast cell degranulation. Furthermore, GFP-PG1 bound specifically to RBL-2H3 cells expressing MrgX2. These findings suggest that retrocyclins and protegrins activate HMCs independently of FPRL1 but via MrgX2. Harnessing this novel feature of AMPs to activate mast cell's host defense/wound healing properties in addition to their antimicrobial activities expands their clinical potential. Low cost production of AMPs in plants should facilitate their advancement to the clinic overcoming major hurdles in current production systems. PMID:26378047

  20. Overview of physics results from MAST

    NASA Astrophysics Data System (ADS)

    Lloyd, B.; Akers, R. J.; Alladio, F.; Allan, S.; Appel, L. C.; Barnes, M.; Barratt, N. C.; Ben Ayed, N.; Breizman, B. N.; Cecconello, M.; Challis, C. D.; Chapman, I. T.; Ciric, D.; Colyer, G.; Connor, J. W.; Conway, N. J.; Cox, M.; Cowley, S. C.; Cunningham, G.; Darke, A.; De Bock, M.; Delchambre, E.; De Temmerman, G.; Dendy, R. O.; Denner, P.; Driscoll, M. D.; Dudson, B.; Dunai, D.; Dunstan, M.; Elmore, S.; Field, A. R.; Fishpool, G.; Freethy, S.; Garzotti, L.; Gibson, K. J.; Gryaznevich, M. P.; Guttenfelder, W.; Harrison, J.; Hastie, R. J.; Hawkes, N. C.; Hender, T. C.; Hnat, B.; Howell, D. F.; Hua, M.-D.; Hubbard, A.; Huysmans, G.; Keeling, D.; Kim, Y. C.; Kirk, A.; Liang, Y.; Lilley, M. K.; Lisak, M.; Lisgo, S.; Liu, Y. Q.; Maddison, G. P.; Maingi, R.; Manhood, S. J.; Martin, R.; McArdle, G. J.; McCone, J.; Meyer, H.; Michael, C.; Mordijck, S.; Morgan, T.; Morris, A. W.; Muir, D. G.; Nardon, E.; Naylor, G.; O'Brien, M. R.; O'Gorman, T.; Páleník, J.; Patel, A.; Pinches, S. D.; Price, M. N.; Roach, C. M.; Rozhansky, V.; Saarelma, S.; Sabbagh, S. A.; Saveliev, A.; Scannell, R.; Sharapov, S. E.; Shevchenko, V.; Shibaev, S.; Stork, D.; Storrs, J.; Suttrop, W.; Sykes, A.; Tamain, P.; Taylor, D.; Temple, D.; Thomas-Davies, N.; Thornton, A.; Turnyanskiy, M. R.; Valovic, M.; Vann, R. G. L.; Voss, G.; Walsh, M. J.; Warder, S. E. V.; Wilson, H. R.; Windridge, M.; Wisse, M.; Zoletnik, S.; MAST, the; NBI Teams.

    2011-09-01

    Major developments on the Mega Amp Spherical Tokamak (MAST) have enabled important advances in support of ITER and the physics basis of a spherical tokamak (ST) based component test facility (CTF), as well as providing new insight into underlying tokamak physics. For example, L-H transition studies benefit from high spatial and temporal resolution measurements of pedestal profile evolution (temperature, density and radial electric field) and in support of pedestal stability studies the edge current density profile has been inferred from motional Stark effect measurements. The influence of the q-profile and E × B flow shear on transport has been studied in MAST and equilibrium flow shear has been included in gyro-kinetic codes, improving comparisons with the experimental data. H-modes exhibit a weaker q and stronger collisionality dependence of heat diffusivity than implied by IPB98(y,2) scaling, which may have important implications for the design of an ST-based CTF. ELM mitigation, an important issue for ITER, has been demonstrated by applying resonant magnetic perturbations (RMPs) using both internal and external coils, but full stabilization of type-I ELMs has not been observed. Modelling shows the importance of including the plasma response to the RMP fields. MAST plasmas with q > 1 and weak central magnetic shear regularly exhibit a long-lived saturated ideal internal mode. Measured plasma braking in the presence of this mode compares well with neo-classical toroidal viscosity theory. In support of basic physics understanding, high resolution Thomson scattering measurements are providing new insight into sawtooth crash dynamics and neo-classical tearing mode critical island widths. Retarding field analyser measurements show elevated ion temperatures in the scrape-off layer of L-mode plasmas and, in the presence of type-I ELMs, ions with energy greater than 500 eV are detected 20 cm outside the separatrix. Disruption mitigation by massive gas injection has

  1. Overview of physics results from MAST

    SciTech Connect

    Lloyd, B.; Akers, R. J.; Alladio, F.; Appel, L. C.; Barnes, M.; Barratt, N. C.; Ben Ayed, N.; Breizman, B. N.; Cecconello, M.; Challis, C. D.; Chapman, I. T.; Ciric, D.; Colyer, G.; Connor, J. W.; Conway, N. J.; Cox, M.; Cowley, S. C.; Cunningham, G.; Darke, A.; De Bock, M.; Delchambre, E.; De Temmerman, G.; Dendy, R. O.; Denner, P.; Driscoll, M.; Dudson, B.; Dunai, D.; Dunstan, M.; Elmore, S.; Field, A. R.; Fishpool, G.; Freethy, S.; Garzotti, L.; Gibson, K. J.; Gryaznevich, M. P.; Guttenfelder, W.; Harrison, J.; Hastie, R.; Hawkes, N. C.; Hender, T. C.; Hnat, B.; Howell, D. F.; Hua, M. D.; Hubbard, A.; Huysmans, G.; Keeling, D.; Kim, Y. C.; Kirk, A.; Liang, Y.; Lilley, M.; et al.

    2011-01-01

    Major developments on the Mega Amp Spherical Tokamak (MAST) have enabled important advances in support of ITER and the physics basis of a spherical tokamak (ST) based component test facility (CTF), as well as providing new insight into underlying tokamak physics. For example, L H transition studies benefit from high spatial and temporal resolution measurements of pedestal profile evolution (temperature, density and radial electric field) and in support of pedestal stability studies the edge current density profile has been inferred from motional Stark effect measurements. The influence of the q-profile and E B flow shear on transport has been studied in MAST and equilibrium flow shear has been included in gyro-kinetic codes, improving comparisons with the experimental data. H-modes exhibit a weaker q and stronger collisionality dependence of heat diffusivity than implied by IPB98(y,2) scaling, which may have important implications for the design of an ST-based CTF. ELM mitigation, an important issue for ITER, has been demonstrated by applying resonant magnetic perturbations (RMPs) using both internal and external coils, but full stabilization of type-I ELMs has not been observed. Modelling shows the importance of including the plasma response to the RMP fields. MAST plasmas with q > 1 and weak central magnetic shear regularly exhibit a long-lived saturated ideal internal mode. Measured plasma braking in the presence of this mode compares well with neo-classical toroidal viscosity theory. In support of basic physics understanding, high resolution Thomson scattering measurements are providing new insight into sawtooth crash dynamics and neo-classical tearing mode critical island widths. Retarding field analyser measurements show elevated ion temperatures in the scrape-off layer of L-mode plasmas and, in the presence of type-I ELMs, ions with energy greater than 500 eV are detected 20 cm outside the separatrix. Disruption mitigation by massive gas injection has

  2. 123. UMBILICAL MAST PUMP ROOM (209), LSB (BLDG. 751). PUMP ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    123. UMBILICAL MAST PUMP ROOM (209), LSB (BLDG. 751). PUMP ON LEFT; HYDRAULIC CONTROL PANEL FOR UMBILICAL MAST AND TRENCH DOORS IN CENTER OF ROOM, FACING WEST. - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 East, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

  3. Mast cell function: a new vision of an old cell.

    PubMed

    da Silva, Elaine Zayas Marcelino; Jamur, Maria Célia; Oliver, Constance

    2014-10-01

    Since first described by Paul Ehrlich in 1878, mast cells have been mostly viewed as effectors of allergy. It has been only in the past two decades that mast cells have gained recognition for their involvement in other physiological and pathological processes. Mast cells have a widespread distribution and are found predominantly at the interface between the host and the external environment. Mast cell maturation, phenotype and function are a direct consequence of the local microenvironment and have a marked influence on their ability to specifically recognize and respond to various stimuli through the release of an array of biologically active mediators. These features enable mast cells to act as both first responders in harmful situations as well as to respond to changes in their environment by communicating with a variety of other cells implicated in physiological and immunological responses. Therefore, the critical role of mast cells in both innate and adaptive immunity, including immune tolerance, has gained increased prominence. Conversely, mast cell dysfunction has pointed to these cells as the main offenders in several chronic allergic/inflammatory disorders, cancer and autoimmune diseases. This review summarizes the current knowledge of mast cell function in both normal and pathological conditions with regards to their regulation, phenotype and role.

  4. Involvement of mast cells in adipose tissue fibrosis.

    PubMed

    Hirai, Shizuka; Ohyane, Chie; Kim, Young-Il; Lin, Shan; Goto, Tsuyoshi; Takahashi, Nobuyuki; Kim, Chu-Sook; Kang, Jihey; Yu, Rina; Kawada, Teruo

    2014-02-01

    Recently, fibrosis is observed in obese adipose tissue; however, the pathogenesis remains to be clarified. Obese adipose tissue is characterized by chronic inflammation with massive accumulation of immune cells including mast cells. The objective of the present study was to clarify the relationship between fibrosis and mast cells in obese adipose tissue, as well as to determine the origin of infiltrating mast cells. We observed the enhancement of mast cell accumulation and fibrosis in adipose tissue of severely obese diabetic db/db mice. Furthermore, adipose tissue-conditioned medium (ATCM) from severely obese diabetic db/db mice significantly enhanced collagen 5 mRNA expression in NIH-3T3 fibroblasts, and this enhancement was suppressed by the addition of an anti-mast cell protease 6 (MCP-6) antibody. An in vitro study showed that only collagen V among various types of collagen inhibited preadipocyte differentiation. Moreover, we found that ATCM from the nonobese but not obese stages of db/db mice significantly enhanced the migration of bone marrow-derived mast cells (BMMCs). These findings suggest that immature mast cells that infiltrate into adipose tissue at the nonobese stage gradually mature with the progression of obesity and diabetes and that MCP-6 secreted from mature mast cells induces collagen V expression in obese adipose tissue, which may contribute to the process of adipose tissue fibrosis. Induction of collagen V by MCP-6 might accelerate insulin resistance via the suppression of preadipocyte differentiation.

  5. 109. REDUNDANCY SYSTEM CONTROLS FOR UMBILICAL MAST RETRACTION AT LOWER ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    109. REDUNDANCY SYSTEM CONTROLS FOR UMBILICAL MAST RETRACTION AT LOWER LEFT SIDE OF HYDRAULIC CONTROL PANEL IN UMBILICAL MAST PUMP ROOM (109), LSB (BLDG. 770) - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 West, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

  6. 126. REDUNDANCY SYSTEM CONTROLS FOR UMBILICAL MAST RETRACTION AT LOWER ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    126. REDUNDANCY SYSTEM CONTROLS FOR UMBILICAL MAST RETRACTION AT LOWER LEFT SIDE OF HYDRAULIC CONTROL PANEL IN UMBILICAL MAST PUMP ROOM (209), LSB (BLDG. 751) - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 East, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

  7. Mast cells aggravate sepsis by inhibiting peritoneal macrophage phagocytosis

    PubMed Central

    Dahdah, Albert; Gautier, Gregory; Attout, Tarik; Fiore, Frédéric; Lebourdais, Emeline; Msallam, Rasha; Daëron, Marc; Monteiro, Renato C.; Benhamou, Marc; Charles, Nicolas; Davoust, Jean; Blank, Ulrich; Malissen, Bernard; Launay, Pierre

    2014-01-01

    Controlling the overwhelming inflammatory reaction associated with polymicrobial sepsis remains a prevalent clinical challenge with few treatment options. In septic peritonitis, blood neutrophils and monocytes are rapidly recruited into the peritoneal cavity to control infection, but the role of resident sentinel cells during the early phase of infection is less clear. In particular, the influence of mast cells on other tissue-resident cells remains poorly understood. Here, we developed a mouse model that allows both visualization and conditional ablation of mast cells and basophils to investigate the role of mast cells in severe septic peritonitis. Specific depletion of mast cells led to increased survival rates in mice with acute sepsis. Furthermore, we determined that mast cells impair the phagocytic action of resident macrophages, thereby allowing local and systemic bacterial proliferation. Mast cells did not influence local recruitment of neutrophils and monocytes or the release of inflammatory cytokines. Phagocytosis inhibition by mast cells involved their ability to release prestored IL-4 within 15 minutes after bacterial encounter, and treatment with an IL-4–neutralizing antibody prevented this inhibitory effect and improved survival of septic mice. Our study uncovers a local crosstalk between mast cells and macrophages during the early phase of sepsis development that aggravates the outcome of severe bacterial infection. PMID:25180604

  8. Marine asset security and tracking (MAST) system

    DOEpatents

    Hanson, Gregory Richard; Smith, Stephen Fulton; Moore, Michael Roy; Dobson, Eric Lesley; Blair, Jeffrey Scott; Duncan, Christopher Allen; Lenarduzzi, Roberto

    2008-07-01

    Methods and apparatus are described for marine asset security and tracking (MAST). A method includes transmitting identification data, location data and environmental state sensor data from a radio frequency tag. An apparatus includes a radio frequency tag that transmits identification data, location data and environmental state sensor data. Another method includes transmitting identification data and location data from a radio frequency tag using hybrid spread-spectrum modulation. Another apparatus includes a radio frequency tag that transmits both identification data and location data using hybrid spread-spectrum modulation.

  9. A practical method to evaluate radiofrequency exposure of mast workers.

    PubMed

    Alanko, Tommi; Hietanen, Maila

    2008-01-01

    Assessment of occupational exposure to radiofrequency (RF) fields in telecommunication transmitter masts is a challenging task. For conventional field strength measurements using manually operated instruments, it is difficult to document the locations of measurements while climbing up a mast. Logging RF dosemeters worn by the workers, on the other hand, do not give any information about the location of the exposure. In this study, a practical method was developed and applied to assess mast workers' exposure to RF fields and the corresponding location. This method uses a logging dosemeter for personal RF exposure evaluation and two logging barometers to determine the corresponding height of the worker's position on the mast. The procedure is not intended to be used for compliance assessments, but to indicate locations where stricter assessments are needed. The applicability of the method is demonstrated by making measurements in a TV and radio transmitting mast.

  10. Alterations in MAST suit pressure with changes in ambient temperature.

    PubMed

    Sanders, A B; Meislin, H W; Daub, E

    1983-01-01

    A study was undertaken to test the hypothesis that change in ambient air temperature has an effect on MAST suit pressure according to the ideal gas law. Two different MAST suits were tested on Resusci-Annie dummies. The MAST suits were applied in a cold room at 4.4 degrees C and warmed to 44 degrees C. Positive linear correlations were found in nine trials, but the two suits differed in their rate of increase in pressure. Three trials using humans were conducted showing increased pressure with temperature but at a lesser rate than with dummies. A correlation of 0.5 to 1.0 mm Hg increase in MAST suit pressure for each 1.0 degrees C increase in ambient temperature was found. Implications are discussed for the use of the MAST suit in environmental conditions where the temperature changes. PMID:6679851

  11. Roles and relevance of mast cells in infection and vaccination

    PubMed Central

    Fang, Yu; Xiang, Zou

    2016-01-01

    Abstract In addition to their well-established role in allergy mast cells have been described as contributing to functional regulation of both innate and adaptive immune responses in host defense. Mast cells are of hematopoietic origin but typically complete their differentiation in tissues where they express immune regulatory functions by releasing diverse mediators and cytokines. Mast cells are abundant at mucosal tissues which are portals of entry for common infectious agents in addition to allergens. Here, we review the current understanding of the participation of mast cells in defense against infection. We also discuss possibilities of exploiting mast cell activation to provide adequate adjuvant activity that is needed in high-quality vaccination against infectious diseases. PMID:26565602

  12. A practical method to evaluate radiofrequency exposure of mast workers.

    PubMed

    Alanko, Tommi; Hietanen, Maila

    2008-01-01

    Assessment of occupational exposure to radiofrequency (RF) fields in telecommunication transmitter masts is a challenging task. For conventional field strength measurements using manually operated instruments, it is difficult to document the locations of measurements while climbing up a mast. Logging RF dosemeters worn by the workers, on the other hand, do not give any information about the location of the exposure. In this study, a practical method was developed and applied to assess mast workers' exposure to RF fields and the corresponding location. This method uses a logging dosemeter for personal RF exposure evaluation and two logging barometers to determine the corresponding height of the worker's position on the mast. The procedure is not intended to be used for compliance assessments, but to indicate locations where stricter assessments are needed. The applicability of the method is demonstrated by making measurements in a TV and radio transmitting mast. PMID:19054796

  13. Monitoring of immune cell response to B cell depletion therapy and nerve root injury using SPIO enhanced MRI

    NASA Astrophysics Data System (ADS)

    Thorek, Daniel L.

    2009-12-01

    Magnetic resonance (MR) is a robust platform for non-invasive, high-resolution anatomical imaging. However, MR imaging lacks the requisite sensitivity and contrast for imaging at the cellular level. This represents a clinical impediment to greater diagnostic accuracy. Recent advances have allowed for the in vivo visualization of populations and even of individual cells using superparamagnetic iron oxide (SPIO) MR contrast agents. These nanoparticles, commonly manifested as a core of a single iron oxide crystal or cluster of crystals coated in a biocompatible shell, function to shorten proton relaxation times. In MR imaging these constructs locally dephase protons, resulting in a decrease in signal (hypointensity) localized to the region of accumulation of SPIO. In the context of immune cell imaging, SPIO can provide insight into the cellular migration patterns, trafficking, temporal dynamics and progression of diseases and their related pathological states. Furthermore, by visualizing the presence and activity of immune cells, SPIO-enabled cellular imaging can help evaluate the efficacy of therapy in immune disorders. This thesis examines the production, modification and application of SPIO in a range of in vitro and in vivo immune-response-relevant cellular systems. The role of different nanoparticle characteristics including diameter, surface charge and concentration are investigated in the labeling of T cells in culture. Following optimization of SPIO loading conditions for lymphocytes, the effect these particles have on the activation of primary B cells are elucidated. B cells are tracked using a variety of modalities, with and without the application of B cell depleting therapy. This is to evaluate the efficacy of SPIO as in vivo marker for B cell distribution. Unmodified SPIO were applied to monitor macrophage infiltration in a transient nerve root compression model, with implications for neck pain diagnosis and treatment. Nanoparticle accumulation and MR

  14. Effects of Thy-1+ cell depletion on the capacity of donor lymphoid cells to induce tolerance across an entire MHC disparity in sublethally irradiated adult hosts

    SciTech Connect

    Pierce, G.E.; Watts, L.M. )

    1989-08-01

    Thy-1+ cell depletion with anti-Thy-1.2 mAb and complement markedly reduced the capacity of C57BL/6J, H-2b bone marrow to establish mixed lymphoid chimerism and induce tolerance to C57BL/6J skin grafts across an entire MHC disparity in BALB/c, H-2d hosts conditioned with sublethal, fractionated 7.5 Gy total-body irradiation. In this model tolerance can be transferred to secondary irradiated BALB/c hosts only by cells of C57BL/6J donor, not host, genotype isolated from the spleens of tolerant hosts. Thy-1+ cell depletion abolished the capacity of C57BL/6J donor cells from tolerant BALB/c host spleens to transfer tolerance. The capacity of semiallogeneic BALB/c x C57BL/6J F1, H-2d/b donor BM and spleen cells to induce chimerism and tolerance to C57BL/6J skin grafts in BALB/c parental hosts was also reduced by Thy-1+ cell depletion. Thus the requirement for donor Thy-1+ cells cannot be explained simply on the basis of alloaggression. It is unlikely that the requisite Thy-1+ cells are nonspecific suppressor cells: Thy-1+ cell depletion had no effect on the slight but significant prolongation of third-party C3H/HeJ, H-2k skin grafts in irradiated BALB/c hosts injected with allogeneic C57BL/6J or semiallogeneic BALB/c x C57BL/6J F1 BM compared to irradiated controls injected with medium only. Furthermore, injections of semiallogeneic F1 spleen cells had no significant effect on the survival of the third-party grafts, although these cells were fully capable of inducing tolerance, and their capacity to induce tolerance was significantly reduced by Thy-1+ cell depletion. The requirement for a specific population of lymphoid cells, i.e. Thy-1+, remains unexplained but suggests that donor cells might play a role in the induction or maintenance of tolerance in this model other than merely providing a circulating source of donor antigens.

  15. Mast cells, angiogenesis, and tumour growth.

    PubMed

    Ribatti, Domenico; Crivellato, Enrico

    2012-01-01

    Accumulation of mast cells (MCs) in tumours was described by Ehrlich in his doctoral thesis. Since this early account, ample evidence has been provided highlighting participation of MCs to the inflammatory reaction that occurs in many clinical and experimental tumour settings. MCs are bone marrow-derived tissue-homing leukocytes that are endowed with a panoply of releasable mediators and surface receptors. These cells actively take part to innate and acquired immune reactions as well as to a series of fundamental functions such as angiogenesis, tissue repair, and tissue remodelling. The involvement of MCs in tumour development is debated. Although some evidence suggests that MCs can promote tumourigenesis and tumour progression, there are some clinical sets as well as experimental tumour models in which MCs seem to have functions that favour the host. One of the major issues linking MCs to cancer is the ability of these cells to release potent pro-angiogenic factors. This review will focus on the most recent acquisitions about this intriguing field of research. This article is part of a Special Issue entitled: Mast cells in inflammation.

  16. SOL Width Scaling in the MAST Tokamak

    NASA Astrophysics Data System (ADS)

    Ahn, Joon-Wook; Counsell, Glenn; Connor, Jack; Kirk, Andrew

    2002-11-01

    Target heat loads are determined in large part by the upstream SOL heat flux width, Δ_h. Considerable effort has been made in the past to develop analytical and empirical scalings for Δh to allow reliable estimates to be made for the next-step device. The development of scalings for a large spherical tokamak (ST) such as MAST is particularly important both for development of the ST concept and for improving the robustness of scalings derived for conventional tokamaks. A first such scaling has been developed in MAST DND plasmas. The scaling was developed by flux-mapping data from the target Langmuir probe arrays to the mid-plane and fitting to key upstream parameters such as P_SOL, bar ne and q_95. In order to minimise the effects of co-linearity, dedicated campaigns were undertaken to explore the widest possible range of each parameter while keeping the remainder as fixed as possible. Initial results indicate a weak inverse dependence on P_SOL and approximately linear dependence on bar n_e. Scalings derived from consideration of theoretical edge transport models and integration with data from conventional devices is under way. The established scaling laws could be used for the extrapolations to the future machine such as Spherical Tokamak Power Plant (STPP). This work is jointly funded by Euratom and UK Department of Trade and Industry. J-W. Ahn would like to recognise the support of a grant from the British Foreign & Commonwealth Office.

  17. What is the physiological function of mast cells?

    PubMed

    Maurer, M; Theoharides, T; Granstein, R D; Bischoff, S C; Bienenstock, J; Henz, B; Kovanen, P; Piliponsky, A M; Kambe, N; Vliagoftis, H; Levi-Schaffer, F; Metz, M; Miyachi, Y; Befus, D; Forsythe, P; Kitamura, Y; Galli, S

    2003-12-01

    Under physiological conditions, skin mast cells preferentially localize around nerves, blood vessels and hair follicles. This observation, which dates back to Paul Ehrlich, intuitively suggests that these enigmatic, multifacetted protagonists of natural immunity are functionally relevant to many more aspects of tissue physiology than just to the generation of inflammatory and vasodilatory responses to IgE-dependent environmental antigens. And yet, for decades, mainstream-mast cell research has been dominated by a focus on the -undisputedly prominent and important - mast cell functions in type I immune responses and in the pathogenesis and management of allergic diseases. Certainly, it is hard to believe that the very large and rather selectively distributed number of mast cells in normal, uninflamed, non-infected, non-traumatized mammalian skin or mucosal tissue simply hanging around there lazily day and night, just wait for the odd allergen or parasite-associated antigen to come by so the mast cell can finally swing into action. Indeed, the past decade has witnessed a renaissance of mast cell research 'beyond allergy', along with a more systematic exploration of the surprisingly wide range of physiological functions that mast cells may be involved in. The current debate sketches many exciting horizons that have recently come into our vision during this intriguing, ongoing search. PMID:14719507

  18. Martian environmental simulation for a deployable lattice mast

    NASA Technical Reports Server (NTRS)

    Warden, Robert M.

    1994-01-01

    The Mars Pathfinder mission (formerly Mars Environmental Survey or MESUR) is scheduled for launch in December 1996 and is designed to place a small lander on the surface of Mars. After impact, the lander unfolds to expose its solar panels and release a miniature rover. Also on board is the Imager for Mars Pathfinder (IMP) binocular camera which is elevated by a deployable mast to obtain a panoramic view of the landing area. The design of this deployable mast is based on similar designs which have a long and successful flight history. In the past when this type of self-deployable mast has been used, a rate limiter has been incorporated to control the speed of deployment. In this application, to reduce weight and complexity, it was proposed to eliminate the rate limiter so that the mast would deploy without restraint. Preliminary tests showed that this type of deployment was possible especially if the deployed length was relatively short, as in this application. Compounding the problem, however, was the requirement to deploy the mast at an angle of up to 30 degrees from vertical. The deployment process was difficult to completely analyze due to the effects of gravitational and inertial loads on the mast and camera during rapid extension. Testing in a realistic manner was imperative to verify the system performance. A deployment test was therefore performed to determine the maximum tilt angle at which the mast could reliably extend and support the camera on Mars. The testing of the deployable mast requires partial gravity compensation to simulate the smaller force of Martian gravity. During the test, mass properties were maintained while weight properties were reduced. This paper describes the testing of a deployable mast in a simulated Martian environment as well as the results of the tests.

  19. Quantification and Localization of Mast Cells in Periapical Lesions

    PubMed Central

    Mahita, VN; Manjunatha, BS; Shah, R; Astekar, M; Purohit, S; Kovvuru, S

    2015-01-01

    Background: Periapical lesions occur in response to chronic irritation in periapical tissue, generally resulting from an infected root canal. Specific etiological agents of induction, participating cell population and growth factors associated with maintenance and resolution of periapical lesions are incompletely understood. Among the cells found in periapical lesions, mast cells have been implicated in the inflammatory mechanism. Aim: Quantifications and the possible role played by mast cells in the periapical granuloma and radicular cyst. Hence, this study is to emphasize the presence (localization) and quantification of mast cells in periapical granuloma and radicular cyst. Materials and Methods: A total of 30 cases and out of which 15 of periapical granuloma and 15 radicular cyst, each along with the case details from the previously diagnosed cases in the department of oral pathology were selected for the study. The gender distribution showed male 8 (53.3%) and females 7 (46.7%) in periapical granuloma cases and male 10 (66.7%) and females 5 (33.3%) in radicular cyst cases. The statistical analysis used was unpaired t-test. Results: Mean mast cell count in periapical granuloma subepithelial and deeper connective tissue, was 12.40 (0.99%) and 7.13 (0.83%), respectively. The mean mast cell counts in subepithelial and deeper connective tissue of radicular cyst were 17.64 (1.59%) and 12.06 (1.33%) respectively, which was statistically significant. No statistical significant difference was noted among males and females. Conclusion: Mast cells were more in number in radicular cyst. Based on the concept that mast cells play a critical role in the induction of inflammation, it is logical to use therapeutic agents to alter mast cell function and secretion, to thwart inflammation at its earliest phases. These findings may suggest the possible role of mast cells in the pathogenesis of periapical lesions. PMID:25861530

  20. [Quantitative analysis for mast cells in obstructive sialadenitis].

    PubMed

    Diao, G X

    1993-03-01

    Quantitative analysis for mast cells in 27 cases of obstructive sialadenitis, 12 cases of approximate normal salivary gland tissues and 5 cases of lymphoepithelial lesion of salivary glands shows that the number of mast cells is slightly increased with the increase of gravity-grade of obstructive sialadenitis and this is closely related to fibrosis of salivary glands and infiltration grade of inflammation cells (dominated by lymphocyte cells), whereas not closely relating to the age change of patients. For the cases of benign lymphoepithelial lesion of salivary glands with malignant changes despite of malignant lymphoma or squamous cell carcinoma the numbers of mast cells are obviously decreased.

  1. Self-anchoring mast for deploying a high-speed submersible mixer in a tank

    DOEpatents

    Cato, Jr., Joseph E.; Shearer, Paul M.; Rodwell, Philip O.

    2004-10-12

    A self-anchoring mast for deploying a high-speed submersible mixer in a tank includes operably connected first and second mast members (20, 22) and a foot member 46 operably connected to the second mast member for supporting the mast in a tank. The second mast member includes a track (36, 38) for slidably receiving a bearing of the mixer to change the orientation of the mixer in the tank.

  2. Self-Anchoring Mast for Deploying a High-Speed Submersible Mixer in a Tank

    SciTech Connect

    Cato, Joseph E. Jr.; Shearer, Paul M.; Rodwell, Philip 0.

    2004-10-12

    A self-anchoring mast for deploying a high-speed submersible mixer in a tank includes operably connected first and second mast members (20, 22) and a foot member 46 operably connected to the second mast member for supporting the mast in a tank. The second mast member includes a track (36, 38) for slidably receiving a bearing of the mixer to change the orientation of the mixer in the tank.

  3. B-cell depletion inhibits arthritis in a collagen-induced arthritis (CIA) model, but does not adversely affect humoral responses in a respiratory syncytial virus (RSV) vaccination model.

    PubMed

    Dunussi-Joannopoulos, Kyri; Hancock, Gerald E; Kunz, Arthur; Hegen, Martin; Zhou, Xiaochuan X; Sheppard, Barbara J; Lamothe, Jennifer; Li, Evelyn; Ma, Hak-Ling; Hamann, Philip R; Damle, Nitin K; Collins, Mary

    2005-10-01

    We report the development of a mouse B cell-depleting immunoconjugate (anti-CD22 monoclonal antibody [mAb] conjugated to calicheamicin) and its in vivo use to characterize the kinetics of CD22+ B-cell depletion and reconstitution in murine primary and secondary lymphoid tissues. The effect of B-cell depletion was further studied in a murine collagen-induced arthritis (CIA) model and a respiratory syncytial virus (RSV) vaccination model. Our results show that (1) the immunoconjugate has B-cell-specific in vitro and in vivo cytotoxicity; (2) B-cell reconstitution starts in the bone marrow and spleen around day 30 after depletion and is completed in all tissues tested by day 50; (3) B-cell depletion inhibits the development of clinical and histologic arthritis in the CIA model; (4) depletion of type II collagen antibody levels is not necessary for clinical and histologic prevention of CIA; and (5) B-cell depletion does not adversely affect memory antibody responses after challenge nor clearance of infectious virus from lungs in the RSV vaccination model. These results demonstrate for the first time that only B-cell reduction but not type II collagen antibody levels correlate with the prevention of arthritis and represent key insights into the role of CD22-targeted B-cell depletion in mouse autoimmunity and vaccination models.

  4. Pancam Mast Assembly on Mars Rover

    NASA Technical Reports Server (NTRS)

    Warden, Robert M.; Cross, Mike; Harvison, Doug

    2004-01-01

    The Pancam Mast Assembly (PMA) for the 2003 Mars Rover is a deployable structure that provides an elevated platform for several cameras. The PMA consists of several mechanisms that enable it to raise the cameras as well as point the cameras in all directions. This paper describes the function of the various mechanisms as well as a description of the mechanisms and some test parameters. Designing these mechanisms to operate on the surface of Mars presented several challenges. Typical spacecraft mechanisms must operate in zero-gravity and high vacuum. These mechanisms needed to be designed to operate in Martian gravity and atmosphere. Testing conditions were a little easier because the mechanisms are not required to operate in a vacuum. All of the materials are vacuum compatible, but the mechanisms were tested in a dry nitrogen atmosphere at various cold temperatures.

  5. Mini-mast CSI testbed user's guide

    NASA Technical Reports Server (NTRS)

    Tanner, Sharon E.; Pappa, Richard S.; Sulla, Jeffrey L.; Elliott, Kenny B.; Miserentino, Robert; Bailey, James P.; Cooper, Paul A.; Williams, Boyd L., Jr.; Bruner, Anne M.

    1992-01-01

    The Mini-Mast testbed is a 20 m generic truss highly representative of future deployable trusses for space applications. It is fully instrumented for system identification and active vibrations control experiments and is used as a ground testbed at NASA-Langley. The facility has actuators and feedback sensors linked via fiber optic cables to the Advanced Real Time Simulation (ARTS) system, where user defined control laws are incorporated into generic controls software. The object of the facility is to conduct comprehensive active vibration control experiments on a dynamically realistic large space structure. A primary goal is to understand the practical effects of simplifying theoretical assumptions. This User's Guide describes the hardware and its primary components, the dynamic characteristics of the test article, the control law implementation process, and the necessary safeguards employed to protect the test article. Suggestions for a strawman controls experiment are also included.

  6. D Ebw Emission Studies in Mast

    NASA Astrophysics Data System (ADS)

    Shevchenko, Vladimir F.; de Bock, Maarten; Freethy, Simon; Vann, Roddy; Saveliev, Alexander N.

    2011-02-01

    Angular scanning of EBW emission (EBE) has been conducted in MAST. From EBE measurements over a range of viewing angles the angular position and orientation of the B-X-O mode conversion (MC) window can be estimated giving the pitch angle of the magnetic field in the MC layer. The radial position of the corresponding MC layer is found from Thomson scattering measurements. Measurements at several frequencies can provide a pitch angle profile. Results of pitch angle profile reconstruction from EBE measurements are presented in comparison with motional Stark effect measurements. Microwave imaging of the B-X-O Me window is proposed as an alternative to the angular scanning. The proposed scheme is based on an imaging phased array of antennas allowing the required angular resolution. Image acquisition time is much shorter than MHD time scales so the EBE imaging can be used for pitch angle measurements even in the presence of MHD activity.

  7. T-cell depletion and autologous stem cell transplantation in the management of tumour stage mycosis fungoides with peripheral blood involvement.

    PubMed

    Olavarria, E; Child, F; Woolford, A; Whittaker, S J; Davis, J G; McDonald, C; Chilcott, S; Spittle, M; Grieve, R J; Stewart, S; Apperley, J F; Russell-Jones, R

    2001-09-01

    Nine patients with tumour stage mycosis fungoides (MF) have been entered into a pilot study of T-cell depletion and autologous stem cell transplantation (SCT). Eight patients had detectable rearrangements of the T-cell receptor (TCR) gamma-gene demonstrated by polymerase chain reaction (PCR)/single-stranded conformation polymorphism (SSCP) in the peripheral blood. The median age was 47 years and the median duration of disease before SCT was 61 months; Peripheral blood progenitor cells were mobilized using high-dose etoposide (1.6 g/m2) and granulocyte colony-stimulating factor (G-CSF). The apheresis products underwent rigorous T-cell depletion with immunomagnetic methods. Double CD34-positive and CD4/CD8-negative selection achieved a median reduction of 3.89 log of T cells. All nine patients have been transplanted. Conditioning included carmustine (BCNU), etoposide and melphalan (BEM) in seven patients and total body irradiation plus etoposide or melphalan in two. Eight patients engrafted promptly and one patient died of septicaemia. All survivors entered complete remission. Seven patients have relapsed at a median of 7 months (2-14) post SCT. However, most patients have relapsed into a less aggressive stage, which has responded to conventional therapy. Four out of seven evaluable patients had detectable TCR rearrangements in the T-cell depleted graft. A T-cell clone was also detected in the peripheral blood before relapse in four cases. Autologous SCT is feasible, safe and can result in complete remission in a significant proportion of patients with tumour stage mycosis fungoides. Despite a short relapse-free survival, most patients achieved good disease control at the time of relapse.

  8. B-cell Depletion and Immunomodulation Prior to Initiation of Enzyme Replacement Therapy Blocks the Immune Response to Acid Alpha Glucosidase in Infantile Onset Pompe Disease

    PubMed Central

    Elder, Melissa E.; Nayak, Sushrusha; Collins, Shelley W.; Lawson, Lee Ann; Kelley, Jeffry S.; Herzog, Roland W.; Modica, Renee F.; Lew, Judy; Lawrence, Robert M.; Byrne, Barry J.

    2014-01-01

    Objectives Pompe disease is a progressive neuromuscular disorder due to acid alpha glucosidase (GAA) deficiency. Cross-reacting immunologic material (CRIM)-negative infants with null GAA mutations have the most severe phenotype and develop anti-GAA antibodies following exposure to enzyme replacement therapy (ERT). Antibodies influence bio-distribution, attenuate the beneficial effects of ERT, and are believed to influence infusion-associated reactions (IARs), which occur in nearly all early-onset patients. We evaluated the potential that B-cell depletion prior to ERT initiation would block GAA antibody responses and improve clinical outcome. Study Design Six Pompe subjects (four CRIM-negative) between 2–8 months of age received rituximab and sirolimus or myophenolate prior to ERT. Four subjects continued to receive sirolimus, every 12-week rituximab and monthly intravenous immunoglobulin for the duration of ERT. Sirolimus trough levels, IgG levels, CD3, CD4, CD8, CD19, CD20, NTproBNP, CK, CK-MB, CRP, platelet, alkaline phosphatase, AST, ALT were measured regularly. Results Immunomodulation achieved B-cell depletion without adverse effects. After 17–36 months of rituximab, sirolimus and ERT, all subjects lacked antibodies against GAA, four continued to gain motor milestones, yet two progressed to require invasive ventilation. Absence of infusion associated reactions allowed accelerated infusion rates. No IARs were observed at standard or accelerated infusion rates. Conclusions B-cell depletion and T-cell immunomodulation in infants naïve to ERT was accomplished safely, eliminated immune responses against GAA, thereby optimizing clinical outcome, however this approach did not necessarily influence sustained independent ventilation. Importantly, study outcomes support the concept of initiating immunomodulation prior to beginning ERT since the study regimen allowed for prompt initiation of treatment. PMID:23601496

  9. Expansion of Activated Peripheral Blood Memory B Cells in Rheumatoid Arthritis, Impact of B Cell Depletion Therapy, and Biomarkers of Response

    PubMed Central

    Adlowitz, Diana G.; Barnard, Jennifer; Biear, Jamie N.; Cistrone, Christopher; Owen, Teresa; Wang, Wensheng; Palanichamy, Arumugam; Ezealah, Ezinma; Campbell, Debbie; Wei, Chungwen; Looney, R. John; Sanz, Inaki; Anolik, Jennifer H.

    2015-01-01

    Although B cell depletion therapy (BCDT) is effective in a subset of rheumatoid arthritis (RA) patients, both mechanisms and biomarkers of response are poorly defined. Here we characterized abnormalities in B cell populations in RA and the impact of BCDT in order to elucidate B cell roles in the disease and response biomarkers. In active RA patients both CD27+IgD- switched memory (SM) and CD27-IgD- double negative memory (DN) peripheral blood B cells contained significantly higher fractions of CD95+ and CD21- activated cells compared to healthy controls. After BCD the predominant B cell populations were memory, and residual memory B cells displayed a high fraction of CD21- and CD95+ compared to pre-depletion indicating some resistance of these activated populations to anti-CD20. The residual memory populations also expressed more Ki-67 compared to pre-treatment, suggesting homeostatic proliferation in the B cell depleted state. Biomarkers of clinical response included lower CD95+ activated memory B cells at depletion time points and a higher ratio of transitional B cells to memory at reconstitution. B cell function in terms of cytokine secretion was dependent on B cell subset and changed with BCD. Thus, SM B cells produced pro-inflammatory (TNF) over regulatory (IL10) cytokines as compared to naïve/transitional. Notably, B cell TNF production decreased after BCDT and reconstitution compared to untreated RA. Our results support the hypothesis that the clinical and immunological outcome of BCDT depends on the relative balance of protective and pathogenic B cell subsets established after B cell depletion and repopulation. PMID:26047509

  10. Deletion of nef slows but does not prevent CD4-positive T-cell depletion in human immunodeficiency virus type 1-infected human-PBL-SCID mice.

    PubMed Central

    Gulizia, R J; Collman, R G; Levy, J A; Trono, D; Mosier, D E

    1997-01-01

    The pathogenicity of four human immunodeficiency virus type 1 (HIV-1) isolates with nef deleted for SCID mice repopulated with human peripheral blood leukocytes (hu-PBL-SCID mice) was studied. Deletion of nef led to a substantial reduction in CD4-positive T-cell depletion and delayed kinetics of plasma viremia in infected hu-PBL-SCID mice. Deletion of the nef gene impacts both the efficiency of primary infection and the cytopathicity of virus for infected CD4-positive T cells in this animal model of HIV-1 infection. PMID:9094701

  11. 47. BASE OF UMBILICAL MAST, WITH ELECTRICAL POWER CABLES ON ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    47. BASE OF UMBILICAL MAST, WITH ELECTRICAL POWER CABLES ON LEFT; AIR-CONDITIONER DUCTS ON RIGHT - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 East, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

  12. 9. DETAIL OF UMBILICAL MAST BASE WITH STEEL STOPS AT ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    9. DETAIL OF UMBILICAL MAST BASE WITH STEEL STOPS AT EAST END OF MOBILE SERVICE STRUCTURE RAIL; VIEW TO NORTHWEST. - Cape Canaveral Air Station, Launch Complex 17, Facility 28501, East end of Lighthouse Road, Cape Canaveral, Brevard County, FL

  13. Assessment of the COFSI/MAST I project

    NASA Technical Reports Server (NTRS)

    Chew, Meng-Sang

    1987-01-01

    The COFS (MAST I) deployer/retractor assembly (DRA) which has a cluster of mechanisms that constitute the collapsible/extensible Mast, contains mechanisms/linkages that deploy and retract. The Mast is a flexible spatial (3D) linkage with hinges that lock into place during deployment to form a truss type structure. It is 60 meters long with repeating sections of two bays. Each bay has alternating diagonals. All joints are single degree-of-freedom hinges, arranged such that the Mast does not rotate during deployment/restow and that deformation energy is minimized. Mispan hinges are incorporated in the diagonals and half of the batten members. The various operational aspects and characteristics of the various mechanisms within the DRA are analyzed. In view of the disadvantages of statical in determinancy as well as the inefficiencies inherent in recirculating gear trains, it is recommended that the bevel gear trains and the bell-crank mechanisms be redesigned.

  14. A poloidal section neutron camera for MAST upgrade

    SciTech Connect

    Sangaroon, S.; Weiszflog, M.; Cecconello, M.; Conroy, S.; Ericsson, G.; Wodniak, I.; Keeling, D.; Turnyanskiy, M. [EURATOM Collaboration: MAST Team

    2014-08-21

    The Mega Ampere Spherical Tokamak Upgrade (MAST Upgrade) is intended as a demonstration of the physics viability of the Spherical Tokamak (ST) concept and as a platform for contributing to ITER/DEMO physics. Concerning physics exploitation, MAST Upgrade plasma scenarios can contribute to the ITER Tokamak physics particularly in the field of fast particle behavior and current drive studies. At present, MAST is equipped with a prototype neutron camera (NC). On the basis of the experience and results from previous experimental campaigns using the NC, the conceptual design of a neutron camera upgrade (NC Upgrade) is being developed. As part of the MAST Upgrade, the NC Upgrade is considered a high priority diagnostic since it would allow studies in the field of fast ions and current drive with good temporal and spatial resolution. In this paper, we explore an optional design with the camera array viewing the poloidal section of the plasma from different directions.

  15. Mast cells in allergy and autoimmunity: implications for adaptive immunity.

    PubMed

    Gregory, Gregory D; Brown, Melissa A

    2006-01-01

    As in the fashion industry, trends in a particular area of scientific investigation often are fleeting but then return with renewed and enthusiastic interest. Studies of mast cell biology are good examples of this. Although dogma once relegated mast cells almost exclusively to roles in pathological inflammation associated with allergic disease, these cells are emerging as important players in a number of other physiological processes. Consequently, they are quickly becoming the newest "trendy" cell, both within and outside the field of immunology. As sources of a large array of pro- and anti-inflammatory mediators, mast cells also express cell surface molecules with defined functions in lymphocyte activation and trafficking. Here, we provide an overview of the traditional and newly appreciated contributions of mast cells to both innate and adaptive immune responses.

  16. 19. DECK VIEW LOOKING FORWARD WITH MAST, RIGGING AND BOWSPRIT ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    19. DECK VIEW LOOKING FORWARD WITH MAST, RIGGING AND BOWSPRIT DETAILS - HATCH COVER REMOVED TO SHOW CENTERBOARD TRUNK - KATHRYN-Two-sail Bateau "Skipjack", Dogwood Harbor, Chesapeake Bay, Tilghman, Talbot County, MD

  17. 51. STERN VIEW AFTER CONVERSION TO AFRAME MAST AND NEW ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    51. STERN VIEW AFTER CONVERSION TO A-FRAME MAST AND NEW CRANE FOR HOISTING BUOYS. - U.S. Coast Guard Cutter WHITE PINE, U.S. Coast Guard 8th District Base, South Broad Street, Mobile, Mobile County, AL

  18. Carbonic anhydrase enzymes regulate mast cell-mediated inflammation.

    PubMed

    Henry, Everett K; Sy, Chandler B; Inclan-Rico, Juan M; Espinosa, Vanessa; Ghanny, Saleena S; Dwyer, Daniel F; Soteropoulos, Patricia; Rivera, Amariliz; Siracusa, Mark C

    2016-08-22

    Type 2 cytokine responses are necessary for the development of protective immunity to helminth parasites but also cause the inflammation associated with allergies and asthma. Recent studies have found that peripheral hematopoietic progenitor cells contribute to type 2 cytokine-mediated inflammation through their enhanced ability to develop into mast cells. In this study, we show that carbonic anhydrase (Car) enzymes are up-regulated in type 2-associated progenitor cells and demonstrate that Car enzyme inhibition is sufficient to prevent mouse mast cell responses and inflammation after Trichinella spiralis infection or the induction of food allergy-like disease. Further, we used CRISPR/Cas9 technology and illustrate that genetically editing Car1 is sufficient to selectively reduce mast cell development. Finally, we demonstrate that Car enzymes can be targeted to prevent human mast cell development. Collectively, these experiments identify a previously unrecognized role for Car enzymes in regulating mast cell lineage commitment and suggest that Car enzyme inhibitors may possess therapeutic potential that can be used to treat mast cell-mediated inflammation. PMID:27526715

  19. Mast cells: new therapeutic target in helminth immune modulation.

    PubMed

    Vukman, K V; Lalor, R; Aldridge, A; O'Neill, S M

    2016-01-01

    Helminth infection and their secreted antigens have a protective role in many immune-mediated inflammatory disorders such as inflammatory bowel disease, rheumatoid arthritis and multiple sclerosis. However, studies have focused primarily on identifying immune protective mechanisms of helminth infection and their secreted molecules on dendritic cells and macrophages. Given that mast cells have been shown to be implicated in the pathogenesis and progression of many inflammatory disorders, their role should also be examined and considered as cellular target for helminth-based therapies. As there is a dearth of studies examining the interaction of helminth-derived antigens and mast cells, this review will focus on the role of mast cells during helminth infection and examine our current understanding of the involvement of mast cells in TH 1/TH 17-mediated immune disorders. In this context, potential mechanisms by which helminths could target the TH 1/TH 17 promoting properties of mast cells can be identified to unveil novel therapeutic mast cell driven targets in combating these inflammatory disorders. PMID:26577605

  20. Mast Cell-Derived Histamine Mediates Cystitis Pain

    PubMed Central

    Rudick, Charles N.; Bryce, Paul J.; Guichelaar, Laura A.; Berry, Ruth E.; Klumpp, David J.

    2008-01-01

    Background Mast cells trigger inflammation that is associated with local pain, but the mechanisms mediating pain are unclear. Interstitial cystitis (IC) is a bladder disease that causes debilitating pelvic pain of unknown origin and without consistent inflammation, but IC symptoms correlate with elevated bladder lamina propria mast cell counts. We hypothesized that mast cells mediate pelvic pain directly and examined pain behavior using a murine model that recapitulates key aspects of IC. Methods and Findings Infection of mice with pseudorabies virus (PRV) induces a neurogenic cystitis associated with lamina propria mast cell accumulation dependent upon tumor necrosis factor alpha (TNF), TNF-mediated bladder barrier dysfunction, and pelvic pain behavior, but the molecular basis for pelvic pain is unknown. In this study, both PRV-induced pelvic pain and bladder pathophysiology were abrogated in mast cell-deficient mice but were restored by reconstitution with wild type bone marrow. Pelvic pain developed normally in TNF- and TNF receptor-deficient mice, while bladder pathophysiology was abrogated. Conversely, genetic or pharmacologic disruption of histamine receptor H1R or H2R attenuated pelvic pain without altering pathophysiology. Conclusions These data demonstrate that mast cells promote cystitis pain and bladder pathophysiology through the separable actions of histamine and TNF, respectively. Therefore, pain is independent of pathology and inflammation, and histamine receptors represent direct therapeutic targets for pain in IC and other chronic pain conditions. PMID:18461160

  1. Clonal T-cell colony formation in agar culture: an attractive assay to test the T-cell depletion from bone marrow.

    PubMed

    Farcet, J P; Beaujean, F; Cordonnier, C; Pico, J; Gourdin, M F; Divine, M; Bracq, C; Bouguet, J; Laurent, G; Bernard, A

    1986-12-01

    Current studies suggest that the depletion of T-lymphocytes from donor marrow is an effective method for preventing acute graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation in man. To deplete the T-lymphocytes from bone marrow cells we use either monoclonal anti-T-cell antibodies and complement or T101 ricin A-chain immunotoxin. Residual T-lymphocytes are analyzed by their capacity to form clonal T-cell colonies in the presence of phytohemagglutinin (PHA), accessory cells, and recombinant interleukin 2. The method is compared to immediate indirect immunofluorescence (iF) and thymidine incorporation by marrow cells stimulated by PHA. IF is not suitable for evaluating the depletion by immunotoxin, and the interpretation of thymidine incorporation is generally questionable. The results of the colony formation show that the sensitivity of the colony assay is close to that of iF when T cells are depleted by complement lysis, and the sensitivity of the colony assay is not dependent upon the depletion procedure. Therefore, the T-cell colony assay is a simple functional control for the quality of bone marrow T-cell depletion, especially for T-cell depletion by immunotoxin. PMID:3536543

  2. Dynamic mast cell-stromal cell interactions promote growth of pancreatic cancer

    PubMed Central

    Ma, Ying; Hwang, Rosa F.; Logsdon, Craig D.; Ullrich, Stephen E.

    2013-01-01

    Pancreatic ductal adenocarcinoma (PDAC) exists in a complex desmoplastic microenvironment, which includes cancer-associated fibroblasts (also known as pancreatic stellate cells, PSCs) and immune cells that provide a fibrotic niche that impedes successful cancer therapy. We have found that mast cells are essential for PDAC tumorigenesis. Whether mast cells contribute to the growth of PDAC and/or PSCs is unknown. Here we tested the hypothesis that mast cells contribute to the growth of PSCs and tumor cells, thus contributing to PDAC development. Tumor cells promoted mast cell migration. Both tumor cells and PSCs stimulated mast cell activation. Conversely, mast cell-derived IL-13 and tryptase stimulated PSC proliferation. Treating tumor-bearing mice with agents that block mast cell migration and function depressed PDAC growth. Our findings suggest that mast cells exacerbate the cellular and extracellular dynamics of the tumor microenvironment found in PDAC. Therefore, targeting mast cells may inhibit stromal formation and improve therapy. PMID:23633481

  3. Effect of selective T cell depletion of host and/or donor bone marrow on lymphopoietic repopulation, tolerance, and graft-vs-host disease in mixed allogeneic chimeras (B10 + B10. D2----B10)

    SciTech Connect

    Ildstad, S.T.; Wren, S.M.; Bluestone, J.A.; Barbieri, S.A.; Stephany, D.; Sachs, D.H.

    1986-01-01

    Reconstitution of lethally irradiated mice with a mixture of T cell-depleted syngeneic plus T cell-depleted allogeneic bone marrow (B10 + B10.D2----B10) leads to the induction of mixed lymphopoietic chimerism, excellent survivals, specific in vivo transplantation tolerance to subsequent donor strain skin grafts, and specific in vitro unresponsiveness to allogeneic donor lymphoid elements as assessed by mixed lymphocyte reaction (MLR) proliferative and cell-mediated lympholysis (CML) cytotoxicity assays. When B10 recipient mice received mixed marrow inocula in which the syngeneic component had not been T cell depleted, whether or not the allogeneic donor marrow was treated, they repopulated exclusively with host-type cells, promptly rejected donor-type skin allografts, and were reactive in vitro to the allogeneic donor by CML and MLR assays. In contrast, T cell depletion of the syngeneic component of the mixed marrow inocula resulted in specific acceptance of allogeneic donor strain skin grafts. Such animals were specifically unreactive to allogeneic donor lymphoid elements in vitro by CML and MLR, but were reactive to third party. When both the syngeneic and allogeneic marrow were T cell depleted, variable percentages of host- and donor-type lymphoid elements were detected in the mixed reconstituted host. When only the syngeneic bone marrow was T cell depleted, animals repopulated exclusively with donor-type cells. Although these animals had detectable in vitro anti-host (B10) reactivity by CML and MLR and reconstituted as fully allogeneic chimeras, they exhibited excellent survival and had no in vivo evidence for graft-vs-host disease. Experiments in which untreated donor spleen cells were added to the inocula in this last group suggest that the presence of T cell-depleted syngeneic bone marrow cells diminishes graft-vs-host disease and the mortality from it.

  4. Overview of physics results from MAST towards ITER/DEMO and the MAST Upgrade

    NASA Astrophysics Data System (ADS)

    Meyer, H.; Abel, I. G.; Akers, R. J.; Allan, A.; Allan, S. Y.; Appel, L. C.; Asunta, O.; Barnes, M.; Barratt, N. C.; Ben Ayed, N.; Bradley, J. W.; Canik, J.; Cahyna, P.; Cecconello, M.; Challis, C. D.; Chapman, I. T.; Ciric, D.; Colyer, G.; Conway, N. J.; Cox, M.; Crowley, B. J.; Cowley, S. C.; Cunningham, G.; Danilov, A.; Darke, A.; De Bock, M. F. M.; De Temmerman, G.; Dendy, R. O.; Denner, P.; Dickinson, D.; Dnestrovsky, A. Y.; Dnestrovsky, Y.; Driscoll, M. D.; Dudson, B.; Dunai, D.; Dunstan, M.; Dura, P.; Elmore, S.; Field, A. R.; Fishpool, G.; Freethy, S.; Fundamenski, W.; Garzotti, L.; Ghim, Y. C.; Gibson, K. J.; Gryaznevich, M. P.; Harrison, J.; Havlíčková, E.; Hawkes, N. C.; Heidbrink, W. W.; Hender, T. C.; Highcock, E.; Higgins, D.; Hill, P.; Hnat, B.; Hole, M. J.; Horáček, J.; Howell, D. F.; Imada, K.; Jones, O.; Kaveeva, E.; Keeling, D.; Kirk, A.; Kočan, M.; Lake, R. J.; Lehnen, M.; Leggate, H. J.; Liang, Y.; Lilley, M. K.; Lisgo, S. W.; Liu, Y. Q.; Lloyd, B.; Maddison, G. P.; Mailloux, J.; Martin, R.; McArdle, G. J.; McClements, K. G.; McMillan, B.; Michael, C.; Militello, F.; Molchanov, P.; Mordijck, S.; Morgan, T.; Morris, A. W.; Muir, D. G.; Nardon, E.; Naulin, V.; Naylor, G.; Nielsen, A. H.; O'Brien, M. R.; O'Gorman, T.; Pamela, S.; Parra, F. I.; Patel, A.; Pinches, S. D.; Price, M. N.; Roach, C. M.; Robinson, J. R.; Romanelli, M.; Rozhansky, V.; Saarelma, S.; Sangaroon, S.; Saveliev, A.; Scannell, R.; Seidl, J.; Sharapov, S. E.; Schekochihin, A. A.; Shevchenko, V.; Shibaev, S.; Stork, D.; Storrs, J.; Sykes, A.; Tallents, G. J.; Tamain, P.; Taylor, D.; Temple, D.; Thomas-Davies, N.; Thornton, A.; Turnyanskiy, M. R.; Valovič, M.; Vann, R. G. L.; Verwichte, E.; Voskoboynikov, P.; Voss, G.; Warder, S. E. V.; Wilson, H. R.; Wodniak, I.; Zoletnik, S.; Zagôrski, R.; MAST, the; NBI Teams

    2013-10-01

    New diagnostic, modelling and plant capability on the Mega Ampère Spherical Tokamak (MAST) have delivered important results in key areas for ITER/DEMO and the upcoming MAST Upgrade, a step towards future ST devices on the path to fusion currently under procurement. Micro-stability analysis of the pedestal highlights the potential roles of micro-tearing modes and kinetic ballooning modes for the pedestal formation. Mitigation of edge localized modes (ELM) using resonant magnetic perturbation has been demonstrated for toroidal mode numbers n = 3, 4, 6 with an ELM frequency increase by up to a factor of 9, compatible with pellet fuelling. The peak heat flux of mitigated and natural ELMs follows the same linear trend with ELM energy loss and the first ELM-resolved Ti measurements in the divertor region are shown. Measurements of flow shear and turbulence dynamics during L-H transitions show filaments erupting from the plasma edge whilst the full flow shear is still present. Off-axis neutral beam injection helps to strongly reduce the redistribution of fast-ions due to fishbone modes when compared to on-axis injection. Low-k ion-scale turbulence has been measured in L-mode and compared to global gyro-kinetic simulations. A statistical analysis of principal turbulence time scales shows them to be of comparable magnitude and reasonably correlated with turbulence decorrelation time. Te inside the island of a neoclassical tearing mode allow the analysis of the island evolution without assuming specific models for the heat flux. Other results include the discrepancy of the current profile evolution during the current ramp-up with solutions of the poloidal field diffusion equation, studies of the anomalous Doppler resonance compressional Alfvén eigenmodes, disruption mitigation studies and modelling of the new divertor design for MAST Upgrade. The novel 3D electron Bernstein synthetic imaging shows promising first data sensitive to the edge current profile and flows.

  5. Subthreshold IKK activation modulates the effector functions of primary mast cells and allows specific targeting of transformed mast cells

    PubMed Central

    Drube, Sebastian; Beyer, Mandy; Rothe, Mandy; Rabenhorst, Anja; Göpfert, Christiane; Meininger, Isabel; Diamanti, Michaela A.; Stegner, David; Häfner, Norman; Böttcher, Martin; Reinecke, Kirstin; Herdegen, Thomas; Greten, Florian R.; Nieswandt, Bernhard; Hartmann, Karin; Krämer, Oliver H.; Kamradt, Thomas

    2015-01-01

    Mast cell differentiation and proliferation depends on IL-3. IL-3 induces the activation of MAP-kinases and STATs and consequently induces proliferation and survival. Dysregulation of IL-3 signaling pathways also contribute to inflammation and tumorigenesis. We show here that IL-3 induces a SFK- and Ca2+-dependent activation of the inhibitor of κB kinases 2 (IKK2) which results in mast cell proliferation and survival but does not induce IκBα-degradation and NFκB activation. Therefore we propose the term “subthreshold IKK activation”. This subthreshold IKK activation also primes mast cells for enhanced responsiveness to IL-33R signaling. Consequently, co-stimulation with IL-3 and IL-33 increases IKK activation and massively enhances cytokine production induced by IL-33. We further reveal that in neoplastic mast cells expressing constitutively active Ras, subthreshold IKK activation is associated with uncontrolled proliferation. Consequently, pharmacological IKK inhibition reduces tumor growth selectively by inducing apoptosis in vivo. Together, subthreshold IKK activation is crucial to mediate the full IL-33-induced effector functions in primary mast cells and to mediate uncontrolled proliferation of neoplastic mast cells. Thus, IKK2 is a new molecularly defined target structure. PMID:25749030

  6. Subthreshold IKK activation modulates the effector functions of primary mast cells and allows specific targeting of transformed mast cells.

    PubMed

    Drube, Sebastian; Weber, Franziska; Loschinski, Romy; Beyer, Mandy; Rothe, Mandy; Rabenhorst, Anja; Göpfert, Christiane; Meininger, Isabel; Diamanti, Michaela A; Stegner, David; Häfner, Norman; Böttcher, Martin; Reinecke, Kirstin; Herdegen, Thomas; Greten, Florian R; Nieswandt, Bernhard; Hartmann, Karin; Krämer, Oliver H; Kamradt, Thomas

    2015-03-10

    Mast cell differentiation and proliferation depends on IL-3. IL-3 induces the activation of MAP-kinases and STATs and consequently induces proliferation and survival. Dysregulation of IL-3 signaling pathways also contribute to inflammation and tumorigenesis. We show here that IL-3 induces a SFK- and Ca²⁺-dependent activation of the inhibitor of κB kinases 2 (IKK2) which results in mast cell proliferation and survival but does not induce IκBα-degradation and NFκB activation. Therefore we propose the term "subthreshold IKK activation".This subthreshold IKK activation also primes mast cells for enhanced responsiveness to IL-33R signaling. Consequently, co-stimulation with IL-3 and IL-33 increases IKK activation and massively enhances cytokine production induced by IL-33.We further reveal that in neoplastic mast cells expressing constitutively active Ras, subthreshold IKK activation is associated with uncontrolled proliferation. Consequently, pharmacological IKK inhibition reduces tumor growth selectively by inducing apoptosis in vivo.Together, subthreshold IKK activation is crucial to mediate the full IL-33-induced effector functions in primary mast cells and to mediate uncontrolled proliferation of neoplastic mast cells. Thus, IKK2 is a new molecularly defined target structure. PMID:25749030

  7. Does the mast cell have an intrinsic role in the pathogenesis of interstitial cystitis?

    PubMed

    Frenz, A M; Christmas, T J; Pearce, F L

    1994-06-01

    In order to examine the role of mast cells in the inflammatory bladder disease interstitial cystitis, mast cells isolated from the human bladder of normal and diseased tissue were challenged with a range of secretagogues. Calcium ionophore A23187 and anti-IgE caused histamine release from all bladder mast cells in a dose-related manner. Mast cells from the diseased tissue were far more responsive than those from the normal tissue. Mast cells from the muscle of normal bladder were responsive towards substance P and compound 48/80. However, mast cells from interstitial cystitis bladder did not release significant amounts of histamine with these two secretagogues.

  8. Mast cells mediate malignant pleural effusion formation

    PubMed Central

    Giannou, Anastasios D.; Marazioti, Antonia; Spella, Magda; Kanellakis, Nikolaos I.; Apostolopoulou, Hara; Psallidas, Ioannis; Prijovich, Zeljko M.; Vreka, Malamati; Zazara, Dimitra E.; Lilis, Ioannis; Papaleonidopoulos, Vassilios; Kairi, Chrysoula A.; Patmanidi, Alexandra L.; Giopanou, Ioanna; Spiropoulou, Nikolitsa; Harokopos, Vaggelis; Aidinis, Vassilis; Spyratos, Dionisios; Teliousi, Stamatia; Papadaki, Helen; Taraviras, Stavros; Snyder, Linda A.; Eickelberg, Oliver; Kardamakis, Dimitrios; Iwakura, Yoichiro; Feyerabend, Thorsten B.; Rodewald, Hans-Reimer; Kalomenidis, Ioannis; Blackwell, Timothy S.; Agalioti, Theodora; Stathopoulos, Georgios T.

    2015-01-01

    Mast cells (MCs) have been identified in various tumors; however, the role of these cells in tumorigenesis remains controversial. Here, we quantified MCs in human and murine malignant pleural effusions (MPEs) and evaluated the fate and function of these cells in MPE development. Evaluation of murine MPE-competent lung and colon adenocarcinomas revealed that these tumors actively attract and subsequently degranulate MCs in the pleural space by elaborating CCL2 and osteopontin. MCs were required for effusion development, as MPEs did not form in mice lacking MCs, and pleural infusion of MCs with MPE-incompetent cells promoted MPE formation. Once homed to the pleural space, MCs released tryptase AB1 and IL-1β, which in turn induced pleural vasculature leakiness and triggered NF-κB activation in pleural tumor cells, thereby fostering pleural fluid accumulation and tumor growth. Evaluation of human effusions revealed that MCs are elevated in MPEs compared with benign effusions. Moreover, MC abundance correlated with MPE formation in a human cancer cell–induced effusion model. Treatment of mice with the c-KIT inhibitor imatinib mesylate limited effusion precipitation by mouse and human adenocarcinoma cells. Together, the results of this study indicate that MCs are required for MPE formation and suggest that MC-dependent effusion formation is therapeutically addressable. PMID:25915587

  9. Blockade of mast cell activation reduces cutaneous scar formation.

    PubMed

    Chen, Lin; Schrementi, Megan E; Ranzer, Matthew J; Wilgus, Traci A; DiPietro, Luisa A

    2014-01-01

    Damage to the skin initiates a cascade of well-orchestrated events that ultimately leads to repair of the wound. The inflammatory response is key to wound healing both through preventing infection and stimulating proliferation and remodeling of the skin. Mast cells within the tissue are one of the first immune cells to respond to trauma, and upon activation they release pro-inflammatory molecules to initiate recruitment of leukocytes and promote a vascular response in the tissue. Additionally, mast cells stimulate collagen synthesis by dermal fibroblasts, suggesting they may also influence scar formation. To examine the contribution of mast cells in tissue repair, we determined the effects the mast cell inhibitor, disodium cromoglycate (DSCG), on several parameters of dermal repair including, inflammation, re-epithelialization, collagen fiber organization, collagen ultrastructure, scar width and wound breaking strength. Mice treated with DSCG had significantly reduced levels of the inflammatory cytokines IL-1α, IL-1β, and CXCL1. Although DSCG treatment reduced the production of inflammatory mediators, the rate of re-epithelialization was not affected. Compared to control, inhibition of mast cell activity caused a significant decrease in scar width along with accelerated collagen re-organization. Despite the reduced scar width, DSCG treatment did not affect the breaking strength of the healed tissue. Tryptase β1 exclusively produced by mast cells was found to increase significantly in the course of wound healing. However, DSCG treatment did not change its level in the wounds. These results indicate that blockade of mast cell activation reduces scar formation and inflammation without further weakening the healed wound.

  10. The Role of TRP Proteins in Mast Cells

    PubMed Central

    Freichel, Marc; Almering, Julia; Tsvilovskyy, Volodymyr

    2012-01-01

    Transient receptor potential (TRP) proteins form cation channels that are regulated through strikingly diverse mechanisms including multiple cell surface receptors, changes in temperature, in pH and osmolarity, in cytosolic free Ca2+ concentration ([Ca2+]i), and by phosphoinositides which makes them polymodal sensors for fine tuning of many cellular and systemic processes in the body. The 28 TRP proteins identified in mammals are classified into six subfamilies: TRPC, TRPV, TRPM, TRPA, TRPML, and TRPP. When activated, they contribute to cell depolarization and Ca2+ entry. In mast cells, the increase of [Ca2+]i is fundamental for their biological activity, and several entry pathways for Ca2+ and other cations were described including Ca2+ release activated Ca2+ (CRAC) channels. Like in other non-excitable cells, TRP channels could directly contribute to Ca2+ influx via the plasma membrane as constituents of Ca2+ conducting channel complexes or indirectly by shifting the membrane potential and regulation of the driving force for Ca2+ entry through independent Ca2+ entry channels. Here, we summarize the current knowledge about the expression of individual Trp genes with the majority of the 28 members being yet identified in different mast cell models, and we highlight mechanisms how they can regulate mast cell functions. Since specific agonists or blockers are still lacking for most members of the TRP family, studies to unravel their function and activation mode still rely on experiments using genetic approaches and transgenic animals. RNAi approaches suggest a functional role for TRPC1, TRPC5, and TRPM7 in mast cell derived cell lines or primary mast cells, and studies using Trp gene knock-out mice reveal a critical role for TRPM4 in mast cell activation and for mast cell mediated cutaneous anaphylaxis, whereas a direct role of cold- and menthol-activated TRPM8 channels seems to be unlikely for the development of cold urticaria at least in mice. PMID:22701456

  11. Mast Cell Chemotaxis – Chemoattractants and Signaling Pathways

    PubMed Central

    Halova, Ivana; Draberova, Lubica; Draber, Petr

    2012-01-01

    Migration of mast cells is essential for their recruitment within target tissues where they play an important role in innate and adaptive immune responses. These processes rely on the ability of mast cells to recognize appropriate chemotactic stimuli and react to them by a chemotactic response. Another level of intercellular communication is attained by production of chemoattractants by activated mast cells, which results in accumulation of mast cells and other hematopoietic cells at the sites of inflammation. Mast cells express numerous surface receptors for various ligands with properties of potent chemoattractants. They include the stem cell factor (SCF) recognized by c-Kit, antigen, which binds to immunoglobulin E (IgE) anchored to the high affinity IgE receptor (FcεRI), highly cytokinergic (HC) IgE recognized by FcεRI, lipid mediator sphingosine-1-phosphate (S1P), which binds to G protein-coupled receptors (GPCRs). Other large groups of chemoattractants are eicosanoids [prostaglandin E2 and D2, leukotriene (LT) B4, LTD4, and LTC4, and others] and chemokines (CC, CXC, C, and CX3C), which also bind to various GPCRs. Further noteworthy chemoattractants are isoforms of transforming growth factor (TGF) β1–3, which are sensitively recognized by TGF-β serine/threonine type I and II β receptors, adenosine, C1q, C3a, and C5a components of the complement, 5-hydroxytryptamine, neuroendocrine peptide catestatin, tumor necrosis factor-α, and others. Here we discuss the major types of chemoattractants recognized by mast cells, their target receptors, as well as signaling pathways they utilize. We also briefly deal with methods used for studies of mast cell chemotaxis and with ways of how these studies profited from the results obtained in other cellular systems. PMID:22654878

  12. Intestinal and peritoneal mast cells differ in kinetics of quantal release.

    PubMed

    Balseiro-Gomez, Santiago; Ramirez-Ponce, M Pilar; Acosta, Jorge; Ales, Eva; Flores, Juan A

    2016-01-15

    5-hydroxytriptamine (5-HT, serotonin) storage and release in mast cell (MC) secretory granules (SG) are dependent on serglycin proteoglycans (PG). This notion is based on the studies of MC of the connective tissue subtype that predominantly contain PG of the heparin type, whereas intestinal mucosal MC, which contain predominantly chondroitin sulfate, have been poorly explored. In the present study, we addressed the possibility that PG contents may differently affect the storage and release of preformed mediators in these two MC subclasses and explain in part their different functional properties. Rat peritoneal (PMC) and intestinal mast cells (IMC) were isolated and purified using a percoll gradient, and the efflux of 5-HT from each SG was measured by amperometric detection. IMC exhibited a ∼34% reduction in the release of 5-HT compared with PMC because of a lower number of exocytotic events, rather than a lower secretion per single exocytotic event. Amperometric spikes from IMC exhibited a slower decay phase and increased half-width but a similar ascending phase and foot parameters, indicating that the fusion pore kinetics are comparable in both MC subclasses. We conclude that both PG subtypes are equally efficient systems, directly involved in serotonin accumulation, and play a crucial role in regulating the kinetics of exocytosis from SG, providing specific secretory properties for the two cellular subtypes. PMID:26692491

  13. Cultures of mast cell-like (MCL) cells from human pleural exudate cells.

    PubMed

    Krüger, G; Sterry, W; Czarnetzki, B M

    1983-03-01

    Under special culture conditions, rat peritoneal macrophages have previously been shown to transform into mast cells. This method has been adapted here to the human species. Adherent large mononuclear cells from human pleural exudates were cultured in a medium supplemented with horse serum (30%) and fibroblast supernatants (30%). Metachromatic staining (toluidine blue, pH 3.6) of cytoplasmic granules appeared first in a small percentage of cells by days 5-6 of culture and reached a high intensity in 50% of the cells between days 12-22. Histamine levels within the cells increased by a factor of 7 during this same time period and the cell size by a factor of 3. Cultures could be maintained for about three weeks, since viability and total cell number decreased on extended culture. The data suggest that mononuclear cells in inflammatory exudates can transform into mast cell-like cells under the influence of high levels of specific conditioning factors in their microenvironment. PMID:6824794

  14. Intestinal and peritoneal mast cells differ in kinetics of quantal release.

    PubMed

    Balseiro-Gomez, Santiago; Ramirez-Ponce, M Pilar; Acosta, Jorge; Ales, Eva; Flores, Juan A

    2016-01-15

    5-hydroxytriptamine (5-HT, serotonin) storage and release in mast cell (MC) secretory granules (SG) are dependent on serglycin proteoglycans (PG). This notion is based on the studies of MC of the connective tissue subtype that predominantly contain PG of the heparin type, whereas intestinal mucosal MC, which contain predominantly chondroitin sulfate, have been poorly explored. In the present study, we addressed the possibility that PG contents may differently affect the storage and release of preformed mediators in these two MC subclasses and explain in part their different functional properties. Rat peritoneal (PMC) and intestinal mast cells (IMC) were isolated and purified using a percoll gradient, and the efflux of 5-HT from each SG was measured by amperometric detection. IMC exhibited a ∼34% reduction in the release of 5-HT compared with PMC because of a lower number of exocytotic events, rather than a lower secretion per single exocytotic event. Amperometric spikes from IMC exhibited a slower decay phase and increased half-width but a similar ascending phase and foot parameters, indicating that the fusion pore kinetics are comparable in both MC subclasses. We conclude that both PG subtypes are equally efficient systems, directly involved in serotonin accumulation, and play a crucial role in regulating the kinetics of exocytosis from SG, providing specific secretory properties for the two cellular subtypes.

  15. Approaches for Analyzing the Roles of Mast Cells and Their Proteases In Vivo

    PubMed Central

    Galli, Stephen J.; Tsai, Mindy; Marichal, Thomas; Tchougounova, Elena; Reber, Laurent L.; Pejler, Gunnar

    2016-01-01

    The roles of mast cells in health and disease remain incompletely understood. While the evidence that mast cells are critical effector cells in IgE-dependent anaphylaxis and other acute IgE-mediated allergic reactions seems unassailable, studies employing various mice deficient in mast cells or mast cell-associated proteases have yielded divergent conclusions about the roles of mast cells or their proteases in certain other immunological responses. Such “controversial” results call into question the relative utility of various older versus newer approaches to ascertain the roles of mast cells and mast cell proteases in vivo. This review discusses how both older and more recent mouse models have been used to investigate the functions of mast cells and their proteases in health and disease. We particularly focus on settings in which divergent conclusions about the importance of mast cells and their proteases have been supported by studies that employed different models of mast cell or mast cell protease deficiency. We think that two major conclusions can be drawn from such findings: (1) no matter which models of mast cell or mast cell protease deficiency one employs, the conclusions drawn from the experiments always should take into account the potential limitations of the models (particularly abnormalities affecting cell types other than mast cells) and (2) even when analyzing a biological response using a single model of mast cell or mast cell protease deficiency, details of experimental design are critical in efforts to define those conditions under which important contributions of mast cells or their proteases can be identified. PMID:25727288

  16. Imaging immune response of skin mast cells in vivo with two-photon microscopy

    NASA Astrophysics Data System (ADS)

    Li, Chunqiang; Pastila, Riikka K.; Lin, Charles P.

    2012-02-01

    Intravital multiphoton microscopy has provided insightful information of the dynamic process of immune cells in vivo. However, the use of exogenous labeling agents limits its applications. There is no method to perform functional imaging of mast cells, a population of innate tissue-resident immune cells. Mast cells are widely recognized as the effector cells in allergy. Recently their roles as immunoregulatory cells in certain innate and adaptive immune responses are being actively investigated. Here we report in vivo mouse skin mast cells imaging with two-photon microscopy using endogenous tryptophan as the fluorophore. We studied the following processes. 1) Mast cells degranulation, the first step in the mast cell activation process in which the granules are released into peripheral tissue to trigger downstream reactions. 2) Mast cell reconstitution, a procedure commonly used to study mast cells functioning by comparing the data from wild type mice, mast cell-deficient mice, and mast-cell deficient mice reconstituted with bone marrow-derived mast cells (BMMCs). Imaging the BMMCs engraftment in tissue reveals the mast cells development and the efficiency of BMMCs reconstitution. We observed the reconstitution process for 6 weeks in the ear skin of mast cell-deficient Kit wsh/ w-sh mice by two-photon imaging. Our finding is the first instance of imaging mast cells in vivo with endogenous contrast.

  17. Mast cell-cholinergic nerve interaction in mouse airways.

    PubMed

    Weigand, Letitia A; Myers, Allen C; Meeker, Sonya; Undem, Bradley J

    2009-07-01

    We addressed the mechanism by which antigen contracts trachea isolated from actively sensitized mice. Trachea were isolated from mice (C57BL/6J) that had been actively sensitized to ovalbumin (OVA). OVA (10 microg ml(-1)) caused histamine release (approximately total tissue content), and smooth muscle contraction that was rapid in onset and short-lived (t(1/2) < 1 min), reaching approximately 25% of the maximum tissue response. OVA contraction was mimicked by 5-HT, and responses to both OVA and 5-HT were sensitive to 10 microm-ketanserin (5-HT(2) receptor antagonist) and strongly inhibited by atropine (1microm). Epithelial denudation had no effect on the OVA-induced contraction. Histological assessment revealed about five mast cells/tracheal section the vast majority of which contained 5-HT. There were virtually no mast cells in the mast cell-deficient (sash -/-) mouse trachea. OVA failed to elicit histamine release or contractile responses in trachea isolated from sensitized mast cell-deficient (sash -/-) mice. Intracellular recordings of the membrane potential of parasympathetic neurons in mouse tracheal ganglia revealed a ketanserin-sensitive 5-HT-induced depolarization and similar depolarization in response to OVA challenge. These data support the hypothesis that antigen-induced contraction of mouse trachea is epithelium-independent, and requires mast cell-derived 5-HT to activate 5-HT(2) receptors on parasympathetic cholinergic neurons. This leads to acetylcholine release from nerve terminals, and airway smooth muscle contraction. PMID:19403609

  18. The transcription factor Zeb2 regulates signaling in mast cells.

    PubMed

    Barbu, Emilia Alina; Zhang, Juan; Berenstein, Elsa H; Groves, Jacqueline R; Parks, Lauren M; Siraganian, Reuben P

    2012-06-15

    Mast cell activation results in the release of stored and newly synthesized inflammatory mediators. We found that Zeb2 (also named Sip1, Zfhx1b), a zinc finger transcription factor, regulates both early and late mast cell responses. Transfection with small interfering RNA (siRNA) reduced Zeb2 expression and resulted in decreased FcεRI-mediated degranulation, with a parallel reduction in receptor-induced activation of NFAT and NF-κB transcription factors, but an enhanced response to the LPS-mediated activation of NF-κB. There was variable and less of a decrease in the Ag-mediated release of the cytokines TNF-α, IL-13, and CCL-4. This suggests that low Zeb2 expression differentially regulates signaling pathways in mast cells. Multiple phosphorylation events were impaired that affected molecules both at early and late events in the signaling pathway. The Zeb2 siRNA-treated mast cells had altered cell cycle progression, as well as decreased expression of several molecules including cell surface FcεRI and its β subunit, Gab2, phospholipase-Cγ1, and phospholipase-Cγ2, all of which are required for receptor-induced signal transduction. The results indicate that the transcription factor Zeb2 controls the expression of molecules thereby regulating signaling in mast cells.

  19. Mast Cells as Cellular Sensors in Inflammation and Immunity

    PubMed Central

    Beghdadi, Walid; Madjene, Lydia Célia; Benhamou, Marc; Charles, Nicolas; Gautier, Gregory; Launay, Pierre; Blank, Ulrich

    2011-01-01

    Mast cells are localized in tissues. Intense research on these cells over the years has demonstrated their role as effector cells in the maintenance of tissue integrity following injury produced by infectious agents, toxins, metabolic states, etc. After stimulation they release a sophisticated array of inflammatory mediators, cytokines, and growth factors to orchestrate an inflammatory response. These mediators can directly initiate tissue responses on resident cells, but they have also been shown to regulate other infiltrating immune cell functions. Research in recent years has revealed that the outcome of mast cell actions is not always detrimental for the host but can also limit disease development. In addition, mast cell functions highly depend on the physiological context in the organism. Depending on the genetic background, strength of the injurious event, the particular microenvironment, mast cells direct responses ranging from pro- to anti-inflammatory. It appears that they have evolved as cellular sensors to discern their environment in order to initiate an appropriate physiological response either aimed to favor inflammation for repair or at the contrary limit the inflammatory process to prevent further damage. Like every sophisticated machinery, its dysregulation leads to pathology. Given the broad distribution of mast cells in tissues this also explains their implication in many inflammatory diseases. PMID:22566827

  20. Mast cell heterogeneity in non-human primates

    SciTech Connect

    Barrett, K.E.; Szucs, E.F.; Metcalfe, D.D.

    1986-03-05

    Mast cells of rodents may be subdivided in terms of their properties, but the extent of such heterogeneity in man and higher animals is still unknown. The authors have compared lung (LMC) and intestinal (IMC) mast cells obtained from individual monkeys. LMC contained more histamine (HA) than IMC (6.61+/-1.3 vs. 1.6+/-0.6 pg/cell, means+/-SEM, n=3). LMC released more HA (17.7+/-2.1% vs. 9.2+/-1.0%, means+/-SEM, n=16) and also generated more LTC/sub 4/ equivalents as measured by radioimmunoassay (range 13.4-41.5 vs. 3.0-4.0 ng/10/sup 6/ mast cells) following an anaphylactic stimulus. The majority (>90%) of LMC stained metachromatically under conditions appropriate for heparin-containing cells, whereas IMC required more forcing conditions to display metachromasia. In contrast to these quantitative and qualitative mediator differences, functional responses of LMC and IMC were similar. Thus, HA release was inhibited comparably by theophylline, isoprenaline and dibutyryl cyclic AMP, but quercetin was slightly more active on IMC. Substance P caused dose-related HA release from both cell types, although the amount released varied between individual animal, (range LMC 1.2-20.2%, IMC 1.8-23.0%, n=4). Other neuropeptides (pentagastrin) vasoactive intestinal peptide, neurotensin, somatostatin) did not release HA. They conclude that mast cell heterogeneity in higher animals may be reflected more by cytochemical rather than functional differences between mast cell classes.

  1. Impaired CD4 T Cell Memory Response to Streptococcus pneumoniae Precedes CD4 T Cell Depletion in HIV-Infected Malawian Adults

    PubMed Central

    Mzinza, David; Harawa, Visopo; Miles, David J. C.; Jambo, Kondwani C.; Gordon, Stephen B.; Williams, Neil A.; Heyderman, Robert S.

    2011-01-01

    Objective Invasive pneumococcal disease (IPD) is a leading cause of morbidity and mortality in HIV-infected African adults. CD4 T cell depletion may partially explain this high disease burden but those with relatively preserved T cell numbers are still at increased risk of IPD. This study evaluated the extent of pneumococcal-specific T cell memory dysfunction in asymptomatic HIV infection early on in the evolution of the disease. Methods Peripheral blood mononuclear cells were isolated from asymptomatic HIV-infected and HIV-uninfected Malawian adults and stained to characterize the underlying degree of CD4 T cell immune activation, senescence and regulation. Pneumococcal-specific T cell proliferation, IFN-γ, IL-17 production and CD154 expression was assessed using flow cytometry and ELISpot. Results We find that in asymptomatic HIV-infected Malawian adults, there is considerable immune disruption with an increase in activated and senescent CD4+CD38+PD-1+ and CD4+CD25highFoxp3+ Treg cells. In the context of high pneumococcal exposure and therefore immune stimulation, show a failure in pneumococcal-specific memory T cell proliferation, skewing of T cell cytokine production with preservation of interleukin-17 but decreased interferon-gamma responses, and failure of activated T cells to express the co-stimulatory molecule CD154. Conclusion Asymptomatic HIV-infected Malawian adults show early signs of pneumococcal- specific immune dysregulation with a shift in the balance of CD4 memory, T helper 17 cells and Treg. Together these data offer a mechanistic understanding of how antigen-specific T cell dysfunction occurs prior to T cell depletion and may explain the early susceptibility to IPD in those with relatively preserved CD4 T cell numbers. PMID:21980502

  2. Expression profiling of constitutive mast cells reveals a unique identity within the immune system

    PubMed Central

    Dwyer, Daniel F.; Barrett, Nora A.; Austen, K. Frank

    2016-01-01

    Mast cells are evolutionarily ancient sentinel cells. Like basophils, mast cells express the high-affinity IgE receptor and are implicated in host defense and diverse immune-mediated diseases. To better characterize the function of these cells, we assessed the transcriptional profiles of mast cells isolated from peripheral connective tissues and basophils isolated from spleen and blood. We found that mast cells were transcriptionally distinct, clustering independently from all other profiled cells, and that mast cells demonstrated considerably greater heterogeneity across tissues than previously appreciated. We observed minimal homology between mast cells and basophils, which share more overlap with other circulating granulocytes than with mast cells. Derivation of mast cell and basophil transcriptional signatures underscores their differential capacity to detect environmental signals and influence the inflammatory milieu. PMID:27135604

  3. Principles of treatment for mast cell tumors.

    PubMed

    Govier, Susanne M

    2003-05-01

    Mast cell tumors (MCT) are the most common malignant cutaneous tumors that occur in dogs. They are most commonly found on the trunk, accounting for approximately 50% to 60% of all sites. MCTs associated with the limbs account for approximately 25% of all sites. Cutaneous MCTs have a wide variety of clinical appearances. Histologic grade is the most consistent prognostic factor available for dogs. MCTs located at 'nail bed' (subungual), inguinal/preputial area, and any mucocutaneous area like perineum or oral cavity carry a guarded prognosis and tend to metastasize. MCTs usually exfoliate well and are cytologically distinct. The extent of staging procedures following fine-needle aspirate cytologic diagnosis is based on the presence or absence of negative prognostic indicators. Surgery is the treatment of choice for solitary MCTs with no evidence of metastasis. Reponses rates to chemotherapy, (partial response) as high as 78% have been reported, and preliminary evidence suggests that multiagent (prednisone and vinblastine) protocols may confer a higher response rate than single-agent therapy. MCTs are the second most common cutaneous tumor in the cat. There are two distinct forms of cutaneous MCTs in the cat. The more common form is the mastocytic form, and the less common is the histiocytic form. Unlike in the dog, the head and neck are the most common sites for MCTs in the cat followed by the trunk and limbs. Cats with disseminated forms of MCT often present with systemic signs of illness, which include depression, anorexia, weight loss, and vomiting. The diagnosis and staging of MCTs in cats is similar to that in the dog. As with dogs with cutaneous MCTs, surgery is the treatment of choice. Little is known about the effectiveness of adjunctive chemotherapy options for cutaneous MCTs. Adjunctive chemotherapy does not appear to increase survival times.

  4. Dual view FIDA measurements on MAST

    NASA Astrophysics Data System (ADS)

    Michael, C. A.; Conway, N.; Crowley, B.; Jones, O.; Heidbrink, W. W.; Pinches, S.; Braeken, E.; Akers, R.; Challis, C.; Turnyanskiy, M.; Patel, A.; Muir, D.; Gaffka, R.; Bailey, S.

    2013-09-01

    A fast-ion deuterium alpha (FIDA) spectrometer was installed on MAST to measure radially resolved information about the fast-ion density and its distribution in energy and pitch angle. Toroidally and vertically directed collection lenses are employed, to detect both passing and trapped particle dynamics, and reference views are installed to subtract the background. This background is found to contain a substantial amount of passive FIDA emission driven by edge neutrals, and to depend delicately on viewing geometry. Results are compared with theoretical expectations based on the codes NUBEAM (for fast-ion distributions) and FIDASIM. Calibrating via the measured beam emission peaks, the toroidal FIDA signal profile agrees with classical simulations in magnetohydrodynamic quiescent discharges where the neutron rate is also classical. Long-lived modes (LLMs) and chirping modes decrease the core FIDA signal significantly, and the profile can be matched closely to simulations using anomalous diffusive transport; a spatially uniform diffusion coefficient is sufficient for chirping modes, while a core localized diffusion is better for a LLM. Analysis of a discharge with chirping mode activity shows a dramatic drop in the core FIDA signal and rapid increase in the edge passive signal at the onset of the burst indicating a very rapid redistribution towards the edge. Vertical-viewing measurements show a discrepancy with simulations at higher Doppler shifts when the neutron rate is classical, which, combined with the fact that the toroidal signals agree, means that the difference must be occurring for pitch angles near the trapped-passing boundary, although uncertainties in the background subtraction, which are difficult to assess, may contribute to this. Further evidence of an anomalous transport mechanism for these particles is provided by the fact that an increase of beam power does not increase the higher energy vertical FIDA signals, while the toroidal signals do increase.

  5. Inhibitory effects of BiRyuChe-bang on mast cell-mediated allergic reactions and inflammatory cytokines production.

    PubMed

    Moon, Phil-Dong; Choi, Il Sang; Go, Ji-Hyun; Lee, Byong-Joo; Kang, Sang Woo; Yoon, Sunhee; Han, Seung-Jun; Nam, Sun-Young; Oh, Hyun-A; Han, Na-Ra; Kim, Young-Sick; Kim, Ju-Sung; Kim, Myong-Jo; Jeong, Hyun-Ja; Kim, Hyung-Min

    2013-01-01

    BiRyuChe-bang (BRC) is a Korean prescription medicine, which has been used to treat allergic rhinitis at Kyung Hee Medical Center. In this work, we investigated the effects of BRC on mast cell-mediated allergic reactions and inflammatory cytokines production, and identified the active component of BRC. Histamine release was measured from rat peritoneal mast cells (RPMCs). Ear swelling and passive cutaneous anaphylaxis (PCA) were examined in mouse models. Phorbol 12-myristate 13-acetate (PMA) plus A23187-induced inflammatory cytokines production was measured using enzyme-linked immunosorbent assay. Reverse transcriptase-polymerase chain reaction was used for the expressions of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-8. Activation of nuclear factor (NF)-κB was analyzed by Western blotting. BRC significantly inhibited the compound 48/80-induced ear swelling response, histamine release from RPMCs, PCA activated by anti-dinitrophenyl IgE, and PMA plus A23187-induced inflammatory cytokines production (p < 0.05). In addition, BRC dose-dependently inhibited the mRNA expressions of TNF-α, IL-6, and IL-8 as well as the activation of NF-κB in a human mast cell line, HMC-1 cells. BRC inhibited the levels of TNF-α and IL-6 in mice induced with PCA. Several components of BRC, such as 1,8-Cineole, Linalool, Linalyl acetate, α-Pinene, and α-Terpineol, significantly inhibited the release of histamine from RPMCs (p < 0.05). Among these components, Linalyl acetate was the most effective for inhibiting histamine release. These results indicate that BRC has a potential regulatory effect on allergic and inflammatory reactions mediated by mast cells.

  6. Effects of seed abundance on seed scatter-hoarding of Edward's rat (Leopoldamys edwardsi Muridae) at the individual level.

    PubMed

    Zhang, Hongmao; Cheng, Jinrui; Xiao, Zhishu; Zhang, Zhibin

    2008-11-01

    Mast seeding is a common phenomenon, and has important effects on seed dispersal and hoarding by animals. At population level, the predator satiation hypothesis proposes that the satiating effect of a large amount of seeds on a relatively small number of predators benefits seed survival in mast-seeding years. However, the effect of mast seeding on the scatter-hoarding of rodents at the individual level is largely unknown. In this study, we investigated the effects of seed abundance (by simulating mast seeding and non-mast seeding) on the removal, consumption and scatter-hoarding of seeds of Camellia oleifera (Theaceae) by Edward's rat Leopoldamys edwardsi (Muridae) in seminatural enclosures in southwest China. We wanted to test the masting-enhanced hoarding hypothesis, which suggests that rodents tend to scatter-hoard more seeds in mast-seeding years in order to occupy more food resources. Our results indicate that L. edwardsi tended to disperse and scatter-hoard more seeds of C. oleifera per night with increasing seed abundance, and to eat less seeds per night when there was a high level of seed abundance in the enclosure experiments. These results support the masting-enhanced hoarding hypothesis. This capacity of rodents may be an evolutionary adaptation to the mast-seeding phenomenon. Our results suggest that mast seeding benefits forest regeneration not only through the predator satiation effect at the population level, but also through increased hoarding by animals at the individual level.

  7. The role of mast cell in tissue morphogenesis. Thymus, duodenum, and mammary gland as examples.

    PubMed

    Ribatti, Domenico; Crivellato, Enrico

    2016-02-01

    Mast cells (MCs) are strategically located at host/environment interfaces like skin, airways, and gastro-intestinal and uro-genital tracts. MCs also populate connective tissues in association with blood and lymphatic vessels and nerves. MCs are absent in avascular tissues, such as mineralized bone, cartilage, and cornea. MCs have various functions and different functional subsets of MCs are encountered in different tissues. However, we do not' know exactly what is the physiological function of MC. Most of these functions are not essential for life, as various MC-deficient strains of mice and rats seems to have normal life spans. In this review article, we have reported and discussed the literature data concerning the role of MCs in tissue morphogenesis, and in particular their role in the development of thymus, duodenum, and mammary gland. PMID:26615957

  8. Capillary electrophoretic study of individual exocytotic events in single mast cells

    SciTech Connect

    Ho, A.M.W.

    1999-02-12

    The peak profile of individual degranulation events from the on-column release of serotonin from single rat peritoneal mast cells (RPMCs) was monitored using capillary electrophoresis with laser-induced native fluorescence detection (CE-LINF). Serotonin, an important biogenic amine, is contained in granules (0.25 fL) within RPMCs and is extruded by a process termed exocytosis. The secretagogue, Polymyxin B sulfate, was used as the CE running buffer after injection of a single RPMC into the separation capillary to stimulate the release of the granules. Because the release process occurs on a ms time scale, monitoring individual exocytotic events is possible with the coupling of high-speed CE and LINF detection.

  9. The role of mast cell in tissue morphogenesis. Thymus, duodenum, and mammary gland as examples.

    PubMed

    Ribatti, Domenico; Crivellato, Enrico

    2016-02-01

    Mast cells (MCs) are strategically located at host/environment interfaces like skin, airways, and gastro-intestinal and uro-genital tracts. MCs also populate connective tissues in association with blood and lymphatic vessels and nerves. MCs are absent in avascular tissues, such as mineralized bone, cartilage, and cornea. MCs have various functions and different functional subsets of MCs are encountered in different tissues. However, we do not' know exactly what is the physiological function of MC. Most of these functions are not essential for life, as various MC-deficient strains of mice and rats seems to have normal life spans. In this review article, we have reported and discussed the literature data concerning the role of MCs in tissue morphogenesis, and in particular their role in the development of thymus, duodenum, and mammary gland.

  10. Mast cells mediate acute inflammatory responses to implanted biomaterials

    PubMed Central

    Tang, Liping; Jennings, Timothy A.; Eaton, John W.

    1998-01-01

    Implanted biomaterials trigger acute and chronic inflammatory responses. The mechanisms involved in such acute inflammatory responses can be arbitrarily divided into phagocyte transmigration, chemotaxis, and adhesion to implant surfaces. We earlier observed that two chemokines—macrophage inflammatory protein 1α/monocyte chemoattractant protein 1—and the phagocyte integrin Mac-1 (CD11b/CD18)/surface fibrinogen interaction are, respectively, required for phagocyte chemotaxis and adherence to biomaterial surfaces. However, it is still not clear how the initial transmigration of phagocytes through the endothelial barrier into the area of the implant is triggered. Because implanted biomaterials elicit histaminic responses in the surrounding tissue, and histamine release is known to promote rapid diapedesis of inflammatory cells, we evaluated the possible role of histamine and mast cells in the recruitment of phagocytes to biomaterial implants. Using i.p. and s.c. implantation of polyethylene terephthalate disks in mice we find: (i) Extensive degranulation of mast cells, accompanied by histamine release, occurs adjacent to short-term i.p. implants. (ii) Simultaneous administration of H1 and H2 histamine receptor antagonists (pyrilamine and famotidine, respectively) greatly diminishes recruitment and adhesion of both neutrophils (<20% of control) and monocytes/macrophages (<30% of control) to implants. (iii) Congenitally mast cell-deficient mice also exhibit markedly reduced accumulation of phagocytes on both i.p. and s.c implants. (iv) Finally, mast cell reconstitution of mast cell-deficient mice restores “normal” inflammatory responses to biomaterial implants. We conclude that mast cells and their granular products, especially histamine, are important in recruitment of inflammatory cells to biomaterial implants. Improved knowledge of such responses may permit purposeful modulation of both acute and chronic inflammation affecting implanted biomaterials. PMID

  11. 30 CFR 56.7051 - Loose objects on the mast or drill platform.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Loose objects on the mast or drill platform. 56... Drilling and Rotary Jet Piercing Drilling § 56.7051 Loose objects on the mast or drill platform. To prevent injury to personnel, tools and other objects shall not be left loose on the mast or drill platform....

  12. 30 CFR 56.7051 - Loose objects on the mast or drill platform.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Loose objects on the mast or drill platform. 56... Drilling and Rotary Jet Piercing Drilling § 56.7051 Loose objects on the mast or drill platform. To prevent injury to personnel, tools and other objects shall not be left loose on the mast or drill platform....

  13. Mast cells: Versatile regulators of inflammation, tissue remodeling, host defense and homeostasis

    PubMed Central

    Galli, Stephen J.; Tsai, Mindy

    2009-01-01

    Summary The possible roles of mast cells in heath and disease have been a topic of interest for over one hundred and twenty five years. Many adaptive or pathological processes affecting the skin or other anatomical sites have been associated with morphological evidence of mast cell activation, and/or with changes in mast cell numbers or phenotype. Such observations, taken together with the known functions of the diverse mediators, cytokines and growth factors which can be secreted by mast cells, have suggested many potential functions for mast cells in health and disease. Definitively identifying the importance of mast cells in biological responses in humans is difficult. However, mutant mice which are profoundly mast cell-deficient, especially those which can undergo engraftment with wild type or genetically-altered mast cells, provide an opportunity to investigate the importance of mast cells, and specific mast cell functions or products, in various adaptive or pathological responses in mice. Such work has shown that mast cells can significantly influence multiple features of inflammatory or immune responses, through diverse effects that can either promote or, surprisingly, suppress, aspects of these responses. Through such functions, mast cells can significantly influence inflammation, tissue remodeling, host defense and homeostasis. PMID:18024086

  14. 30 CFR 77.807-2 - Booms and masts; minimum distance from high-voltage lines.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... WORK AREAS OF UNDERGROUND COAL MINES Surface High-Voltage Distribution § 77.807-2 Booms and masts; minimum distance from high-voltage lines. The booms and masts of equipment operated on the surface of any... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Booms and masts; minimum distance from...

  15. 30 CFR 77.807-2 - Booms and masts; minimum distance from high-voltage lines.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... WORK AREAS OF UNDERGROUND COAL MINES Surface High-Voltage Distribution § 77.807-2 Booms and masts; minimum distance from high-voltage lines. The booms and masts of equipment operated on the surface of any... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Booms and masts; minimum distance from...

  16. 30 CFR 77.807-2 - Booms and masts; minimum distance from high-voltage lines.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... WORK AREAS OF UNDERGROUND COAL MINES Surface High-Voltage Distribution § 77.807-2 Booms and masts; minimum distance from high-voltage lines. The booms and masts of equipment operated on the surface of any... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Booms and masts; minimum distance from...

  17. 30 CFR 77.807-2 - Booms and masts; minimum distance from high-voltage lines.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... WORK AREAS OF UNDERGROUND COAL MINES Surface High-Voltage Distribution § 77.807-2 Booms and masts; minimum distance from high-voltage lines. The booms and masts of equipment operated on the surface of any... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Booms and masts; minimum distance from...

  18. Structure and biological activities of eumenine mastoparan-AF (EMP-AF), a new mast cell degranulating peptide in the venom of the solitary wasp (Anterhynchium flavomarginatum micado).

    PubMed

    Konno, K; Hisada, M; Naoki, H; Itagaki, Y; Kawai, N; Miwa, A; Yasuhara, T; Morimoto, Y; Nakata, Y

    2000-11-01

    A new mast cell degranulating peptide, eumenine mastoparan-AF (EMP-AF), was isolated from the venom of the solitary wasp Anterhynchium flavomarginatum micado, the most common eumenine wasp found in Japan. The structure was analyzed by FAB-MS/MS together with Edman degradation, which was corroborated by solid-phase synthesis. The sequence of EMP-AF, Ile-Asn-Leu-Leu-Lys-Ile-Ala-Lys-Gly-Ile-Ile-Lys-Ser-Leu-NH(2), was similar to that of mastoparan, a mast cell degranulating peptide from a hornet venom; tetradecapeptide with C-terminus amidated and rich in hydrophobic and basic amino acids. In fact, EMP-AF exhibited similar activity to mastoparan in stimulating degranulation from rat peritoneal mast cells and RBL-2H3 cells. It also showed significant hemolytic activity in human erythrocytes. Therefore, this is the first example that a mast cell degranulating peptide is found in the solitary wasp venom. Besides the degranulation and hemolytic activity, EMP-AF also affects on neuromuscular transmission in the lobster walking leg preparation. Three analogs EMP-AF-1 approximately 3 were snythesized and biologically tested together with EMP-AF, resulting in the importance of the C-terminal amide structure for biological activities.

  19. Estrogen inhibits mast cell chymase release to prevent pressure overload-induced adverse cardiac remodeling.

    PubMed

    Li, Jianping; Jubair, Shaiban; Janicki, Joseph S

    2015-02-01

    Estrogen regulation of myocardial chymase and chymase effects on cardiac remodeling are unknown. To test the hypothesis that estrogen prevents pressure overload-induced adverse cardiac remodeling by inhibiting mast cell (MC) chymase release, transverse aortic constriction or sham surgery was performed in 7-week-old intact and ovariectomized (OVX) rats. Three days before creating the constriction, additional groups of OVX rats began receiving 17β-estradiol, a chymase inhibitor, or a MC stabilizer. Left ventricular function, cardiomyocyte size, collagen volume fraction, MC density and degranulation, and myocardial and plasma chymase levels were assessed 18 days postsurgery. Aortic constriction resulted in ventricular hypertrophy in intact and OVX groups, whereas collagen volume fraction was increased only in OVX rats. Chymase protein content was increased by aortic constriction in the intact and OVX groups, with the magnitude of the increase being greater in OVX rats. MC density and degranulation, plasma chymase levels, and myocardial active transforming growth factor-β1 levels were increased by aortic constriction only in OVX rats. Estrogen replacement markedly attenuated the constriction-increased myocardial chymase, MC density and degranulation, plasma chymase, and myocardial active transforming growth factor-β1, as well as prevented ventricular hypertrophy and increased collagen volume fraction. Chymostatin attenuated the aortic constriction-induced ventricular hypertrophy and collagen volume fraction in the OVX rats similar to that achieved by estrogen replacement. Nedocromil yielded similar effects, except for the reduction of chymase content. We conclude that the estrogen-inhibited release of MC chymase is responsible for the cardioprotection against transverse aortic constriction-induced adverse cardiac remodeling.

  20. Passive cutaneous anaphylaxis in the rat, induced with two homologous reagin-like antibodies, and its specific inhibition with disodium cromoglycate

    PubMed Central

    Goose, J.; Blair, A. M. J. N.

    1969-01-01

    Rats immunized with egg albumin and Bordetella pertussis organisms produce a `mast cell sensitizing' antibody (MCSAb) which is thermolabile, a potent skin sensitizer and reagin in character. Similarly the immune response to Nippostrongylus brasiliensis in rats is closely associated with the formation of antibodies which also resembles human reagins. Homologous passive cutaneous anaphylactic (PCA) reactions induced by N. brasiliensis serum were found to be similar to those produced using the adjuvant induced antibody in that both were completely inhibited by, combined treatment with mepyramine and 2-bromo-D-lysergic acid diethylamide (BOL148), cyproheptadine or pretreatment with compound 48/80. In contrast, skin reactions involving passive sensitization of rats with rabbit hyperimmune antiserum were much less affected. Studies on mast cell disruption at the site of PCA reactions showed that such reactions using N. brasiliensis serum were accompanied by degranulation of mast cells, and confirmed that mast cell damage occurs in PCA induced with MCSAb. Both the PCA and the mast cell disruption were maximal 5 minutes after antigen challenge in both rat reagin systems. The skin reaction produced using rabbit hyperimmune antiserum was not primarily dependent on, or associated with, mast cell disruption, since it was still possible to induce skin reactions when the mast cells had been disrupted by compound 48/80, and skin reactions could be obtained without significant mast cell disruption. Disodium cromoglycate, a new compound introduced for the treatment of asthma, was shown to inhibit both the PCA and mast cell disruption induced using both rat reagin antibodies but not the skin reactions produced with rabbit anti-serum. It was possible to obtain substantial inhibition of mast cell disruption induced by rat reagin, even when the PCA was inhibited only slightly. At higher doses the discharge of the mediators from mast cells was also prevented. This interference with mast

  1. The mast cells of the mammalian central nervous system. VI. Uptake of tritiated thymidine by mast cells, neurolipomastocytoid cells and other elements of the central nervous system.

    PubMed

    Ibrahim, M Z; Koshayan, D S; Khreis, Y M

    1980-01-01

    The central nervous system (CNS) of two mammalian species was studied autoradiographically using tritium-labeled thymidine; the rat, whose brain contains few localized mast cells (MCs) but many ubiquitous neurolipomastocytoid cells (NLMs), and the guinea pig, whose brain contains only ubiquitous NLMs. A few guinea pigs were also injected with an MC discharger compound 48/80 and the response of the NLMs, which are thought to be allied to MCs, as well as of neuroglial and vascular endothelial cells, was noted. The rats were 3 days to 6 weeks old whereas all the guinea pigs were young adults. Both MCs and NLMs took up the label, and much more so in the babies, paralleling similar uptakes in only very small immature MCs outside the CNS. Neuroglial elements, especially subependymal and oligodendroglial, as well as endothelial, perivascular, leptomeningeal and ependymal cells demonstrated some uptake. This was considerably increased upon receipt of compound 48/80, especially in the case of the subependymal glia, the NLMs and the endothelial cells; capillary neoformations were seen in the spinal cords of guinea pigs that had shown signs of paralysis. The cause of this increase is discussed in terms of mild stress induced by that compound. The subependymal response is also discussed with reference to periventricular plaques seen in multiple sclerosis and lymphoreticular and glial tumors seen in that region. It is concluded that both MCs and NLMs are capable of DNA replication and mitosis in immature animals. The NLMs can also divide upon stimulation in adult CNS.

  2. Mast cells mediate the immune suppression induced by dermal exposure to JP-8 jet fuel.

    PubMed

    Limón-Flores, Alberto Y; Chacón-Salinas, Rommel; Ramos, Gerardo; Ullrich, Stephen E

    2009-11-01

    Applying jet propulsion-8 (JP-8) jet fuel to the skin of mice induces immune suppression. Applying JP-8 to the skin of mice suppresses T-cell-mediated immune reactions including, contact hypersensitivity (CHS) delayed-type hypersensitivity and T-cell proliferation. Because dermal mast cells play an important immune regulatory role in vivo, we tested the hypothesis that mast cells mediate jet fuel-induced immune suppression. When we applied JP-8 to the skin of mast cell deficient mice CHS was not suppressed. Reconstituting mast cell deficient mice with wild-type bone marrow derived mast cells (mast cell "knock-in mice") restored JP-8-induced immune suppression. When, however, mast cells from prostaglandin E(2) (PGE(2))-deficient mice were used, the ability of JP-8 to suppress CHS was not restored, indicating that mast cell-derived PGE(2) was activating immune suppression. Examining the density of mast cells in the skin and lymph nodes of JP-8-treated mice indicated that jet fuel treatment caused an initial increase in mast cell density in the skin, followed by increased numbers of mast cells in the subcutaneous space and then in draining lymph nodes. Applying JP-8 to the skin increased mast cell expression of CXCR4, and increased the expression of CXCL12 by draining lymph node cells. Because CXCL12 is a chemoattractant for CXCR4+ mast cells, we treated JP-8-treated mice with AMD3100, a CXCR4 antagonist. AMD3100 blocked the mobilization of mast cells to the draining lymph node and inhibited JP-8-induced immune suppression. Our findings demonstrate the importance of mast cells in mediating jet fuel-induced immune suppression.

  3. B cell depletion with rituximab in patients with rheumatoid arthritis: Multiplex bead array reveals the kinetics of IgG and IgA antibodies to citrullinated antigens.

    PubMed

    Cambridge, Geraldine; Leandro, Maria J; Lahey, Lauren J; Fairhead, Thomas; Robinson, William H; Sokolove, Jeremy

    2016-06-01

    The serology of patients with Rheumatoid arthritis (RA) is characterized by persistently raised levels of autoantibodies: Rheumatoid Factors (RhF) against Fc of IgG, and to citrullinated (Cit) protein/peptide sequences: ACPA, recognizing multiple Cit-sequences. B cell depletion therapy based on rituximab delivers good clinical responses in RA patients, particularly in the seropositive group, with responses sometimes lasting beyond the phase of B cell reconstitution. In general, ACPA levels fall following rituximab, but fluctuations with respect to predicting relapse have proved disappointing. In order to identify possible immunodominant specificities within either IgG- or IgA-ACPA we used a Multiplex bead-based array consisting of 30 Cit-peptides/proteins and 22 corresponding native sequences. The kinetics of the serum ACPA response to individual specificities was measured at key points (Baseline, B cell depletion phase, Relapse) within an initial cycle of rituximab therapy in 16 consecutive patients with severe, active RA. All had achieved significant decreases in Disease Activity Scores-28 and maintained B cell depletion in the peripheral blood (<5 CD19+cells/μl) for at least 3 months. At Baseline, mean fluorescence intensity shown by individual IgG- and IgA-ACPA were strongly correlated (R(2) = 0.75; p < 0.0001) but IgA-ACPA were approximately 10-fold lower. Data were Z-normalised in order to compare serial results and antibody classes. At Baseline, a total of 68 IgG- and 51 IgA-ACPA had Z-scores ≥ 1 (above population mean) were identified, with at least one Cit-antigen identified in each serum. ACPA to individual specificities subsequently fluctuated with 3 different patterns. Most 51/68 (75%) IgG- and 48/51 IgA-ACPA (94%) fell between Baseline and Depletion, of which 57% IgG- and 65% IgA-ACPA rebounded pre-Relapse. Interestingly, 17/68 IgG-ACPA (25%) and some IgA-ACPA (3/51; 6%) transiently increased from Baseline, subsequently falling pre

  4. High-throughput charge exchange recombination spectroscopy system on MAST

    SciTech Connect

    Conway, N. J.; Carolan, P. G.; McCone, J.; Walsh, M. J.; Wisse, M.

    2006-10-15

    A major upgrade to the charge exchange recombination spectroscopy system on MAST has recently been implemented. The new system consists of a high-throughput spectrometer coupled to a total of 224 spatial channels, including toroidal and poloidal views of both neutral heating beams on MAST. Radial resolution is {approx}1 cm, comparable to the ion Larmor radius. The toroidal views are configured with 64 channels per beam, while the poloidal views have 32 channels per beam. Background channels for both poloidal and toroidal views are also provided. A large transmission grating is at the heart of the new spectrometer, with high quality single lens reflex lenses providing excellent imaging performance and permitting the full exploitation of the available etendue of the camera sensor. The charge-coupled device camera chosen has four-tap readout at a maximum aggregate speed of 8.8 MHz, and it is capable of reading out the full set of 224 channels in less than 4 ms. The system normally operates at 529 nm, viewing the C{sup 5+} emission line, but can operate at any wavelength in the range of 400-700 nm. Results from operating the system on MAST are shown, including impurity ion temperature and velocity profiles. The system's excellent spatial resolution is ideal for the study of transport barrier phenomena on MAST, an activity which has already been advanced significantly by data from the new diagnostic.

  5. Diagnosis and treatment of mast cell disorders: practical recommendations.

    PubMed

    Sandes, Alex Freire; Medeiros, Raphael Salles Scortegagna; Rizzatti, Edgar Gil

    2013-01-01

    CONTEXT AND OBJECTIVE The term mastocytosis covers a group of rare disorders characterized by neoplastic proliferation and accumulation of clonal mast cells in one or more organs. The aim of this study was to assess the principal elements for diagnosing and treating these disorders. DESIGN AND SETTING Narrative review of the literature conducted at Grupo Fleury, São Paulo, Brazil. METHODS This study reviewed the scientific papers published in the PubMed, Embase (Excerpta Medica Database), Lilacs (Literatura Latino-Americana e do Caribe em Ciências da Saúde) and Cochrane Library databases that were identified using the search term "mastocytosis." RESULTS The clinical presentation of mastocytosis is remarkably heterogeneous and ranges from skin lesions that may regress spontaneously to aggressive forms associated with organ failure and short survival. Currently, seven subtypes of mastocytosis are recognized through the World Health Organization classification system for hematopoietic tumors. These disorders are diagnosed based on clinical manifestations and on identification of neoplastic mast cells using morphological, immunophenotypic, genetic and molecular methods. Abnormal mast cells display atypical and frequently spindle-shaped morphology, and aberrant expression of the CD25 and CD2 antigens. Elevation of serum tryptase is a common finding in some subtypes, and more than 90% of the patients present the D816V KIT mutation in mast cells. CONCLUSION Here, we described the most common signs and symptoms among patients with mastocytosis and suggested a practical approach for the diagnosis, classification and initial clinical treatment of mastocytosis.

  6. Design of deployable-truss masts for Space Station

    NASA Technical Reports Server (NTRS)

    Bowden, Mary; Benton, Max

    1993-01-01

    This paper presents an overview of three deployable-truss designs that were considered for use on Space Station Freedom to deploy the solar array wings. The first design chosen early in the program was a nut-deployed coilable longeron mast which has the advantage of being lightweight and reliable, with considerable flight history. Subsequently, because of the restructure of Space Station, a second design was chosen: a lanyard-deployed FASTMast (Folding Articulated Square Truss Mast), which has improved strength and redundancy characteristics for a given stowed volume. After further definition of the load requirements during deployment, however, it became necessary to modify the deployment system, resulting in the third mast design for space station solar arrays: a nut-deployed FASTMast, which was ultimately selected to provide increased stiffness and strength during deployment. This paper presents a brief review of these mast designs and their associated deployment systems, emphasizing the trade-offs involved in selecting between them. In addition, some innovative features of the FASTMast design as it stands currently for Space Station are described, and a brief review of the test program that is underway to qualify this design for flight is included.

  7. Clonal mast cell activation syndrome with anaphylaxis to sulfites.

    PubMed

    Cifuentes, Liliana; Ring, Johannes; Brockow, Knut

    2013-01-01

    Sulfites are rarely suspected as causative agents of immediate-type hypersensitivity. We report on a 49-year-old male patient who developed recurrent severe hypotension after food ingestion. A diagnosis of monoclonal mast cell activation syndrome was established. In the double-blind, placebo-controlled food challenge, the patient reacted to potassium metabisulfite with anaphylaxis.

  8. Mast Cell Targeted Chimeric Toxin Can Be Developed as an Adjunctive Therapy in Colon Cancer Treatment

    PubMed Central

    Wang, Shan; Li, Linmei; Shi, Renren; Liu, Xueting; Zhang, Junyan; Zou, Zehong; Hao, Zhuofang; Tao, Ailin

    2016-01-01

    The association of colitis with colorectal cancer has become increasingly clear with mast cells being identified as important inflammatory cells in the process. In view of the relationship between mast cells and cancer, we studied the effect and mechanisms of mast cells in the development of colon cancer. Functional and mechanistic insights were gained from ex vivo and in vivo studies of cell interactions between mast cells and CT26 cells. Further evidence was reversely obtained in studies of mast cell targeted Fcε-PE40 chimeric toxin. Experiments revealed mast cells could induce colon tumor cell proliferation and invasion. Cancer progression was found to be related to the density of mast cells in colonic submucosa. The activation of MAPK, Rho-GTPase, and STAT pathways in colon cancer cells was triggered by mast cells during cell-to-cell interaction. Lastly, using an Fcε-PE40 chimeric toxin we constructed, we confirmed the promoting effect of mast cells in development of colon cancer. Mast cells are a promoting factor of colon cancer and thus also a potential therapeutic target. The Fcε-PE40 chimeric toxin targeting mast cells could effectively prevent colon cancer in vitro and in vivo. Consequently, these data may demonstrate a novel immunotherapeutic approach for the treatment of tumors. PMID:26978404

  9. Masting promotes individual- and population-level reproduction by increasing pollination efficiency.

    PubMed

    Moreira, Xoaquín; Abdala-Roberts, Luis; Linhart, Yan B; Mooney, Kailen A

    2014-04-01

    Masting is a reproductive strategy defined as the intermittent and synchronized production of large seed crops by a plant population. The pollination efficiency hypothesis proposes that masting increases pollination success in plants. Despite its general appeal, no previous studies have used long-term data together with population- and individual-level analyses to assess pollination efficiency between mast and non-mast events. Here we rigorously tested the pollination efficiency hypothesis in ponderosa pine (Pinus ponderosa), a long-lived monoecious, wind-pollinated species, using a data set on 217 trees monitored annually for 20 years. Relative investment in male and female function by individual trees did not vary between mast and non-mast years. At both the population and individual level, the rate of production of mature female cones relative to male strobili production was higher in mast than non-mast years, consistent with the predicted benefit of reproductive synchrony on reproductive success. In addition, at the individual level we found a higher conversion of unfertilized female conelets into mature female cones during a mast year compared to a non-mast year. Collectively, parallel results at the population and individual tree level provide robust evidence for the ecological, and potentially also evolutionary, benefits of masting through increased pollination efficiency.

  10. Coevolution of mast seeding in trees and extended diapause of seed predators.

    PubMed

    Tachiki, Yuuya; Iwasa, Yoh

    2013-12-21

    Many trees in forests show synchronized and intermittent reproduction, which is called "masting" or mast seeding. According to recent theoretical studies, the evolution of masting is promoted both by recruitment through the seedling bank and by seed predators. An important class of specialist seed predators (e.g., weevils and some moths) are parasitoids that oviposit on or in fruits from which the next generation emerges over the following several years. This staggered emergence is called "extended diapause". In this paper, we study the simultaneous evolution of tree masting and extended diapause of seed predators. If a fixed fraction of diapausing larvae matures every year, the evolution of trees results in masting (intermittent reproduction with a large fluctuation in reproductive activity) or non-masting (trees reproduce every year). The transition occurs discontinuously, showing evolutionary jumping. The range of seedling survivorship for which masting evolves is broader when the ovipositing efficiency and larval survivorship of the seed predators are large. Interestingly, the conditions for the evolution of masting are broadest for an intermediate fraction of extended diapause of seed predators. When both tree masting and the extended diapause of seed predators evolve simultaneously, the evolutionary end point of the fraction of extended diapause is clearly greater than the value that most favors masting evolution. The stochasticity caused by the finiteness of the number of trees tends to promote masting evolution.

  11. New Kepler Data Products At MAST For Stellar Astrophysics

    NASA Astrophysics Data System (ADS)

    Fleming, Scott W.; Shiao, B.; Tseng, S.; Million, C.; Thompson, R.; Seibert, M.; Abney, F.; Donaldson, T.; Dower, T.; Fraquelli, D. A.; Handy, S.; Koekemoer, A. M.; Levay, K.; Matuskey, J.; McLean, B.; Quick, L.; Rogers, A.; Wallace, G.; White, R. L.

    2014-01-01

    The Kepler Mission has collected high-precision, time-series photometry of over 200,000 stars. The reduced lightcurves, target pixel files, and a variety of catalog metadata are already available at MAST. We present new data products and services at MAST that will further aid researchers as Kepler begins its transition to a legacy mission, particularly in the realm of stellar astrophysics. New photometric catalogs to accompany the Kepler targets have arrived at MAST within the past year, and several more will be coming in the relative future. These include the second half of the Kepler INT survey (U,g,r,i,H_alpha; available now), an improved GALEX source catalog (NUV and FUV; available now), PanSTARRS (g,r,i,z; available soon), and WISE (3.4, 4.6, 12, and 22 microns; planned). We expect searches for variability will become one of the most active areas of archive use, so MAST is including a wide range of variability statistics as part of the archive database. In addition to being searchable through database queries and web forms, each Preview page will now include a summary of these variability indices for each of the target's lightcurves within a Quarter. Along with updated NUV and FUV fluxes, a new tool at MAST called gPhoton will allow users to create time-series lightcurves, including animated movies and intensity images, from any set of GALEX photons with arbitrary aperture and bin sizes. We show some examples of the ways GALEX UV lightcurves generated with gPhoton can be used in conjunction with the Kepler data. Finally, MAST has released an initial version of its Data Discovery Portal. This one-stop, interactive web application gives users the ability to search and access data from any of MAST's missions (HST, GALEX, Kepler, FUSE, IUE, JWST, etc.), as well as any data available through the Virtual Observatory. It includes filtering options, access to interactive displays, an accompanying AstroViewer with data footprints on-sky, the ability to upload your own

  12. Cutaneous mast cell tumor (Mastocytoma): Cyto- histopathological and haematological investigations

    PubMed Central

    2014-01-01

    Cutaneous mast cell tumours (MCTs) are the most common skin tumours in dogs. Due to the prevalence of canine MCTs and the variable biologic behavior of this disease, accurate prognostication and a thorough understanding of MCT biology are critical for the treatment of this disease. A cytologic diagnosis of mast cell tumor with evidence of prior hemorrhage was made, and the masses were surgically removed. Cytological evaluation of fine-needle aspirates from the cutaneous mass from the axillary comprised many well-differentiated, highly granulated mast cells with moderate numbers of eosinophils. Nuclei were varied in size and shape with high nuclear’to’cytoplasmic ratio, prominent nucleoli, marked atypical and mitotic figures. Microscopically, mass consisted of sheets of neoplastic round cells that formed nonencapsulated nodules in the dermis and infiltrated into the adjacent dermal collagen, and also there was diffuse subcutis invasion of round to pleomorphic tumor cells. Tumor cells had moderate to abundant cytoplasm, round to ovoid nuclei with scattered chromatin, and mitotic figures. In this tumor, cytoplasmic granules showed atypical metachromasia. In addition, eosinophils were scattered among the mast cells at the periphery of the nodules. The presence of eosinophils and the observation, at high magnification, of cells with cytoplasmic metachromatic granules. Invasion of the deep subcutaneous fat or cutaneous muscles were a common feature of grade III tumour. Finally, a diagnosis of grade III cutaneous mast cell tumor was made. Virtual slides The virtual slide(s) of this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/4755249151157024. PMID:24444100

  13. Mast cell-derived tryptase in odontogenic cysts.

    PubMed

    Teronen, O; Hietanen, J; Lindqvist, C; Salo, T; Sorsa, T; Eklund, K K; Sommerhoff, C P; Ylipaavalniemi, P; Konttinen, Y T

    1996-08-01

    Inflammatory and developmental cysts of the jaws are relatively common bone destructive lesions in the human maxillofacial skeleton but their pathogenesis is still poorly understood. In this study the role of mast cells (MC), and mast cell tryptase in particular, was evaluated in the pathophysiology of bone resorption and jaw cyst formation in different types of cysts. The distribution of MC and the amount of tryptase in histological tissue sections were determined by immunohistochemistry using monoclonal antihuman tryptase antibodies and the results were quantitated by using an image analyzing system. The amount of tryptase was further studied by Western-blotting and measurement of trypsin-like activity from the neutral salt extracts obtained from different types of jaw cysts. In contrast to control tissue, high trypsin-like activities and abundant immunoreactive tryptase were observed in the extracts of all types of cysts studied (radicular, dentigerous and keratocyst). In tissue sections the highest amount of tryptase-positive staining was observed in radicular cysts (mean 6.2% of reference area) and the lowest amount in keratocysts (mean 2.1% of reference area, P < 0.01). MC were found to be located in inflammatory cell-rich tissue areas and just beneath the cyst epithelium. Importantly, MC located at the border of bone were observed to be degranulated, indicating high activity of MC and release of tryptase at the regions of early bone destruction. Based on previous findings addressing the role of mast cell tryptase in proteolytic cascades, and the known association of MC with osteoporosis, we suggest that mast cells and mast cell tryptase may contribute significantly to jaw cyst tissue remodelling during growth of a cyst, and to the destruction of the surrounding bone, resulting in jaw cyst expansion.

  14. High viral burden and rapid CD4+ cell depletion in human immunodeficiency virus type 1-infected SCID-hu mice suggest direct viral killing of thymocytes in vivo.

    PubMed Central

    Jamieson, B D; Uittenbogaart, C H; Schmid, I; Zack, J A

    1997-01-01

    The mechanism of CD4+ cell loss in lymphoid organs is unknown. In this study, human immunodeficiency virus (HIV) infection of human fetal thymus/liver implants in severe combined immunodeficient mice was used to investigate the mechanism of HIV-induced depletion of CD4-bearing cells in vivo. The implants were assessed for depletion of CD4+ thymocytes, apoptosis, and viral burden. We detected two phases of CD4 cell depletion, an initial rapid phase and a more gradual later phase. Compared to mock-infected implants, HIV-infected implants did not demonstrate detectable increases in the levels of apoptosis while severe depletion of CD4-bearing cells was ongoing. During peak loss of CD4+ cells, high viral burden was observed, suggesting that loss of CD4+ cells in this in vivo system is due to direct killing of infected thymocytes. Increased levels of apoptosis were observed during the later phase of thymocyte depletion; however, these apoptotic cells lacked CD4. This finding suggests that a second indirect mechanism may be responsible for the destruction of CD4- CD8+ thymocytes in vivo. Taken together, these results suggest that CD4+ and CD4- cells may die by different mechanism(s). PMID:9343176

  15. Pegylated G-CSF Inhibits Blood Cell Depletion, Increases Platelets, Blocks Splenomegaly, and Improves Survival after Whole-Body Ionizing Irradiation but Not after Irradiation Combined with Burn

    PubMed Central

    Kiang, Juliann G.; Zhai, Min; Liao, Pei-Jyun; Bolduc, David L.; Elliott, Thomas B.; Gorbunov, Nikolai V.

    2014-01-01

    Exposure to ionizing radiation alone (radiation injury, RI) or combined with traumatic tissue injury (radiation combined injury, CI) is a crucial life-threatening factor in nuclear and radiological accidents. As demonstrated in animal models, CI results in greater mortality than RI. In our laboratory, we found that B6D2F1/J female mice exposed to 60Co-γ-photon radiation followed by 15% total-body-surface-area skin burns experienced an increment of 18% higher mortality over a 30-day observation period compared to irradiation alone; that was accompanied by severe cytopenia, thrombopenia, erythropenia, and anemia. At the 30th day after injury, neutrophils, lymphocytes, and platelets still remained very low in surviving RI and CI mice. In contrast, their RBC, hemoglobin, and hematocrit were similar to basal levels. Comparing CI and RI mice, only RI induced splenomegaly. Both RI and CI resulted in bone marrow cell depletion. It was observed that only the RI mice treated with pegylated G-CSF after RI resulted in 100% survival over the 30-day period, and pegylated G-CSF mitigated RI-induced body-weight loss and depletion of WBC and platelets. Peg-G-CSF treatment sustained RBC balance, hemoglobin levels, and hematocrits and inhibited splenomegaly after RI. The results suggest that pegylated G-CSF effectively sustained animal survival by mitigating radiation-induced cytopenia, thrombopenia, erythropenia, and anemia. PMID:24738019

  16. Virus infection-associated bone marrow B cell depletion and impairment of humoral immunity to heterologous infection mediated by TNF-alpha/LTalpha.

    PubMed

    Borrow, Persephone; Hou, Sam; Gloster, Simone; Ashton, Miranda; Hyland, Lisa

    2005-02-01

    We previously showed that influenza virus infection of mice induces a depletion of bone marrow B lineage cells due to apoptosis of early B cells mediated by a mechanism involving TNF-alpha/LTalpha. Here we demonstrate that this effect is also observed with acute lymphocytic choriomeningitis virus (LCMV) infection and resulted in a deficiency of both splenic transitional B cells and mature follicular B cells. To determine whether there was an associated impairment of humoral immunity, we infected mice with LCMV and 10 days later at the peak of the B cell depletion, inoculated them with influenza virus. We found that influenza virus-specific antibody titers were dramatically reduced in mice recovering from LCMV infection compared to those in mice infected with influenza virus alone. Further, we showed that there was no reduction of the influenza virus-specific antibody response in LCMV-infected TNF-alpha/LTalpha-deficient mice, suggesting that TNF-alpha/LTalpha-mediated effects on bone marrow and/or peripheral lymphocytes were responsible for the observed impairment in humoral immunity. These results show that the TNF-alpha/LTalpha production induced following infection with diverse viruses has detrimental effects on early B cells in the bone marrow, and may be among the factors that lead to the severely compromised humoral immunity observed to subsequent heterologous infections. PMID:15657949

  17. Regulatory T-cell depletion in the gut caused by integrin β7 deficiency exacerbates DSS colitis by evoking aberrant innate immunity.

    PubMed

    Zhang, H L; Zheng, Y J; Pan, Y D; Xie, C; Sun, H; Zhang, Y H; Yuan, M Y; Song, B L; Chen, J F

    2016-03-01

    Integrin α4β7 controls lymphocyte trafficking into the gut and has essential roles in inflammatory bowel disease (IBD). The α4β7-blocking antibody vedolizumab is approved for IBD treatment; however, high dose of vedolizumab aggravates colitis in a small percentage of patients. Herein, we show that integrin β7 deficiency results in colonic regulatory T (Treg) cell depletion and exacerbates dextran sulfate sodium (DSS) colitis by evoking aberrant innate immunity. In DSS-treated β7-deficient mice, the loss of colonic Treg cells induces excessive macrophage infiltration in the colon via upregulation of colonic epithelial intercellular adhesion molecule 1 and increases proinflammatory cytokine expression, thereby exacerbating DSS-induced colitis. Moreover, reconstitution of the colonic Treg cell population in β7-deficient mice suppresses aberrant innate immune response in the colon and attenuates DSS colitis. Thus, integrin α4β7 is essential for suppression of DSS colitis as it regulates the colonic Treg cell population and innate immunity.

  18. Human mast cells produce and release the cytotoxic lymphocyte associated protease granzyme B upon activation.

    PubMed

    Strik, Merel C M; de Koning, Pieter J A; Kleijmeer, Monique J; Bladergroen, Bellinda A; Wolbink, Angela M; Griffith, Janice M; Wouters, Dorine; Fukuoka, Yoshihiro; Schwartz, Lawrence B; Hack, C Erik; van Ham, S Marieke; Kummer, J Alain

    2007-07-01

    Mast cells are widely distributed throughout the body and express effector functions in allergic reactions, inflammatory diseases, and host defense. Activation of mast cells results in exocytosis of preformed chemical mediators and leads to novel synthesis and secretion of lipid mediators and cytokines. Here, we show that human mast cells also express and release the cytotoxic lymphocyte-associated protease, granzyme B. Granzyme B was active and localized in cytoplasmic granules, morphologically resembling those present in cytotoxic lymphocytes. Expression and release of granzyme B by mast cell-lines HMC-1 and LAD 2 and by cord blood- and mature skin-derived human mast cells depended on the mode of activation of these cells. In mast cell lines and cord blood-derived mast cells, granzyme B expression was mainly induced by non-physiological stimuli (A23187/PMA, Compound 48/80) and substance P. In contrast, mature skin-derived mast cells only produced granzyme B upon IgE-dependent stimulation. We conclude that granzyme B is expressed and released by human mast cells upon physiologic stimulation. This suggests a role for granzyme B as a novel mediator in mast cell biology.

  19. Quantitative evaluation of mast cells in cellularly dynamic and adynamic vascular malformations.

    PubMed

    Pasyk, K A; Cherry, G W; Grabb, W C; Sasaki, G H

    1984-01-01

    Mast cells were counted in 78 histologic specimens from 70 patients with various vascular malformations showing cellularly dynamic and cellularly adynamic lesions. In growing stages of strawberry hemangiomas, there was an increased number of mast cells (mean 11.0 cells per high-power field in stage III and 23.7 in stage IV), as well as a high number of mast cells in the initial involution of strawberry hemangiomas (stage V, mean 21.0 cells per high-power field). In later involuting stages (stages VI and VII), the number of mast cells decreased (mean 9.3 in stage VI; mean 4.7 in stage VII). In cellularly adynamic lesions, i.e., port wine stains, the mean number of mast cells was 4.8, and in congenital arteriovenous malformations, it was 3.6. In normal skin, the mean number of mast cells was 3.2. In cellular hemangiomas that showed active growth (stages III to IV), the number of mast cells was strikingly low (mean 1.3). It seems that the mast cells are not responsible for the proliferation of the endothelium or for growth of the hemangioma. The markedly increased number of mast cells in the growing stages and initial involuting stage of strawberry hemangiomas parallels the gradual growth of fibrous connective tissue inside the tumor. Mast cells may thus be a precursor of the beginning of the involution of a strawberry hemangioma. PMID:6691077

  20. Mast cell heparin stimulates migration of capillary endothelial cells in vitro

    PubMed Central

    1980-01-01

    Migration of capillary endothelial cells is an important component of angiogenesis in vivo. Increased numbers of mast cells have been associated with several types of angiogenesis. We have used a quantitative assay in vitro to demonstrate that mast cells release a factor that significantly increases bovine capillary endothelial cell migration. The factor is present in medium conditioned by mast cells as well as lysates of mast cells. The stimulatory effect of mast cells on migration is specific for capillary endothelial cells. Furthermore, mast cells have no mitogenic activity for capillary endothelial cells. Of all the secretory products of mast cells tested, only heparin stimulated capillary endothelial cell migration in vitro. Heparin preparations from a variety of sources stimulated capillary endothelial cell migration to the same degree but did not stimulate migration of several other cell types. The migration activity of heparin and mast cell conditioned medium was blocked by specific antagonists of heparin (protamine and heparinase), but not by chondroitinase ABC. The migration activity of mast cell conditioned medium was resistant to heat (100 degrees C) and incubation with proteolytic enzymes. These results suggest that the role of mast cells in angiogenesis may be to enhance migration of the endothelial cells of growing capillaries. PMID:7420025

  1. Quantitative observations on iliac bone marrow mast cells in chronic renal failure.

    PubMed Central

    Peart, K M; Ellis, H A

    1975-01-01

    Mast cells have been counted in sections of iliac bone from 61 control subjects at necropsy. Mast cells were found in all but three, and the range was 0-33-7, median 1-95 per mm2 marrow. The majority (82%) had less than 4-99 mast cells per mm2 marrow; in 37-7% there was less than 1 mast cell per mm2 marrow. In a group of 45 patients with chronic renal failure there was a significant increase in the numbers of mast cells (P less than 0-001) with a range of 0-96-55-63, median 9-55 per mm2 marrow. Mast cells were common in the areas of marrow fibrosis associated with osteitis fibrosa but this was not the sole cause of the increase since there was also an excess of mast cells in the non-fibrous parts of the marrow. There was a tendency towards greater numbers of mast cells in those cases with most marked osteitis fibrosa in association with the prominent marrow fibrosis, but there was no significant relationship between mast cell numbers and other features of oesteitis fibrosa such as the number of osteoclasts and the amount of woven bone formation. There was no relationship between the numbers of mast cells and the amounts of total bone, ostoid, percentage mineralization of cancellous bone, or the presence of osteomalacia. PMID:1206118

  2. Studies on the specific degranulation of mast cell sensitized by several allergens in vitro.

    PubMed

    Guo, Yongchao; Li, Zhenxing; Lin, Hong; Samee, Haider; Khalid, Jamil

    2009-04-01

    Food allergy is a major health issue worldwide. Mast cells play a very important role in the immediate hypersensitivity for which mast cell degranulation needs to be studied extensively. In this study, an approach was taken to study the characteristics of sensitized mast cell degranulation in vitro, which associated with the study of mast cells and animal models. BALB/c mice were immunized respectively by several food allergens, then blood and peritoneal mast cells were collected at different time points. A dynamic determination was carried out between mast cells and serumal IgE. Comparative analysis on sequential time points showed that there was a close coincidence between mast cell degranulation and IgE antibody titers in sensitized BALB/c mice. Furthermore, it is interesting that sensitized mast cells could implement specific degranulation against the challenges in vitro, but the closely tropomyosins induced mast cell degranulation displayed cross reactions. This is very similar to IgE resisting the allergens in vivo. The study disclosed some characteristics on mast cells, coming from sensitized BALB/c mice, degranulation in vitro.

  3. Nicotine inhibits Fc epsilon RI-induced cysteinyl leukotrienes and cytokine production without affecting mast cell degranulation through alpha 7/alpha 9/alpha 10-nicotinic receptors.

    PubMed

    Mishra, Neerad C; Rir-sima-ah, Jules; Boyd, R Thomas; Singh, Shashi P; Gundavarapu, Sravanthi; Langley, Raymond J; Razani-Boroujerdi, Seddigheh; Sopori, Mohan L

    2010-07-01

    Smokers are less likely to develop some inflammatory and allergic diseases. In Brown-Norway rats, nicotine inhibits several parameters of allergic asthma, including the production of Th2 cytokines and the cysteinyl leukotriene LTC(4). Cysteinyl leukotrienes are primarily produced by mast cells, and these cells play a central role in allergic asthma. Mast cells express a high-affinity receptor for IgE (FcepsilonRI). Following its cross-linking, cells degranulate and release preformed inflammatory mediators (early phase) and synthesize and secrete cytokines/chemokines and leukotrienes (late phase). The mechanism by which nicotine modulates mast cell activation is unclear. Using alpha-bungarotoxin binding and quantitative PCR and PCR product sequencing, we showed that the rat mast/basophil cell line RBL-2H3 expresses nicotinic acetylcholine receptors (nAChRs) alpha7, alpha9, and alpha10; exposure to exceedingly low concentrations of nicotine (nanomolar), but not the biologically inactive metabolite cotinine, for > or = 8 h suppressed the late phase (leukotriene/cytokine production) but not degranulation (histamine and hexosaminidase release). These effects were unrelated to those of nicotine on intracellular free calcium concentration but were causally associated with the inhibition of cytosolic phospholipase A(2) activity and the PI3K/ERK/NF-kappaB pathway, including phosphorylation of Akt and ERK and nuclear translocation of NF-kappaB. The suppressive effect of nicotine on the late-phase response was blocked by the alpha7/alpha9-nAChR antagonists methyllycaconitine and alpha-bungarotoxin, as well as by small interfering RNA knockdown of alpha7-, alpha9-, or alpha10-nAChRs, suggesting a functional interaction between alpha7-, alpha9-, and alpha10-nAChRs that might explain the response of RBL cells to nanomolar concentrations of nicotine. This "hybrid" receptor might serve as a target for novel antiallergic/antiasthmatic therapies.

  4. Skin Mast Cells Protect Mice Against Vaccinia Virus by Triggering Mast Cell Receptor S1PR2 and Releasing Antimicrobial Peptides

    PubMed Central

    Wang, Zhenping; Lai, Yuping; Bernard, Jamie J; MacLeod, Daniel; Cogen, Anna L; Moss, Bernard; Di Nardo, Anna

    2011-01-01

    Mast cells (MCs) are well known effectors of allergic reactions and are considered sentinels in the skin and mucosa. In addition, through their production of cathelicidin, mast cells have the capacity to oppose invading pathogens. We therefore hypothesized that mast cells could act as sentinels in the skin against viral infections using antimicrobial peptides. Here, we demonstrate that mast cells react to Vaccinia virus (VV) and degranulate using a membrane-activated pathway that leads to antimicrobial peptide discharge and virus inactivation. This finding was supported using a mouse model of viral infection. Mast cell-deficient (Kitwsh−/−) mice were more susceptible to skin VV infection than the wild-type animals, while Kitwsh−/− mice reconstituted with mast cells in the skin showed a normal response to VV. Using mast cells derived from mice deficient in cathelicidin antimicrobial peptide, we showed that antimicrobial peptides are one important antiviral granule component in vivo skin infections. In conclusion, our paper demonstrates that: MC presence protects mice from VV skin infection. MC degranulation is required for protecting mice from VV. Neutralizing antibody to the L1 fusion entry protein of VV inhibits degranulation apparently by preventing S1PR2 activation by viral membrane lipids. Antimicrobial peptide release from mast cell granules is necessary to inactivate VV infectivity. PMID:22140255

  5. FAST Mast Structural Response to Axial Loading: Modeling and Verification

    NASA Technical Reports Server (NTRS)

    Knight, Norman F., Jr.; Elliott, Kenny B.; Templeton, Justin D.; Song, Kyongchan; Rayburn, Jeffery T.

    2012-01-01

    The International Space Station s solar array wing mast shadowing problem is the focus of this paper. A building-block approach to modeling and analysis is pursued for the primary structural components of the solar array wing mast structure. Starting with an ANSYS (Registered Trademark) finite element model, a verified MSC.Nastran (Trademark) model is established for a single longeron. This finite element model translation requires the conversion of several modeling and analysis features for the two structural analysis tools to produce comparable results for the single-longeron configuration. The model is then reconciled using test data. The resulting MSC.Nastran (Trademark) model is then extended to a single-bay configuration and verified using single-bay test data. Conversion of the MSC. Nastran (Trademark) single-bay model to Abaqus (Trademark) is also performed to simulate the elastic-plastic longeron buckling response of the single bay prior to folding.

  6. Autonomous Performance Monitoring System: Monitoring and Self-Tuning (MAST)

    NASA Technical Reports Server (NTRS)

    Peterson, Chariya; Ziyad, Nigel A.

    2000-01-01

    Maintaining the long-term performance of software onboard a spacecraft can be a major factor in the cost of operations. In particular, the task of controlling and maintaining a future mission of distributed spacecraft will undoubtedly pose a great challenge, since the complexity of multiple spacecraft flying in formation grows rapidly as the number of spacecraft in the formation increases. Eventually, new approaches will be required in developing viable control systems that can handle the complexity of the data and that are flexible, reliable and efficient. In this paper we propose a methodology that aims to maintain the accuracy of flight software, while reducing the computational complexity of software tuning tasks. The proposed Monitoring and Self-Tuning (MAST) method consists of two parts: a flight software monitoring algorithm and a tuning algorithm. The dependency on the software being monitored is mostly contained in the monitoring process, while the tuning process is a generic algorithm independent of the detailed knowledge on the software. This architecture will enable MAST to be applicable to different onboard software controlling various dynamics of the spacecraft, such as attitude self-calibration, and formation control. An advantage of MAST over conventional techniques such as filter or batch least square is that the tuning algorithm uses machine learning approach to handle uncertainty in the problem domain, resulting in reducing over all computational complexity. The underlying concept of this technique is a reinforcement learning scheme based on cumulative probability generated by the historical performance of the system. The success of MAST will depend heavily on the reinforcement scheme used in the tuning algorithm, which guarantees the tuning solutions exist.

  7. Induction of Mast Cell Accumulation by Tryptase via a Protease Activated Receptor-2 and ICAM-1 Dependent Mechanism

    PubMed Central

    Liu, Xin; Wang, Junling; Zhang, Huiyun; Zhan, Mengmeng; Chen, Hanqiu; Fang, Zeman; Xu, Chiyan; Chen, Huifang; He, Shaoheng

    2016-01-01

    Mast cells are primary effector cells of allergy, and recruitment of mast cells in involved tissue is one of the key events in allergic inflammation. Tryptase is the most abundant secretory product of mast cells, but little is known of its influence on mast cell accumulation. Using mouse peritoneal model, cell migration assay, and flow cytometry analysis, we investigated role of tryptase in recruiting mast cells. The results showed that tryptase induced up to 6.7-fold increase in mast cell numbers in mouse peritoneum following injection. Inhibitors of tryptase, an antagonist of PAR-2 FSLLRY-NH2, and pretreatment of mice with anti-ICAM-1, anti-CD11a, and anti-CD18 antibodies dramatically diminished tryptase induced mast cell accumulation. On the other hand, PAR-2 agonist peptides SLIGRL-NH2 and tc-LIGRLO-NH2 provoked mast cell accumulation following injection. These implicate that tryptase induced mast cell accumulation is dependent on its enzymatic activity, activation of PAR-2, and interaction between ICAM-1 and LFA-1. Moreover, induction of trans-endothelium migration of mast cells in vitro indicates that tryptase acts as a chemoattractant. In conclusion, provocation of mast cell accumulation by mast cell tryptase suggests a novel self-amplification mechanism of mast cell accumulation. Mast cell stabilizers as well as PAR-2 antagonist agents may be useful for treatment of allergic reactions. PMID:27378825

  8. Impact of Pretransplantation (18)F-Fluorodeoxyglucose-Positron Emission Tomography on Survival Outcomes after T Cell-Depleted Allogeneic Transplantation for Hodgkin Lymphoma.

    PubMed

    Reyal, Yasmin; Kayani, Irfan; Bloor, Adrian J C; Fox, Christopher P; Chakraverty, Ronjon; Sjursen, Ann-Marie; Fielding, Adele K; Ben Taylor, Marcus; Bishton, Mark J; Morris, Emma C; Thomson, Kirsty J; Russell, Nigel; Mackinnon, Stephen; Peggs, Karl S

    2016-07-01

    Pretransplant (18)F-fluorodeoxyglucose (FDG) positron emission tomography status is an important prognostic factor for outcomes after autologous stem cell transplantation (SCT) in Hodgkin lymphoma (HL), but its impact on outcomes after allogeneic SCT remains unclear. We retrospectively evaluated outcomes after T cell-depleted allogeneic SCT of 116 patients with nonprogressive HL according to pretransplant Deauville scores. Endpoints were overall survival (OS), progression-free survival (PFS), relapse rate (RR), and nonrelapse-related mortality (NRM). OS, PFS, and RR did not differ significantly between the Deauville 1 to 2 and Deauville 3 to 5 cohorts (OS: 77.5% versus 67.3%, P = .49; PFS: 59.4% versus 55.7%, P = .43; RR: 20.9% versus 22.6%, P = .28 at 4 years). Differences in PFS remained statistically nonsignificant when comparisons were made between Deauville 1 to 3 and Deauville 4 to 5 cohorts (60.9% versus 51.4%, P = .10), and RR remained very similar (21.5% versus 23.8%, P = .42). Multivariate analyses demonstrated trends toward significance for an effect of Deauville score on PFS (hazard ratio 1.82 for Deauville 4 to 5, P = .06) and for number of lines of prior therapy on OS (hazard ratio 2.34 for >5 lines, P = .10). The latter effect appeared to be driven by higher NRM rather than increased RR. Our findings suggest that Deauville score before allogeneic SCT in patients with nonprogressive HL has a relatively modest impact on survival outcomes in comparison with the impact in autologous SCT and that predictive values for the individual patient remain low, indicating that residual FDG-avid disease should not preclude allogeneic SCT. Furthermore, our findings bring into question the importance of attainment of metabolic complete response in this setting if it is at the expense of increasing NRM risk. PMID:27095691

  9. Cell depletion in mice that express diphtheria toxin receptor under the control of SiglecH encompasses more than plasmacytoid dendritic cells1

    PubMed Central

    Swiecki, Melissa; Wang, Yaming; Riboldi, Elena; Kim, Alfred H.J.; Dzutsev, Amiran; Gilfillan, Susan; Vermi, William; Ruedl, Christiane; Trinchieri, Giorgio; Colonna, Marco

    2014-01-01

    Plasmacytoid dendritic cells (pDC) produce type I interferon (IFN-I) in response to viruses and are routinely identified in mice by SiglecH expression. SiglecH is a sialic acid-binding immunoglobulin-like lectin that has an immunomodulatory role during viral infections. Here, we evaluated the impact of SiglecH deficiency on cytokine responses in the presence and absence of pDC. We found that lack of SiglecH enhanced IFN-I responses to viral infection regardless of whether pDC were depleted or not. We also examined the expression pattern of SiglecH in this study. We observed that SiglecH was expressed by specialized macrophages and progenitors of classical DC (cDC) and pDC. Accordingly, marginal zone macrophages and pDC precursors were eliminated in newly generated SiglecH-DTR Tg mice but not CLEC4C-DTR Tg mice after diphtheria toxin (DT) treatment. Using two different bacterial models, we found that SiglecH-DTR Tg mice injected with DT had altered bacterial uptake and were more susceptible to lethal Listeria monocytogenes infection than DT-treated CLEC4C-DTR Tg mice. Taken together, our findings suggest that lack of SiglecH may affect cytokine responses by cell types other than pDC during viral infections perhaps by altering viral distribution or burden and that cell depletion in SiglecH-DTR Tg mice encompasses more than pDC. PMID:24683186

  10. Acute GVHD in patients receiving IL-15/4-1BBL activated NK cells following T-cell-depleted stem cell transplantation.

    PubMed

    Shah, Nirali N; Baird, Kristin; Delbrook, Cynthia P; Fleisher, Thomas A; Kohler, Mark E; Rampertaap, Shakuntala; Lemberg, Kimberly; Hurley, Carolyn K; Kleiner, David E; Merchant, Melinda S; Pittaluga, Stefania; Sabatino, Marianna; Stroncek, David F; Wayne, Alan S; Zhang, Hua; Fry, Terry J; Mackall, Crystal L

    2015-01-29

    Natural killer (NK) cells can enhance engraftment and mediate graft-versus-leukemia following allogeneic hematopoietic stem cell transplantation (HSCT), but the potency of graft-versus-leukemia mediated by naturally reconstituting NK cells following HSCT is limited. Preclinical studies demonstrate that activation of NK cells using interleukin-15 (IL-15) plus 4-1BBL upregulates activating receptor expression and augments killing capacity. In an effort to amplify the beneficial effects of NK cells post-HSCT, we conducted a first-in-human trial of adoptive transfer of donor-derived IL-15/4-1BBL-activated NK cells (aNK-DLI) following HLA-matched, T-cell-depleted (1-2 × 10(4) T cells/kg) nonmyeloablative peripheral blood stem cell transplantation in children and young adults with ultra-high-risk solid tumors. aNK-DLI were CD3(+)-depleted, CD56(+)-selected lymphocytes, cultured for 9 to 11 days with recombinant human IL-15 plus 4-1BBL(+)IL-15Rα(+) artificial antigen-presenting cells. aNK-DLI demonstrated potent killing capacity and displayed high levels of activating receptor expression. Five of 9 transplant recipients experienced acute graft-versus-host disease (GVHD) following aNK-DLI, with grade 4 GVHD observed in 3 subjects. GVHD was more common in matched unrelated donor vs matched sibling donor recipients and was associated with higher donor CD3 chimerism. Given that the T-cell dose was below the threshold required for GVHD in this setting, we conclude that aNK-DLI contributed to the acute GVHD observed, likely by augmenting underlying T-cell alloreactivity. This trial was registered at www.clinicaltrials.gov as #NCT01287104. PMID:25452614

  11. Acute GVHD in patients receiving IL-15/4-1BBL activated NK cells following T-cell-depleted stem cell transplantation.

    PubMed

    Shah, Nirali N; Baird, Kristin; Delbrook, Cynthia P; Fleisher, Thomas A; Kohler, Mark E; Rampertaap, Shakuntala; Lemberg, Kimberly; Hurley, Carolyn K; Kleiner, David E; Merchant, Melinda S; Pittaluga, Stefania; Sabatino, Marianna; Stroncek, David F; Wayne, Alan S; Zhang, Hua; Fry, Terry J; Mackall, Crystal L

    2015-01-29

    Natural killer (NK) cells can enhance engraftment and mediate graft-versus-leukemia following allogeneic hematopoietic stem cell transplantation (HSCT), but the potency of graft-versus-leukemia mediated by naturally reconstituting NK cells following HSCT is limited. Preclinical studies demonstrate that activation of NK cells using interleukin-15 (IL-15) plus 4-1BBL upregulates activating receptor expression and augments killing capacity. In an effort to amplify the beneficial effects of NK cells post-HSCT, we conducted a first-in-human trial of adoptive transfer of donor-derived IL-15/4-1BBL-activated NK cells (aNK-DLI) following HLA-matched, T-cell-depleted (1-2 × 10(4) T cells/kg) nonmyeloablative peripheral blood stem cell transplantation in children and young adults with ultra-high-risk solid tumors. aNK-DLI were CD3(+)-depleted, CD56(+)-selected lymphocytes, cultured for 9 to 11 days with recombinant human IL-15 plus 4-1BBL(+)IL-15Rα(+) artificial antigen-presenting cells. aNK-DLI demonstrated potent killing capacity and displayed high levels of activating receptor expression. Five of 9 transplant recipients experienced acute graft-versus-host disease (GVHD) following aNK-DLI, with grade 4 GVHD observed in 3 subjects. GVHD was more common in matched unrelated donor vs matched sibling donor recipients and was associated with higher donor CD3 chimerism. Given that the T-cell dose was below the threshold required for GVHD in this setting, we conclude that aNK-DLI contributed to the acute GVHD observed, likely by augmenting underlying T-cell alloreactivity. This trial was registered at www.clinicaltrials.gov as #NCT01287104.

  12. Hemorrhage Exacerbates Radiation Effects on Survival, Leukocytopenia, Thrombopenia, Erythropenia, Bone Marrow Cell Depletion and Hematopoiesis, and Inflammation-Associated microRNAs Expression in Kidney.

    PubMed

    Kiang, Juliann G; Smith, Joan T; Anderson, Marsha N; Swift, Joshua M; Christensen, Christine L; Gupta, Paridhi; Balakathiresan, Nagaraja; Maheshwari, Radha K

    2015-01-01

    Exposure to high-dose radiation results in detrimental effects on survival. The effects of combined trauma, such as radiation in combination with hemorrhage, the typical injury of victims exposed to a radiation blast, on survival and hematopoietic effects have yet to be understood. The purpose of this study was to evaluate the effects of radiation injury (RI) combined with hemorrhage (i.e., combined injury, CI) on survival and hematopoietic effects, and to investigate whether hemorrhage (Hemo) enhanced RI-induced mortality and hematopoietic syndrome. Male CD2F1 mice (10 weeks old) were given one single exposure of γ- radiation (60Co) at various doses (0.6 Gy/min). Within 2 hr after RI, animals under anesthesia were bled 0% (Sham) or 20% (Hemo) of total blood volume via the submandibular vein. In these mice, Hemo reduced the LD50/30 for 30-day survival from 9.1 Gy (RI) to 8.75 Gy (CI) with a DMF of 1.046. RI resulted in leukocytopenia, thrombopenia, erythropenia, and bone marrow cell depletion, but decreased the caspase-3 activation response. RI increased IL-1β, IL-6, IL-17A, and TNF-α concentrations in serum, bone marrow, ileum, spleen, and kidney. Some of these adverse alterations were magnified by CI. Erythropoietin production was increased in kidney and blood more after CI than RI. Furthermore, CI altered the global miRNAs expression in kidney and the ingenuity pathway analysis showed that miRNAs viz., let-7e, miR-30e and miR-29b that were associated with hematopoiesis and inflammation. This study provides preliminary evidence that non-lethal Hemo exacerbates RI-induced mortality and cell losses associated with high-dose γ-radiation. We identified some of the initial changes occurring due to CI which may have facilitated in worsening the injury and hampering the recovery of animals ultimately resulting in higher mortality. PMID:26422254

  13. Hemorrhage Exacerbates Radiation Effects on Survival, Leukocytopenia, Thrombopenia, Erythropenia, Bone Marrow Cell Depletion and Hematopoiesis, and Inflammation-Associated microRNAs Expression in Kidney

    PubMed Central

    Kiang, Juliann G.; Smith, Joan T.; Anderson, Marsha N.; Swift, Joshua M.; Christensen, Christine L.; Gupta, Paridhi; Balakathiresan, Nagaraja; Maheshwari, Radha K.

    2015-01-01

    Exposure to high-dose radiation results in detrimental effects on survival. The effects of combined trauma, such as radiation in combination with hemorrhage, the typical injury of victims exposed to a radiation blast, on survival and hematopoietic effects have yet to be understood. The purpose of this study was to evaluate the effects of radiation injury (RI) combined with hemorrhage (i.e., combined injury, CI) on survival and hematopoietic effects, and to investigate whether hemorrhage (Hemo) enhanced RI-induced mortality and hematopoietic syndrome. Male CD2F1 mice (10 weeks old) were given one single exposure of γ- radiation (60Co) at various doses (0.6 Gy/min). Within 2 hr after RI, animals under anesthesia were bled 0% (Sham) or 20% (Hemo) of total blood volume via the submandibular vein. In these mice, Hemo reduced the LD50/30 for 30-day survival from 9.1 Gy (RI) to 8.75 Gy (CI) with a DMF of 1.046. RI resulted in leukocytopenia, thrombopenia, erythropenia, and bone marrow cell depletion, but decreased the caspase-3 activation response. RI increased IL-1β, IL-6, IL-17A, and TNF-α concentrations in serum, bone marrow, ileum, spleen, and kidney. Some of these adverse alterations were magnified by CI. Erythropoietin production was increased in kidney and blood more after CI than RI. Furthermore, CI altered the global miRNAs expression in kidney and the ingenuity pathway analysis showed that miRNAs viz., let-7e, miR-30e and miR-29b that were associated with hematopoiesis and inflammation. This study provides preliminary evidence that non-lethal Hemo exacerbates RI-induced mortality and cell losses associated with high-dose γ-radiation. We identified some of the initial changes occurring due to CI which may have facilitated in worsening the injury and hampering the recovery of animals ultimately resulting in higher mortality. PMID:26422254

  14. Functional Cure of SIVagm Infection in Rhesus Macaques Results in Complete Recovery of CD4+ T Cells and Is Reverted by CD8+ Cell Depletion

    PubMed Central

    Pandrea, Ivona; Gaufin, Thaidra; Gautam, Rajeev; Kristoff, Jan; Mandell, Daniel; Montefiori, David; Keele, Brandon F.; Ribeiro, Ruy M.; Veazey, Ronald S.; Apetrei, Cristian

    2011-01-01

    Understanding the mechanism of infection control in elite controllers (EC) may shed light on the correlates of control of disease progression in HIV infection. However, limitations have prevented a clear understanding of the mechanisms of elite controlled infection, as these studies can only be performed at randomly selected late time points in infection, after control is achieved, and the access to tissues is limited. We report that SIVagm infection is elite-controlled in rhesus macaques (RMs) and therefore can be used as an animal model for EC HIV infection. A robust acute infection, with high levels of viral replication and dramatic mucosal CD4+ T cell depletion, similar to pathogenic HIV-1/SIV infections of humans and RMs, was followed by complete and durable control of SIVagm replication, defined as: undetectable VLs in blood and tissues beginning 72 to 90 days postinoculation (pi) and continuing at least 4 years; seroreversion; progressive recovery of mucosal CD4+ T cells, with complete recovery by 4 years pi; normal levels of T cell immune activation, proliferation, and apoptosis; and no disease progression. This “functional cure” of SIVagm infection in RMs could be reverted after 4 years of control of infection by depleting CD8 cells, which resulted in transient rebounds of VLs, thus suggesting that control may be at least in part immune mediated. Viral control was independent of MHC, partial APOBEC restriction was not involved in SIVagm control in RMs and Trim5 genotypes did not impact viral replication. This new animal model of EC lentiviral infection, in which complete control can be predicted in all cases, permits research on the early events of infection in blood and tissues, before the defining characteristics of EC are evident and when host factors are actively driving the infection towards the EC status. PMID:21829366

  15. The progress and promise of zebrafish as a model to study mast cells.

    PubMed

    Prykhozhij, Sergey V; Berman, Jason N

    2014-09-01

    Immunological and hematological research using the zebrafish (Danio rerio) has significantly advanced our understanding of blood lineage ontology, cellular functions and mechanisms, and provided opportunities for disease modeling. Mast cells are an immunological cell type involved in innate and adaptive immune systems, hypersensitivity reactions and cancer progression. The application of zebrafish to study mast cell biology exploits the developmental and imaging opportunities inherent in this model system to enable detailed genetic and molecular studies of this lineage outside of traditional mammalian models. In this review, we first place the importance of mast cell research in zebrafish into the context of comparative studies of mast cells in other fish species and highlight its advantages due to superior experimental tractability and direct visualization in transparent embryos. We discuss current and future tools for mast cell research in zebrafish and the notable results of using zebrafish for understanding mast cell fate determination and our development of a systemic mastocytosis model.

  16. First Results from a Charged Fusion Products Diagnostic at MAST

    NASA Astrophysics Data System (ADS)

    Perez, Ramona V.; Allan, Scott Y.; Boeglin, Werner U.; Cecconello, Marco; McClements, Ken G.; Darrow, Douglass S.; MAST Team

    2013-10-01

    We designed, built and installed in MAST a 4-channel solid-state detector array for the detection of the charged deuterium-deuterium fusion products protons and tritons. The array has been mounted at the end of the reciprocating probe arm in MAST allowing it to sample a range of radial positions. First data have been taken in August 2013. The detector signals have been digitized with a 60 MHz sampling rate and have been continuously recorded during plasma discharges. Protons and tritons were readily identified and counted. The observed count rates showed clear dependence on the neutral beam power and were modulated synchronous with saw-teeth. Comparison with data obtained from the MAST neutron camera and the fission chamber neutron detector is planned. We found that time resolutions as low as at least 1 ms were achievable. The detector performance and first analysis results for various plasma scenarios will be presented. Supported in part by DOE grant DE-SC0001157.

  17. Weather model verification using Sodankylä mast measurements

    NASA Astrophysics Data System (ADS)

    Kangas, Markku; Rontu, Laura; Fortelius, Carl; Aurela, Mika; Poikonen, Antti

    2016-04-01

    Sodankylä, in the heart of Arctic Research Centre of the Finnish Meteorological Institute (FMI ARC) in northern Finland, is an ideal site for atmospheric and environmental research in the boreal and sub-Arctic zone. With temperatures ranging from -50 to +30 °C, it provides a challenging testing ground for numerical weather forecasting (NWP) models as well as weather forecasting in general. An extensive set of measurements has been carried out in Sodankylä for more than 100 years. In 2000, a 48 m-high micrometeorological mast was erected in the area. In this article, the use of Sodankylä mast measurements in NWP model verification is described. Starting in 2000, with the NWP model HIRLAM and Sodankylä measurements, the verification system has now been expanded to include comparisons between 12 NWP models and seven measurement masts, distributed across Europe. A case study, comparing forecasted and observed radiation fluxes, is also presented. It was found that three different radiation schemes, applicable in NWP model HARMONIE-AROME, produced somewhat different downwelling longwave radiation fluxes during cloudy days, which however did not change the overall cold bias of the predicted screen-level temperature.

  18. Weather model verification using Sodankylä mast measurements

    NASA Astrophysics Data System (ADS)

    Kangas, M.; Rontu, L.; Fortelius, C.; Aurela, M.; Poikonen, A.

    2015-12-01

    Sodankylä, in the heart of Arctic Research Centre of the Finnish Meteorological Institute (FMI ARC) in northern Finland, is an ideal site for atmospheric and environmental research in the boreal and sub-arctic zone. With temperatures ranging from -50 to +30 °C, it provides a challenging testing ground for numerical weather forecasting (NWP) models as well as weather forecasting in general. An extensive set of measurements has been carried out in Sodankylä for more than 100 years. In 2000, a 48 m high micrometeorological mast was erected in the area. In this article, the use of Sodankylä mast measurements in NWP model verification is described. Started in 2000 with NWP model HIRLAM and Sodankylä measurements, the verification system has now been expanded to include comparisons between 12 NWP models and seven measurement masts. A case study, comparing forecasted and observed radiation fluxes, is also presented. It was found that three different radiation schemes, applicable in NWP model HARMONIE-AROME, produced during cloudy days somewhat different downwelling long-wave radiation fluxes, which however did not change the overall cold bias of the predicted screen-level temperature.

  19. Amarogentin Displays Immunomodulatory Effects in Human Mast Cells and Keratinocytes

    PubMed Central

    Wölfle, Ute; Haarhaus, Birgit; Schempp, Christoph M.

    2015-01-01

    Keratinocytes express the bitter taste receptors TAS2R1 and TAS2R38. Amarogentin as an agonist for TAS2R1 and other TAS2Rs promotes keratinocyte differentiation. Similarly, mast cells are known to express bitter taste receptors. The aim of this study was to assess whether bitter compounds display immunomodulatory effects on these immunocompetent cells in the skin, so that they might be a target in chronic inflammatory diseases such as atopic dermatitis and psoriasis. Here, we investigated the impact of amarogentin on substance P-induced release of histamine and TNF-α from the human mast cell line LAD-2. Furthermore, the effect of amarogentin on HaCaT keratinocytes costimulated with TNF-α and histamine was investigated. Amarogentin inhibited in LAD-2 cells substance P-induced production of newly synthesized TNF-α, but the degranulation and release of stored histamine were not affected. In HaCaT keratinocytes histamine and TNF-α induced IL-8 and MMP-1 expression was reduced by amarogentin to a similar extent as with azelastine. In conclusion amarogentin displays immunomodulatory effects in the skin by interacting with mast cells and keratinocytes. PMID:26600671

  20. Eigensystem realization algorithm modal identification experiences with mini-mast

    NASA Technical Reports Server (NTRS)

    Pappa, Richard S.; Schenk, Axel; Noll, Christopher

    1992-01-01

    This paper summarizes work performed under a collaborative research effort between the National Aeronautics and Space Administration (NASA) and the German Aerospace Research Establishment (DLR, Deutsche Forschungsanstalt fur Luft- und Raumfahrt). The objective is to develop and demonstrate system identification technology for future large space structures. Recent experiences using the Eigensystem Realization Algorithm (ERA), for modal identification of Mini-Mast, are reported. Mini-Mast is a 20 m long deployable space truss used for structural dynamics and active vibration-control research at the Langley Research Center. A comprehensive analysis of 306 frequency response functions (3 excitation forces and 102 displacement responses) was performed. Emphasis is placed on two topics of current research: (1) gaining an improved understanding of ERA performance characteristics (theory vs. practice); and (2) developing reliable techniques to improve identification results for complex experimental data. Because of nonlinearities and numerous local modes, modal identification of Mini-Mast proved to be surprisingly difficult. Methods were available, ERA, for obtaining detailed, high-confidence results.

  1. The Role of Mast Cells in Alzheimer's Disease.

    PubMed

    Shaik-Dasthagirisaheb, Yasdani B; Conti, Pio

    2016-01-01

    Immunity and inflammation are deeply involved in Alzheimer's disease. The most important properties of pathological Alzheimer's disease are the extracellular deposits of amyloid â-protein plaque aggregates along with other unknown mutated proteins, which are implicated in immunity and inflammation. Mast cells are found in the brain of all mammalian species and in the periphery, and their biological mediators, including cytokines/chemokines, arachidonic acid products and stored enzymes, play an import role in Alzheimer's disease. Cytokines/chemokines, which are generated mostly by microglia and astrocytes in Alzheimer's disease, contribute to nearly every aspect of neuroinflammation and amyloid â-protein plaque aggregates may induce in mast cells the release of a plethora of mediators, including pro-inflammatory cytokines/chemokines such as interleukin-1, interleukin-6, interleukin-8, interleukin-10, tumor necrosis factor-alpha, vascular endothelial growth factor, transforming growth factor beta, CXCL8 and CCL2-3-4. These proinflammatory cytokines/chemokines are prominent mediators of neuroinflammation in brain disorders such as Alzheimer's disease, and their inhibition may be associated with improved recovery. In this review, we summarize the current knowledge regarding the roles of mast cell mediators (stored and de novo synthesis) in the pathogenesis of Alzheimer's disease. PMID:27629855

  2. Acrolein induction of oxidative stress and degranulation in mast cells.

    PubMed

    Hochman, Daniel J; Collaco, Christopher R; Brooks, Edward G

    2014-08-01

    Increases in asthma worldwide have been associated epidemiologically with expanding urban air pollution. The mechanistic relationship between airway hyper-responsiveness, inflammation, and ambient airborne triggers remains ambiguous. Acrolein, a ubiquitous aldehyde pollutant, is a product of incomplete combustion reactions. Acrolein is abundant in cigarette smoke, effluent from industrial smokestacks, diesel exhaust, and even hot oil cooking vapors. Acrolein is a potent airway irritant and can induce airway hyper-responsiveness and inflammation in the lungs of animal models. In the present study, we utilized the mast cell analog, RBL-2H3, to interrogate the responses of cells relevant to airway inflammation and allergic responses as a model for the induction of asthma-like conditions upon exposure to acrolein. We hypothesized that acrolein would induce oxidative stress and degranulation in airway mast cells. Our results indicate that acrolein at 1 ppm initiated degranulation and promoted the generation of reactive oxygen species (ROS). Introduction of antioxidants to the system significantly reduced both ROS generation and degranulation. At higher levels of exposure (above 100 ppm), RBL-2H3 cells displayed signs of severe toxicity. This experimental data indicates acrolein can induce an allergic inflammation in mast cell lines, and the initiation of degranulation was moderated by the application of antioxidants.

  3. Mast cells in canine cutaneous hemangioma, hemangiosarcoma and mammary tumors.

    PubMed

    Woldemeskel, Moges; Rajeev, Sreekumari

    2010-02-01

    Mast cell count (MCC) in 45 dogs with cutaneous hemangioma (HA, n = 12), hemangiosarcoma (HSA, n = 12), mammary adenoma (AD, n = 9) and mammary adenocarcinoma (AC, n = 12) was made using Toluidine blue stained sections. Antibodies against endothelial cell markers, Factor VIII and VEGF were used to visualize and determine the hot spot micro-vessel density (MVD). Total MCC and MCC along the invasive edges were significantly higher (p < 0.001) in canine mammary AC than in AD. The total MCC did not significantly differ (p > 0.05), in HSAs (8.6 +/- 3.3) than in HAs (5.5 +/- 2.8). There is a positive correlation (r = 0.14) between the hot spot MCC and MVD in mammary AC, although not significant (p = 0.3172), indicating that mast cells are associated with angiogenesis in canine mammary AC. This study suggests that mast cells may play an important role in neovascularization of canine cutaneous vascular and mammary neoplasms. Detailed studies encompassing correlation of MCC and MVD with clinical outcomes and prognosis in these neoplasms are recommended.

  4. Amarogentin Displays Immunomodulatory Effects in Human Mast Cells and Keratinocytes.

    PubMed

    Wölfle, Ute; Haarhaus, Birgit; Schempp, Christoph M

    2015-01-01

    Keratinocytes express the bitter taste receptors TAS2R1 and TAS2R38. Amarogentin as an agonist for TAS2R1 and other TAS2Rs promotes keratinocyte differentiation. Similarly, mast cells are known to express bitter taste receptors. The aim of this study was to assess whether bitter compounds display immunomodulatory effects on these immunocompetent cells in the skin, so that they might be a target in chronic inflammatory diseases such as atopic dermatitis and psoriasis. Here, we investigated the impact of amarogentin on substance P-induced release of histamine and TNF-α from the human mast cell line LAD-2. Furthermore, the effect of amarogentin on HaCaT keratinocytes costimulated with TNF-α and histamine was investigated. Amarogentin inhibited in LAD-2 cells substance P-induced production of newly synthesized TNF-α, but the degranulation and release of stored histamine were not affected. In HaCaT keratinocytes histamine and TNF-α induced IL-8 and MMP-1 expression was reduced by amarogentin to a similar extent as with azelastine. In conclusion amarogentin displays immunomodulatory effects in the skin by interacting with mast cells and keratinocytes. PMID:26600671

  5. The Role of Mast Cells in Alzheimer's Disease.

    PubMed

    Shaik-Dasthagirisaheb, Yasdani B; Conti, Pio

    2016-01-01

    Immunity and inflammation are deeply involved in Alzheimer's disease. The most important properties of pathological Alzheimer's disease are the extracellular deposits of amyloid â-protein plaque aggregates along with other unknown mutated proteins, which are implicated in immunity and inflammation. Mast cells are found in the brain of all mammalian species and in the periphery, and their biological mediators, including cytokines/chemokines, arachidonic acid products and stored enzymes, play an import role in Alzheimer's disease. Cytokines/chemokines, which are generated mostly by microglia and astrocytes in Alzheimer's disease, contribute to nearly every aspect of neuroinflammation and amyloid â-protein plaque aggregates may induce in mast cells the release of a plethora of mediators, including pro-inflammatory cytokines/chemokines such as interleukin-1, interleukin-6, interleukin-8, interleukin-10, tumor necrosis factor-alpha, vascular endothelial growth factor, transforming growth factor beta, CXCL8 and CCL2-3-4. These proinflammatory cytokines/chemokines are prominent mediators of neuroinflammation in brain disorders such as Alzheimer's disease, and their inhibition may be associated with improved recovery. In this review, we summarize the current knowledge regarding the roles of mast cell mediators (stored and de novo synthesis) in the pathogenesis of Alzheimer's disease.

  6. Anti-allergic activity of R-phycocyanin from Porphyra haitanensis in antigen-sensitized mice and mast cells.

    PubMed

    Liu, Qingmei; Wang, Youzhao; Cao, Minjie; Pan, Tzuming; Yang, Yang; Mao, Haiyan; Sun, Lechang; Liu, Guangming

    2015-04-01

    The prevalence of food allergy has increased in Asian countries. Marine algae have been proposed as the potential resource for anti-allergic therapeutics. The present study was aimed at isolating R-phycocyanin (RPC) from Porphyra haitanensis and determining the anti-allergy potential of RPC in antigen-sensitized mice and mast cells. In animal experiments, RPC could effectively reduce tropomyosin (TM)-specific immunoglobulin E (IgE) and histamine levels, alleviate allergy symptoms and jejunum tissue inflammation in mice, and inhibit the expression and release of cytokines (interleukin-4 (IL-4) and IL-13) in peritoneal lavage fluid. In spleen lymphocyte experiments, high purity of RPC skewed the immunological function of CD4(+) T cells towards Th1 activity. A higher expression of interferon (IFN)-γ was induced by a synergistic effect of TM and RPC. Through the Jun N-terminal kinase and Janus kinase 2 signaling pathways, IFN-γ synthesis was induced by RPC in combination with TM. Anti-allergic effect of RPC was evaluated in IgE-mediated rat mast RBL-2H3 cells. The results demonstrated that RPC inhibited allergy markers, including the release of β-hexosaminidase, histamine and ROS in antigen-sensitized RBL-2H3 cells. RPC also suppressed the production of pro-inflammatory factors (IL-4 and tumor necrosis factor-α). In conclusion, RPC decreased allergic sensitization against TM by blocking Th2 cell polarization as well as suppressed the release of allergic-mediators in antigen-stimulated mast cells. It may be used as a functional food component or active pharmaceutical ingredient for allergic patients.

  7. Anti-allergic activity of R-phycocyanin from Porphyra haitanensis in antigen-sensitized mice and mast cells.

    PubMed

    Liu, Qingmei; Wang, Youzhao; Cao, Minjie; Pan, Tzuming; Yang, Yang; Mao, Haiyan; Sun, Lechang; Liu, Guangming

    2015-04-01

    The prevalence of food allergy has increased in Asian countries. Marine algae have been proposed as the potential resource for anti-allergic therapeutics. The present study was aimed at isolating R-phycocyanin (RPC) from Porphyra haitanensis and determining the anti-allergy potential of RPC in antigen-sensitized mice and mast cells. In animal experiments, RPC could effectively reduce tropomyosin (TM)-specific immunoglobulin E (IgE) and histamine levels, alleviate allergy symptoms and jejunum tissue inflammation in mice, and inhibit the expression and release of cytokines (interleukin-4 (IL-4) and IL-13) in peritoneal lavage fluid. In spleen lymphocyte experiments, high purity of RPC skewed the immunological function of CD4(+) T cells towards Th1 activity. A higher expression of interferon (IFN)-γ was induced by a synergistic effect of TM and RPC. Through the Jun N-terminal kinase and Janus kinase 2 signaling pathways, IFN-γ synthesis was induced by RPC in combination with TM. Anti-allergic effect of RPC was evaluated in IgE-mediated rat mast RBL-2H3 cells. The results demonstrated that RPC inhibited allergy markers, including the release of β-hexosaminidase, histamine and ROS in antigen-sensitized RBL-2H3 cells. RPC also suppressed the production of pro-inflammatory factors (IL-4 and tumor necrosis factor-α). In conclusion, RPC decreased allergic sensitization against TM by blocking Th2 cell polarization as well as suppressed the release of allergic-mediators in antigen-stimulated mast cells. It may be used as a functional food component or active pharmaceutical ingredient for allergic patients. PMID:25746371

  8. Mast cells promote scar remodeling and functional recovery after spinal cord injury via mouse mast cell protease 6.

    PubMed

    Vangansewinkel, Tim; Geurts, Nathalie; Quanten, Kirsten; Nelissen, Sofie; Lemmens, Stefanie; Geboes, Lies; Dooley, Dearbhaile; Vidal, Pia M; Pejler, Gunnar; Hendrix, Sven

    2016-05-01

    An important barrier for axon regeneration and recovery after traumatic spinal cord injury (SCI) is attributed to the scar that is formed at the lesion site. Here, we investigated the effect of mouse mast cell protease (mMCP) 6, a mast cell (MC)-specific tryptase, on scarring and functional recovery after a spinal cord hemisection injury. Functional recovery was significantly impaired in both MC-deficient and mMCP6-knockout (mMCP6(-/-)) mice after SCI compared with wild-type control mice. This decrease in locomotor performance was associated with an increased lesion size and excessive scarring at the injury site. Axon growth-inhibitory chondroitin sulfate proteoglycans and the extracellular matrix components fibronectin, laminin, and collagen IV were significantly up-regulated in MC-deficient and mMCP6(-/-) mice, with an increase in scar volume between 23 and 32%. A degradation assay revealed that mMCP6 directly cleaves fibronectin and collagen IV in vitro In addition, gene expression levels of the scar components fibronectin, aggrecan, and collagen IV were increased up to 6.8-fold in mMCP6(-/-) mice in the subacute phase after injury. These data indicate that endogenous mMCP6 has scar-suppressing properties after SCI via indirect cleavage of axon growth-inhibitory scar components and alteration of the gene expression profile of these factors.-Vangansewinkel, T., Geurts, N., Quanten, K., Nelissen, S., Lemmens, S., Geboes, L., Dooley, D., Vidal, P. M., Pejler, G., Hendrix, S. Mast cells promote scar remodeling and functional recovery after spinal cord injury via mouse mast cell protease 6.

  9. Mitigation of MHD induced fast-ion redistribution in MAST and implications for MAST-Upgrade design

    NASA Astrophysics Data System (ADS)

    Keeling, D. L.; Barrett, T. R.; Cecconello, M.; Challis, C. D.; Hawkes, N.; Jones, O. M.; Klimek, I.; McClements, K. G.; Meakins, A.; Milnes, J.; Turnyanskiy, M.; the MAST Team

    2015-01-01

    The phenomenon of the redistribution of neutral beam fast ions due to magnetohydrodynamic (MHD) activity in plasma has been observed on many tokamaks and more recently has been a focus of research on MAST (Turnyanskiy et al 2013 Nucl. Fusion 53 053016). n = 1 fishbone modes are observed to cause a large decrease in the neutron emission rate indicating the existence of a significant perturbation of the fast-ion population in the plasma. Theoretical work on fishbone modes states that the fast-ion distribution itself acts as the source of free energy driving the modes that cause the redistribution. Therefore a series of experiments have been carried out on MAST to investigate a range of plasma densities at two neutral-beam power levels to determine the region within this parameter space in which fishbone activity and consequent fast-ion redistribution is suppressed. Analysis of these experiments shows complete suppression of fishbone activity at high densities with increasing activity and fast-ion redistribution at lower densities and higher neutral-beam power, accompanied by strong evidence that the redistribution effect primarily affects a specific region in the plasma core with a weaker effect over a wider region of the plasma. The results also indicate the existence of correlations between gradients in the modelled fast-ion distribution function, the amplitude and growth rate of the fishbone modes, and the magnitude of the redistribution effect. The same analysis has been carried out on models of MAST-Upgrade baseline plasma scenarios to determine whether significant fast-ion redistribution due to fishbone modes is likely to occur in that device. A simple change to the neutral-beam injector geometry is proposed which is shown to have a significant mitigating effect in terms of the fishbone mode drive and is therefore expected to allow effective plasma heating and current drive over a wider range of plasma conditions in MAST-Upgrade.

  10. High Disease-Free Survival with Enhanced Protection against Relapse after Double-Unit Cord Blood Transplantation When Compared with T Cell-Depleted Unrelated Donor Transplantation in Patients with Acute Leukemia and Chronic Myelogenous Leukemia.

    PubMed

    Ponce, Doris M; Hilden, Patrick; Devlin, Sean M; Maloy, Molly; Lubin, Marissa; Castro-Malaspina, Hugo; Dahi, Parastoo; Hsu, Katharine; Jakubowski, Ann A; Kernan, Nancy A; Koehne, Guenther; O'Reilly, Richard J; Papadopoulos, Esperanza B; Perales, Miguel-Angel; Sauter, Craig; Scaradavou, Andromachi; Tamari, Roni; van den Brink, Marcel R M; Young, James W; Giralt, Sergio; Barker, Juliet N

    2015-11-01

    Double-unit cord blood (DCB) grafts are a rapidly available stem cell source for adults with high-risk leukemias. However, how disease-free survival (DFS) after DCB transplantation (DCBT) compares to that of unrelated donor transplantation (URDT) is not fully established. We analyzed 166 allograft recipients (66 8/8 HLA-matched URDT, 45 7/8 HLA-matched URDT, and 55 DCBT) ages 16 to 60 years with high-risk acute leukemia or chronic myelogenous leukemia (CML). URDT and DCBT recipients were similar except DCBT recipients were more likely to have lower weight and non-European ancestry and to receive intermediate-intensity conditioning. All URDT recipients received a CD34(+) cell-selected (T cell-depleted) graft. Overall, differences between the 3-year transplantation-related mortality were not significant (8/8 URDT, 18%; 7/8 URDT, 39%; and DCBT, 24%; P = .108), whereas the 3-year relapse risk was decreased after DCBT (8/8 URDT, 23%; 7/8 URDT, 20%; and DCBT 9%, P = .037). Three-year DFS was 57% in 8/8 URDT, 41% in 7/8 URDT, and 68% in DCBT recipients (P = .068), and the 3-year DFS in DCBT recipients was higher than that of 7/8 URDT recipients (P = .021). In multivariate analysis in acute leukemia patients, factors adversely associated with DFS were female gender (hazard ratio [HR], 1.68; P = .031), diagnosis of acute lymphoblastic leukemia (HR, 2.09; P = .004), and 7/8 T cell-depleted URDT (HR, 1.91; P = .037). High DFS can be achieved in adults with acute leukemia and CML with low relapse rates after DCBT. Our findings support performing DCBT in adults in preference to HLA-mismatched T cell-depleted URDT and suggest DCBT is a readily available alternative to T cell-depleted 8/8 URDT, especially in patients requiring urgent transplantation.

  11. Continuous antigenic stimulation of DO11.10 TCR transgenic mice in the presence or absence of IL-1β: possible implications for mechanisms of T cell depletion in HIV disease1

    PubMed Central

    Ladell, Kristin; Hazenberg, Mette D.; Fitch, Mark; Emson, Claire; McEvoy-Hein Asgarian, Bridget K.; Mold, Jeff E.; Miller, Corey; Busch, Robert; Price, David A.; Hellerstein, Marc K.; McCune, Joseph M.

    2015-01-01

    Untreated HIV disease is associated with chronic immune activation and CD4+ T cell depletion. A variety of mechanisms have been invoked to account for CD4+ T cell depletion in this context, but the quantitative contributions of these proposed mechanisms over time remains unclear. We turned to the DO11.10 TCR transgenic (tg) mouse model, where OVA is recognized in the context of H-2d, to explore the impact of chronic antigenic stimulation on CD4+ T cell dynamics. To model dichotomous states of persistent antigen exposure in the presence or absence of proinflammatory stimulation, we administered OVA peptide (OVAp) to these mice on a continuous basis with or without the prototypic proinflammatory cytokine, interleukin 1β (IL-1β). In both cases, circulating antigen-specific CD4+ T cells were depleted. However, in the absence of IL-1β, there was limited proliferation and effector/memory conversion of antigen-specific T cells, depletion of peripheral CD4+ T cells in hematolymphoid organs, and systemic induction of regulatory FoxP3+CD4+ T cells, as often observed in late-stage HIV disease. By contrast, when OVAp was administered in the presence of IL-1β, effector/memory phenotype T cells expanded and the typical symptoms of heightened immune activation were observed. Acknowledging the imperfect and incomplete relationship between antigen-stimulated DO11.10 TCR tg mice and HIV-infected humans, our data suggest that CD4+ T cell depletion in the setting of HIV disease may reflect, at least in part, chronic antigen exposure in the absence of proinflammatory signals and/or appropriate antigen-presenting cell functions. PMID:26416271

  12. Effects of T cell depletion in radiation bone marrow chimeras. III. Characterization of allogeneic bone marrow cell populations that increase allogeneic chimerism independently of graft-vs-host disease in mixed marrow recipients

    SciTech Connect

    Sykes, M.; Chester, C.H.; Sundt, T.M.; Romick, M.L.; Hoyles, K.A.; Sachs, D.H. )

    1989-12-01

    The opposing problems of graft-vs-host disease vs failure of alloengraftment severely limit the success of allogeneic bone marrow transplantation as a therapeutic modality. We have recently used a murine bone marrow transplantation model involving reconstitution of lethally irradiated mice with mixtures of allogeneic and syngeneic marrow to demonstrate that an allogeneic bone marrow subpopulation, removed by T cell depletion with rabbit anti-mouse brain serum and complement (RAMB/C), is capable of increasing levels of allogeneic chimerism. This effect was observed in an F1 into parent genetic combination lacking the potential for graft-vs-host disease, and radiation protection studies suggested that it was not due to depletion of stem cells by RAMB/C. We have now attempted to characterize the cell population responsible for increasing allogeneic chimerism in this model. The results indicate that neither mature T cells nor NK cells are responsible for this activity. However, an assay involving mixed marrow reconstitution in an Ly-5 congenic strain combination was found to be more sensitive to small degrees of stem cell depletion than radiation protection assays using three-fold titrations of bone marrow cells. Using this assay, we were able to detect some degree of stem cell depletion by treatment with RAMB/C, but not with anti-T cell mAb. Nevertheless, if the effects of alloresistance observed in this model are considered, the degree of stem cell depletion detected by such mixing studies in insufficient to account for the effects of RAMB/C depletion on levels of allogeneic chimerism, suggesting that another cell population with this property remains to be identified.

  13. The dark side of mast cell-targeted therapy in prostate cancer.

    PubMed

    Pittoni, Paola; Colombo, Mario Paolo

    2012-02-15

    Tumor development requires accomplices among white blood cells. Other than macrophages, mast cells have been observed to support the outgrowth of certain neoplasias because of their proangiogenic properties. In some tumor settings, however, mast cells may have a protective role, exerted by their proinflammatory mediators. In prostate cancer, no conclusive data on mast cell function were available. Here, we discuss recent work on the role of mast cells in mouse and human prostate cancer, showing that mast cells can behave alternatively as dangerous promoters, innocent bystanders, or essential guardians of tumors, according to the stage and origin of transformed cells. In particular, mast cells are essential for the outgrowth of early-stage tumors due to their matrix metalloproteinase-9 production, become dispensable in advanced-stage, post-epithelial-to-mesenchymal transition, and are protective against neuroendocrine prostate tumor variants. The common expression of c-Kit by mast cells and neuroendocrine clones suggests a possible competition for the ligand Stem cell factor and offers the chance of curing early-stage disease while preventing neuroendocrine tumors using c-Kit-targeted therapy. This review discusses the implications of these findings on the advocated mast cell-targeted cancer therapy and considers future directions in the study of mast cells and their interactions with other c-Kit-expressing cells. PMID:22307838

  14. Spacelab system analysis: A study of the Marshall Avionics System Testbed (MAST)

    NASA Technical Reports Server (NTRS)

    Ingels, Frank M.; Owens, John K.; Daniel, Steven P.; Ahmad, F.; Couvillion, W.

    1988-01-01

    An analysis of the Marshall Avionics Systems Testbed (MAST) communications requirements is presented. The average offered load for typical nodes is estimated. Suitable local area networks are determined.

  15. Neutrophil Recruitment by Tumor Necrosis Factor from Mast Cells in Immune Complex Peritonitis

    NASA Astrophysics Data System (ADS)

    Zhang, Yan; Ramos, Bernard F.; Jakschik, Barbara A.

    1992-12-01

    During generalized immune complex-induced inflammation of the peritoneal cavity, two peaks of tumor necrosis factor (TNF) were observed in the peritoneal exudate of normal mice. In mast cell-deficient mice, the first peak was undetected, and the second peak of TNF and neutrophil influx were significantly reduced. Antibody to TNF significantly inhibited neutrophil infiltration in normal but not in mast cell-deficient mice. Mast cell repletion of the latter normalized TNF, neutrophil mobilization, and the effect of the antibody to TNF. Thus, in vivo, mast cells produce the TNF that augments neutrophil emigration.

  16. Quercetin ameliorates paclitaxel-induced neuropathic pain by stabilizing mast cells, and subsequently blocking PKCε-dependent activation of TRPV1

    PubMed Central

    Gao, Wei; Zan, Yan; Wang, Zai-jie Jim; Hu, Xiao-yu; Huang, Fang

    2016-01-01

    Aim: Severe painful sensory neuropathy often occurs during paclitaxel chemotherapy. Since paclitaxel can activate mast cell and basophils, whereas quercetin, a polyphenolic flavonoid contained in various plants, which can specifically inhibit histamine release as a mast cell stabilizer. In this study we explore whether quercetin could ameliorate paclitaxel-induced neuropathic pain and elucidated the underlying mechanisms. Methods: Quercetin inhibition on histamine release was validated in vitro by detecting histamine release from rat basophilic leukemia (RBL-2H3) cells stimulated with paclitaxel (10 μmol/L). In the in vivo experiments, rats and mice received quercetin (20, 40 mg·kg-1·d-1) for 40 and 12 d, respectively. Meanwhile, the animals were injected with paclitaxel (2 mg/kg, ip) four times on d 1, 3, 5 and 7. Heat hyperalgesia and mechanical allodynia were evaluated at the different time points. The animals were euthanized and spinal cords and dorsal root ganglions were harvested for analyzing PKCε and TRPV1 expression levels. The plasma histamine levels were assessed in rats on d 31. Results: Pretreatment with quercetin (3, 10, 30 μmol/L) dose-dependently inhibited excessive histamine release from paclitaxel-stimulated RBL-2H3 cells in vitro, and quercetin administration significantly suppressed the high plasma histamine levels in paclitaxel-treated rats. Quercetin administration dose-dependently raised the thresholds for heat hyperalgesia and mechanical allodynia in paclitaxel-treated rats and mice. Furthermore, quercetin administration dose-dependently suppressed the increased expression levels of PKCε and TRPV1 in the spinal cords and DRGs of paclitaxel-treated rats and mice. Moreover, quercetin administration may inhibited the translocation of PKCε from the cytoplasm to the membrane in the spinal cord and DRG of paclitaxel-treated rats. Conclusion: Our results reveal the underlying mechanisms of paclitaxel-induced peripheral neuropathy and

  17. Hydroethanolic Pistacia atlantica hulls extract improved wound healing process; evidence for mast cells infiltration, angiogenesis and RNA stability.

    PubMed

    Farahpour, Mohammad Reza; Mirzakhani, Navideh; Doostmohammadi, Jamal; Ebrahimzadeh, Mahmood

    2015-05-01

    In Iranian traditional therapy folk, the Pistacia is used for treatment of wound inflammation. Here in the present study, the In vivo effect of Pistacia atlantica hulls ointment (PAO) on the wound healing process was assessed. Excision and incision wounds were induced in rats. Three different doses of PAO were administrated. Following 3, 7, 14 and 21 days, the tissue samples were obtained and skin irritation ratio, hydroxyproline content, as well as immune cells, fibroblasts, fibrocytes distribution and collagen density were analyzed. Moreover, the cellular RNA damage examined using epi-fluorescent microscope. Hydroethanolic extract of PAO significantly (P < 0.05) increased wound contraction percentage and up-regulated hydroxyproline content. The animals in medium and high dose PAO-treated groups exhibited remarkably (P < 0.05) higher fibroblast distribution and significantly (P < 0.05) lower immune cells infiltration. PAO up-regulated mast cells distribution on day 7 and elevated neovascularization in a dose dependent manner. Significantly lower RNA damage was revealed in PAO-treated animals. Our data showed that, PAO shortened the inflammation phase by provoking the fibroblast proliferation. Moreover, PAO enhanced mast cells distribution and infiltration, which in turn promoted the neovascularization. Ultimately, promoted angiogenesis increased RNA stability in different cell types. Thus, Hydroethanolic extract of PAO can be considered as an appropriate compound for wound healing medicine.

  18. Mast cells and histamine enhance the proliferation of non-small cell lung cancer cells.

    PubMed

    Stoyanov, Evgeniy; Uddin, Mohib; Mankuta, David; Dubinett, Steven M; Levi-Schaffer, Francesca

    2012-01-01

    Non-small cell lung cancer (NSCLC) is the most common form of lung cancer with an extremely low survival rate. It is characterized by a chronic inflammatory process with intense mast cell infiltrate that is associated with reduced survival. The aim of this study was to test the hypothesis that mast cells have an enhancing effect on NSCLC proliferation. To assess the tumor-promoting potential of mast cells, we used the human alveolar basal adenocarcinoma (A549) and the mouse Lewis lung carcinoma (LLC) cell lines, umbilical cord blood-derived mast cells (CBMC) and the mast cell-deficient mouse Sash model. The proliferation rate of A549/LLC cells was markedly increased by mast cells and histamine. Histamine proliferating activity was mediated via H(1), H(2) and H(4) receptors and caused ERK phosphorylation. LLC induced in Sash mice or in wild-type mice treated with the mast cell stabilizer nedocromil sodium displayed an accelerated growth (number of metastic colonies in the lungs, total lung area and lung/total mice weight ratio). In summary, we have shown a significant effect of mast cells and histamine in enhancing NSCLC/LLCX growth in vitro, while in a mouse LLC model in vivo we have found that mast cells are important negative regulators of cancer development. Therefore our results would indicate a pro-tumorogenic effect of the mast cells in vitro on established lung tumor cell lines, and anti-tumorogenic effect in mice at lung cancer induction. In conclusion, mast cell/anti-histamine targeted therapies should carefully consider this dual effect. PMID:21733595

  19. The STAT5-GATA2 Pathway Is Critical in Basophil and Mast Cell Differentiation and Maintenance

    PubMed Central

    Li, Yapeng; Qi, Xiaopeng; Liu, Bing; Huang, Hua

    2015-01-01

    Transcription factor GATA2 plays critical roles in hematopoietic stem cell survival and proliferation, GMP differentiation, and basophil and mast cell differentiation. However, precise roles of GATA2 in basophil and mast cell differentiation and maintenance have not been delineated. We have identified GATA2 as an essential transcription factor in differentiation of newly identified common basophil and mast cell progenitors into basophils and mast cells. We observed Gata2 haploinsufficiency for mast cell differentiation but not for basophil differentiation. We examined the precise role of GATA2 in maintaining the expression of a wide range of genes that are important for performing basophil or mast cell functions. The effects of GATA2 on gene expression were broadly based. We demonstrated that GATA2 was required for maintaining Fcer1a mRNA and FcεRIα protein expression on both basophils and mast cells as well as for maintaining Kit mRNA and c-Kit protein expression on mast cells. GATA2 was required for histamine synthesis and was also critical for Il4 mRNA expression in basophils and Il13 mRNA expression in mast cells. We demonstrate a STAT5-GATA2 connection, showing that the STAT5 transcription factor directly bound to the promoter and an intronic region of the Gata2 gene. Overexpression of the Gata2 gene was sufficient to direct basophil and mast cell differentiation in the absence of the Stat5 gene. Our study reveals that the STAT5-GATA2 pathway is critical for basophil and mast cell differentiation and maintenance. PMID:25801432

  20. Deciphering the unconventional peptide binding to the PDZ domain of MAST2.

    PubMed

    Delhommel, Florent; Chaffotte, Alain; Terrien, Elouan; Raynal, Bertrand; Buc, Henri; Delepierre, Muriel; Cordier, Florence; Wolff, Nicolas

    2015-07-01

    Phosphatase and tensin homologue (PTEN) and microtubule-associated serine threonine kinase 2 (MAST2) are key negative regulators of survival pathways in neuronal cells. The two proteins interact via the PDZ (PSD-95, Dlg1, Zo-1) domain of MAST2 (MAST2-PDZ). During infection by rabies virus, the viral glycoprotein competes with PTEN for interaction with MAST2-PDZ and promotes neuronal survival. The C-terminal PDZ-binding motifs (PBMs) of the two proteins bind similarly to MAST2-PDZ through an unconventional network of connectivity involving two anchor points. Combining stopped-flow fluorescence, analytical ultracentrifugation (AUC), microcalorimetry and NMR, we document the kinetics of interaction between endogenous and viral ligands to MAST2-PDZ as well as the dynamic and structural effects of these interactions. Viral and PTEN peptide interactions to MAST2-PDZ occur via a unique kinetic step which involves both canonical C-terminal PBM binding and N-terminal anchoring. Indirect effects induced by the PBM binding include modifications to the structure and dynamics of the PDZ dimerization surface which prevent MAST2-PDZ auto-association. Such an energetic communication between binding sites and distal surfaces in PDZ domains provides interesting clues for protein regulation overall. PMID:25942057

  1. Involvement of mast cells in inflammation induced by Trichomonas vaginalis via crosstalk with vaginal epithelial cells.

    PubMed

    Han, I H; Park, S J; Ahn, M H; Ryu, J S

    2012-01-01

    Vaginal epithelial cells (VECs) are thought to function as immune-responsive cells in trichomoniasis, and mast cells have been detected in vaginal smears and the vaginal wall in trichomoniasis. It therefore seemed possible that the VEC-trichomonad reaction might affect the activity of mast cells present in the lamina propria of the vaginal mucosa. In this study, we tested whether culture supernatants of VEC incubated with Trichomonas vaginalis (TCM) could stimulate mast cells. When VECs (MS74) were incubated with live trichomonads, IL-8, IL-6 and MCP-1 expressions increased in the TCM, and mast cells (HMC-1) and human neutrophils migrated more actively towards the TCM. Also, when the TCM was added to mast cells, β-hexosaminidase and cytokines (IL-8 and TNF-α) expressions were increased. Moreover, the culture supernatant of mast cells incubated with TCM (M-TCM) had more increased chemotactic activity for neutrophils than that of TCM. We conclude that inflammatory mediators made by VECs in response to activation by T. vaginalis activate and attract mast cells and then stimulate them to induce neutrophil migration. Our results indicate, for the first time, that VECs play a role in the infiltration of mast cells and neutrophils early in T. vaginalis infection. PMID:21981317

  2. 30 CFR 57.7051 - Loose objects on the mast or drill platform.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Loose objects on the mast or drill platform. 57... Drilling and Rotary Jet Piercing Drilling-Surface and Underground § 57.7051 Loose objects on the mast or drill platform. To prevent injury to personnel, tools and other objects shall not be left loose on...

  3. 30 CFR 57.7051 - Loose objects on the mast or drill platform.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Loose objects on the mast or drill platform. 57... Drilling and Rotary Jet Piercing Drilling-Surface and Underground § 57.7051 Loose objects on the mast or drill platform. To prevent injury to personnel, tools and other objects shall not be left loose on...

  4. Immunohistochemical Evaluation of Mast Cells in Leukoplakia and Oral Squamous Cell Carcinoma

    PubMed Central

    Narasimhan, Malathi

    2016-01-01

    Introduction More than 90% of oral cancers are squamous cell carcinomas with oral leukoplakia being the most common potentially malignant disorder. Among the cell types in the stroma, mast cells play an important role in tumourigenesis through various mechanisms. Aim The present study was aimed at comparing the mast cell count among normal oral mucosa, leukoplakia and Oral squamous cell carcinoma (OSSC) and to evaluate the possible role of mast cells in carcinogenesis. Materials and Methods Mast cell count was assessed immunohistochemically using anti-mast cell tryptase amongst 20 cases of leukoplakia and OSSC each and 10 normal gingival samples. Overall comparison was done using Kruskal Wallis test and intergroup comparison was done using Mann-Whitney U test. Results The results of the present study showed an increase in mast cell count from normal oral mucosa (Mean: 7.73) to leukoplakia (Mean: 15.11) to squamous cell carcinoma (Mean: 22.73). Comparison of mean number of mast cells amongst three groups (p-value: 0.001) and intergroup comparisons showed statistical significance. Conclusion Mast cells favour malignant transformation and can be used as indicators of disease progression. PMID:27656549

  5. Influence of Physicochemical Properties of Silver Nanoparticles on Mast Cell Activation and Degranulation

    PubMed Central

    Aldossari, Abdullah A.; Shannahan, Jonathan H.; Podila, Ramakrishna; Brown, Jared M.

    2014-01-01

    Silver nanoparticles (AgNPs) are increasingly being incorporated into products for their antimicrobial properties. This has resulted in increased human exposures and the possibility of adverse health effects. Mast cells orchestrate allergic immune responses through degranulation and release of pre-formed mediators. Little data exists on understanding interactions of AgNPs with mast cells and the properties that influence activation and degranulation. Using bone marrow-derived mast cells and AgNPs of varying physicochemical properties we tested the hypothesis that AgNP physicochemical properties influence mast cell degranulation and osteopontin production. AgNPs evaluated included spherical 20 nm and 110 nm suspended in either polyvinylpyrrolidone (PVP) or citrate, Ag plates suspended in PVP of diameters between 40–60 nm or 100–130 nm, and Ag nanowires suspended in PVP with thicknesses <100 nm and length up to 2 microns. Mast cell responses were found to be dependent on the physicochemical properties of the AgNP. Further, we determined a role for scavenger receptor B1 in AgNP-induced mast cell responses. Mast cell degranulation was not dependent on AgNP dissolution but was prevented by tyrosine kinsase inhibitor pretreatment. This study suggests that exposure to AgNPs may elicit adverse mast cell responses that could contribute to the initiation or exacerbation of allergic disease. PMID:25458489

  6. 52. VIEW FROM NORTH END OF SLC3W MAST TRENCH SHOWING ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    52. VIEW FROM NORTH END OF SLC-3W MAST TRENCH SHOWING NORTH FACE OF ERECT UMBILICAL MAST. LAUNCHER IN BACKGROUND. METEOROLOGICAL TOWER AND SLC-3E MST IN DISTANT BACKGROUND. - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 West, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

  7. Reversible expansion of primate mast cell populations in vivo by stem cell factor.

    PubMed Central

    Galli, S J; Iemura, A; Garlick, D S; Gamba-Vitalo, C; Zsebo, K M; Andrews, R G

    1993-01-01

    Mast cell development in mice is critically regulated by stem cell factor (SCF), the term used here to designate a product of fibroblasts and other cell types that is a ligand for the tyrosine kinase receptor protein encoded by the proto-oncogene c-kit. However, the factors which regulate the size of mast cell populations in primates are poorly understood. Here we report that the subcutaneous administration of recombinant human SCF (rhSCF) to baboons (Papio cynocephalus) or cynomolgus monkeys (Macaca fascicularis) produced a striking expansion of mast cell populations in many anatomical sites, with numbers of mast cells in some organs of rhSCF-treated monkeys exceeding the corresponding values in control monkeys by more than 100-fold. Animals treated with rhSCF did not exhibit clinical evidence of mast cell activation, and discontinuation of treatment with rhSCF resulted in a rapid decline of mast cell numbers nearly to baseline levels. These findings are the first to demonstrate that a specific cytokine can regulate mast cell development in primates in vivo. They also provide the first evidence, in any mammalian species, to indicate that the cytokine-dependent expansion of tissue mast cell populations can be reversed when administration of the cytokine is discontinued. Images PMID:7678600

  8. Mast Cells and Irritable Bowel Syndrome: From the Bench to the Bedside

    PubMed Central

    Zhang, Lei; Song, Jun; Hou, Xiaohua

    2016-01-01

    Irritable bowel syndrome (IBS) is traditionally defined as a functional disorder since it lacks demonstrable pathological abnormalities. However, in recent years, low grade inflammatory infiltration, often rich in mast cells, in both the small and large bowel, has been observed in some patients with IBS. The close association of mast cells with major intestinal functions, such as epithelial secretion and permeability, neuroimmune interactions, visceral sensation, and peristalsis, makes researchers and gastroenterologists to focus attention on the key roles of mast cells in the pathogenesis of IBS. Numerous studies have been carried out to identify the mechanisms in the development, infiltration, activation, and degranulation of intestinal mast cells, as well as the actions of mast cells in the processes of mucosal barrier disruption, mucosal immune dysregulation, visceral hypersensitivity, dysmotility, and local and central stress in IBS. Moreover, therapies targeting mast cells, such as mast cell stabilizers (cromoglycate and ketotifen) and antagonists of histamine and serotonin receptors, have been tried in IBS patients, and have partially exhibited considerable efficacy. This review focuses on recent advances in the role of mast cells in IBS, with particular emphasis on bridging experimental data with clinical therapeutics for IBS patients. PMID:26755686

  9. Mast cell-derived neurotrophin 4 mediates allergen-induced airway hyperinnervation in early life

    PubMed Central

    Patel, Kruti R.; Aven, Linh; Shao, Fengzhi; Krishnamoorthy, Nandini; Duvall, Melody G.; Levy, Bruce D.; Ai, Xingbin

    2016-01-01

    Asthma often progresses from early episodes of insults. How early life events connect to long-term airway dysfunction remains poorly understood. We demonstrated previously that increased neurotrophin 4 (NT4) levels following early life allergen exposure cause persistent changes in airway smooth muscle (ASM) innervation and airway hyper-reactivity (AHR) in mice. Herein, we identify pulmonary mast cells as a key source of aberrant NT4 expression following early insults. NT4 is selectively expressed by ASM and mast cells in mice, nonhuman primates and humans. We show in mice that mast cell-derived NT4 is dispensable for ASM innervation during development. However, upon insults, mast cells expand in number and degranulate to release NT4 and thus become the major source of NT4 under pathological condition. Adoptive transfer of wild type mast cells, but not NT4−/− mast cells restores ASM hyperinnervation and AHR in KitW-sh/W-sh mice following early life insults. Notably, an infant nonhuman primate model of asthma also exhibits ASM hyperinnervation associated with the expansion and degranulation of mast cells. Together, these findings identify an essential role of mast cells in mediating ASM hyperinnervation following early life insults by producing NT4. This role may be evolutionarily conserved in linking early insults to long-term airway dysfunction. PMID:26860818

  10. In vitro inhibition of human conjunctival mast-cell degranulation by ketotifen.

    PubMed

    Schoch, C

    2003-02-01

    Ketotifen relieves the symptoms of allergic conjunctivitis through multiple mechanisms of action. One such mechanism may involve stabilization of conjunctival mast cells. Because of inter- and intra-species variation, however, this hypothesis cannot be adequately tested using mast cells from animals or other human tissues. We therefore employed human conjunctival mast cells. The mast cells were prepared using human conjunctival tissues obtained from US eye banks. Cell suspensions were sensitized with human IgE and incubated with ketotifen fumarate or control. After antigenic challenge of sensitized cells with anti-IgE, levels of histamine and tryptase, two mast-cell granule markers, were measured in the supernatant fluid. Cell viability was assessed with a Trypan Blue assay. Ketotifen at concentrations of approximately 10(-11) to 10(-4) M inhibited mast-cell histamine release by 90% or more. Similarly, ketotifen at approximately 10(-10) to 10(-4) M inhibited tryptase release by 90% or more (apart from a single anomalous reading). At all ketotifen concentrations that stabilized mast cells, cell viability was preserved. Moreover, ketotifen did not impair cell viability unless concentrations were increased above the clinically relevant range, i.e., above the order of magnitude of 10(-4) M. These data demonstrate that ketotifen can stabilize human conjunctival mast cells, without impairing cell viability.

  11. [The effect of a mite allergen on Na/H metabolic activity in peritoneal mast cells].

    PubMed

    Khlgatian, S V; Pinelis, V G; Berzhets, V M; Strukova, S M

    1992-12-01

    Mite allergen interacting with mast cells treated with sera from bronchial patient sensitized to home dust Dermatophagoides farinae causes changes in intracellular pH. Regulation of pHi peritoneal mast cells is participated by Na/H metabolism probably activated by protein kinase C.

  12. Effect of sulfur mustard on mast cells in hairless guinea pig skin

    SciTech Connect

    Graham, J.S.; Bryant, M.A.; Braue, E.H.

    1993-05-13

    The skin of 24 anesthetized hairless guinea pigs was exposed to saturated sulfur mustard (bis-2-chloroethyl sulfide; HD) for 5 and 7 minutes using 14-mm diameter vapor cups. Animals were euthanatized 24 hours after exposure and skin specimens taken for morphometric evaluation of granulated mast cells with an image analysis system (IAS). Tissue specimens were processed in paraffin, sectioned at 5 microns and stained with Unna's stain for mast cells. The number of granulated mast cells and the area occupied by mast cell granules was determined. There were significantly fewer mast cells (p < 0.05) in either HD exposure group than in sham-exposed animals, with significantly fewer mast cells in the 7-minute than the 5-minute HD group. There were also significantly smaller areas occupied by granules in either HD exposure group than in sham-exposed animals. HD-induced lesions in the hairless guinea pig have shown signs of an inflammatory response, and with their granules of vasoactive histamine, mast cells might be expected to play a role in HD-induced injury. Changes in mast cells exposed to low sulfur mustard levels, as detected by an IAS, may serve as an early marker for cutaneous damage, which might not be as easily determined with routine light microscopy.

  13. MAST 1 purchased products--components. Final report

    SciTech Connect

    Brown, R.J.

    1995-10-01

    AlliedSignal Inc., Kansas City Division, the production agency, was provided with funding to acquire purchased product components in support of the MAST (Multi-Application Surety Technology) Program. Implementation efforts, closing procurement status, and proposals for improvements in the procurement process are presented. The intent of this project was to fund the Purchased Product Team`s traditional procurement of components, with significantly reduced flowtime, in accordance with the Qualification Evaluation System, and to exercise the system to the extent possible. When funding was reduced, it became obvious that full implementation of the Qualification Evaluation System could not be achieved due to limited resources.

  14. 2D/3D Visual Tracker for Rover Mast

    NASA Technical Reports Server (NTRS)

    Bajracharya, Max; Madison, Richard W.; Nesnas, Issa A.; Bandari, Esfandiar; Kunz, Clayton; Deans, Matt; Bualat, Maria

    2006-01-01

    A visual-tracker computer program controls an articulated mast on a Mars rover to keep a designated feature (a target) in view while the rover drives toward the target, avoiding obstacles. Several prior visual-tracker programs have been tested on rover platforms; most require very small and well-estimated motion between consecutive image frames a requirement that is not realistic for a rover on rough terrain. The present visual-tracker program is designed to handle large image motions that lead to significant changes in feature geometry and photometry between frames. When a point is selected in one of the images acquired from stereoscopic cameras on the mast, a stereo triangulation algorithm computes a three-dimensional (3D) location for the target. As the rover moves, its body-mounted cameras feed images to a visual-odometry algorithm, which tracks two-dimensional (2D) corner features and computes their old and new 3D locations. The algorithm rejects points, the 3D motions of which are inconsistent with a rigid-world constraint, and then computes the apparent change in the rover pose (i.e., translation and rotation). The mast pan and tilt angles needed to keep the target centered in the field-of-view of the cameras (thereby minimizing the area over which the 2D-tracking algorithm must operate) are computed from the estimated change in the rover pose, the 3D position of the target feature, and a model of kinematics of the mast. If the motion between the consecutive frames is still large (i.e., 3D tracking was unsuccessful), an adaptive view-based matching technique is applied to the new image. This technique uses correlation-based template matching, in which a feature template is scaled by the ratio between the depth in the original template and the depth of pixels in the new image. This is repeated over the entire search window and the best correlation results indicate the appropriate match. The program could be a core for building application programs for systems

  15. New GALEX UV Data Products At MAST For Stellar Astrophysics

    NASA Astrophysics Data System (ADS)

    Shiao, Bernie; Fleming, S. W.; Million, C.; Seibert, M.; Bianchi, L.; Thompson, R.; Tseng, S.; Adler, W. J.; Hubbard, M.; Levay, K.; Madore, B. F.; Martin, C. D.; Nieto-Santisteban, M. A.; Sahai, R.; Schiminovich, D.; White, R. L.; Wyder, T. K.

    2014-01-01

    The Galaxy Evolution Explorer (GALEX) mission ended in June 2013 after ten years in orbit. Its FUV and NUV microchannel plate detectors were used to conduct a variety of direct imaging and spectroscopic astronomical surveys with various depths and sky coverage, recording individual photon events with a time resolution of five thousandths of a second. Although the mission has ended, MAST is continuing to provide new data products as the mission transitions to a legacy archive. One product is the GCAT (Seibert et al., in prep), a catalog of GALEX sources across the entire GR6 data release that removes duplicate objects found in the GALEX MCAT. The GCAT defines "primary" NUV and FUV fluxes within the AIS and MIS surveys 40 million and 22 million sources, respectively), accounting for tile overlaps, and with visual inspection of every tile to flag artifacts and conduct other quality control checks. Another catalog of unique sources is that of Bianchi et al. (2013). Similar to the GCAT, their catalog produces a list of distinct GALEX sources in both the FUV and NUV from the AIS and MIS surveys, and includes data from GR7 (through the end of 2012). They have also cross-matched their sources with SDSS DR9, GSC-II, PanSTARRS, and 2MASS. We review access options for these catalogs, including updated matches between the GCAT and SDSS / Kepler available at MAST. In addition to these unique GALEX source catalogs, MAST will provide a database and software package that archives each of the ~1.5 trillion photon events detected over the lifetime of the mission. For the first time, users will be able to create calibrated lightcurves, intensity maps, and animated movies from any set of photons selected across any tile, and with specified aperture sizes, coordinates, and time steps. Users can access the data using either a python-based command-line software package, through a web interface at MAST, or (eventually) through CasJobs using direct SQL queries. We present some example

  16. Mast cell gastritis: Children complaining of chronic abdominal pain with histologically normal gastric mucosal biopsies except for increase in mast cells, proposing a new entity

    PubMed Central

    Mahjoub, Fatemeh E; Farahmand, Fatemeh; Pourpak, Zahra; Asefi, Hoda; Amini, Zahra

    2009-01-01

    Background Mast cells reside within the connective tissue of a variety of tissues and all vascularized organs. Since 1996, few studies have been performed on mast cell density in gastrointestinal biopsies, mainly in adult age group. We recently studied mast cell density in pediatric age group on rather larger number of cases in a referral children hospital. Mast cell density was 12.6 ± 0.87 in 0.25 mm2 (range: 0-81) in our study. Since we frequently encounter cases with rather normal gastric biopsies with no H.pylori, which mainly complain of chronic abdominal pain, we gathered those cases with mast cell density more than 30/0.25 mm2. from 895 gastric biopsies and wanted to study their clinical and endoscopic findings and propose a new entity. Methods Between April 2005 and May 2008, 895 children (< 14 years old), with gastrointestinal complaints who underwent endoscopy were selected and antral biopsies were obtained for histological examination. Among these children, those who had normal or erythematous (but not nodular or ulcerative) gastric mucosa on endoscopic view, plus pathologic report of normal mucosa or mild gastritis in addition to mast cell count more than 30/25 mm2, were chosen and a questionnaire was filled for each patient including clinical, endoscopic and pathologic findings. The statistical analysis was performed using SPSS, version 13 (SPSS Inc., Chicago, IL, USA). Results Over a 3 year period of study, of 895 selected children, 86 patients fulfilled the entrance criteria. The major complaint of patients was recurrent abdominal pain. The mean mast cell density was 45.59 ± 13.81 in 0.25 mm2 (range: 30-93). Among our cases, about 67.4% (n = 58) had 30 to 49, 23.3% (n = 20) had 50 to 69, 8.1% (n = 7) had 70 to 89 and 1.2% (n = 1) had 93 mast cells/0.25 mm2 in their specimens Discussion In 29% of our cases, neither endoscopic nor pathologic change was detected and only increase in mast cell number was reported and in others endoscopic and

  17. Mast cell-deficient W-sash c-kit mutant Kit W-sh/W-sh mice as a model for investigating mast cell biology in vivo.

    PubMed

    Grimbaldeston, Michele A; Chen, Ching-Cheng; Piliponsky, Adrian M; Tsai, Mindy; Tam, See-Ying; Galli, Stephen J

    2005-09-01

    Mice carrying certain mutations in the white spotting (W) locus (ie, c-kit) exhibit reduced c-kit tyrosine kinase-dependent signaling that results in mast cell deficiency and other phenotypic abnormalities. The c-kit mutations in Kit(W/W-v) mice impair melanogenesis and result in anemia, sterility, and markedly reduced levels of tissue mast cells. In contrast, Kit(W-sh/W-sh) mice, bearing the W-sash (W(sh)) inversion mutation, have mast cell deficiency but lack anemia and sterility. We report that adult Kit(W-sh/W-sh) mice had a profound deficiency in mast cells in all tissues examined but normal levels of major classes of other differentiated hematopoietic and lymphoid cells. Unlike Kit(W/W-v) mice, Kit(W-sh/W-sh) mice had normal numbers of TCR gammadelta intraepithelial lymphocytes in the intestines and did not exhibit a high incidence of idiopathic dermatitis, ulcers, or squamous papillomas of the stomach, but like Kit(W/W-v) mice, they lacked interstitial cells of Cajal in the gut and exhibited bile reflux into the stomach. Systemic or local reconstitution of mast cell populations was achieved in nonirradiated adult Kit(W-sh/W-sh) mice by intravenous, intraperitoneal, or intradermal injection of wild-type bone marrow-derived cultured mast cells but not by transplantation of wild-type bone marrow cells. Thus, Kit(W-sh/W-sh) mice represent a useful model for mast cell research, especially for analyzing mast cell function in vivo. PMID:16127161

  18. Application of cultured human mast cells (CHMC) for the design and structure-activity relationship of IgE-mediated mast cell activation inhibitors.

    PubMed

    Argade, Ankush; Bhamidipati, Somasekhar; Li, Hui; Carroll, David; Clough, Jeffrey; Keim, Holger; Sylvain, Catherine; Rossi, Alexander B; Coquilla, Christina; Issakani, Sarkiz D; Masuda, Esteban S; Payan, Donald G; Singh, Rajinder

    2015-01-01

    Here we report the optimization of small molecule inhibitors of human mast cell degranulation via anti-IgE-mediated tryptase release following cross-linking and activation of IgE-loaded FcεR1 receptors. The compounds are selective upstream inhibitors of FcεR1-dependent human mast cell degranulation and proved to be devoid of activity in downstream ionomycin mediated degranulation. Structure-activity relationship (SAR) leading to compound 26 is outlined.

  19. Influence of mass moment of inertia on normal modes of preloaded solar array mast

    NASA Technical Reports Server (NTRS)

    Armand, Sasan C.; Lin, Paul

    1992-01-01

    Earth-orbiting spacecraft often contain solar arrays or antennas supported by a preloaded mast. Because of weight and cost considerations, the structures supporting the spacecraft appendages are extremely light and flexible; therefore, it is vital to investigate the influence of all physical and structural parameters that may influence the dynamic behavior of the overall structure. The study primarily focuses on the mast for the space station solar arrays, but the formulations and the techniques developed in this study apply to any large and flexible mast in zero gravity. Furthermore, to determine the influence on the circular frequencies, the mass moment of inertia of the mast was incorporated into the governing equation of motion for bending. A finite element technique (MSC/NASTRAN) was used to verify the formulation. Results indicate that when the mast is relatively flexible and long, the mass moment inertia influences the circular frequencies.

  20. Immunoreactivity for CD25 in gastrointestinal mucosal mast cells is specific for systemic mastocytosis.

    PubMed

    Hahn, Hejin P; Hornick, Jason L

    2007-11-01

    Systemic mastocytosis (SM) is characterized by the accumulation of neoplastic mast cells in bone marrow and other organs. Gastrointestinal (GI) symptoms are common in both SM and cutaneous mastocytosis [urticaria pigmentosa (UP)], and are usually caused by the release of histamine and other inflammatory mediators. Occasionally, neoplastic mast cells may also directly infiltrate the GI tract. Previous studies have suggested that enumeration of the mast cells in GI biopsies may help establish the diagnosis of SM. However, mast cells have been reported to be increased in various inflammatory diseases, and mast cell density has not been systematically evaluated in other GI disorders. Recently, expression of CD25 by mast cells in bone marrow has been shown to be specific for SM. The purpose of this study was (1) to quantitate and compare mast cells in mucosal biopsies from patients with SM involving the GI tract, UP with GI symptoms, and a control group of diverse inflammatory disorders, and (2) to determine whether immunostaining for CD25 can be used to distinguish neoplastic from reactive mast cells in GI biopsies. Seventeen GI biopsies from 6 patients with SM; 17 GI biopsies from 5 patients with UP; and 157 control cases including 10 each normal stomach, duodenum, terminal ileum, and colon, Helicobacter pylori gastritis, bile reflux gastropathy, peptic duodenitis, celiac disease, Crohn disease, ulcerative colitis, lymphocytic colitis, and collagenous colitis, 20 biopsies from 16 patients with irritable bowel syndrome, 8 biopsies from 5 patients with parasitic infections, and 9 biopsies from 7 patients with eosinophilic gastroenteritis were immunostained for mast cell tryptase, c-kit (CD117), and CD25. Mucosal mast cells were quantitated, and the presence or absence of CD25 expression on mast cells was determined. In SM patients, mast cells in the small intestine and colon numbered >100/high-power field (HPF) in nearly all cases (mean 196/HPF; range 74 to 339). This

  1. Characteristics of mast cells in normal bladder, bacterial cystitis and interstitial cystitis.

    PubMed

    Christmas, T J; Rode, J

    1991-11-01

    An analysis was made of the numbers and characteristics of mast cells in lateral bladder wall biopsies from 22 patients with interstitial cystitis, 6 with bacterial cystitis and 8 normal controls, using toluidine blue stains and computerised video image analysis techniques. A significantly greater number of mast cells were found within the detrusor muscle in interstitial cystitis than in bacterial cystitis or normal controls. Within the urothelium and submucosa, mast cell numbers were significantly greater than in normal controls in both interstitial and bacterial cystitis. In interstitial cystitis mast cells were significantly larger within the detrusor than in the urothelium/submucosa and they appeared to degranulate predominantly within the superficial layers. Differential staining techniques, using long and short toluidine blue stains, failed to reveal statistically significant evidence of mast cell heterogeneity within the bladder wall in interstitial cystitis.

  2. Engineered Nanostructures of Antigen Provide an Effective Means for Regulating Mast Cell Activation

    PubMed Central

    Deng, Zhao; Weng, I-Chun; Li, Jie-Ren; Chen, Huan-Yuan; Liu, Fu-Tong; Liu, Gang-yu

    2011-01-01

    Nanostructures containing 2,4-Dinitrophenyl (DNP) as antigen were designed and produced to investigate antibody-mediated activation of mast cells. The design consists of nanogrids of DNP termini inlaid in alkanethiol self-assembled monolayers (SAMs). Using scanning probe-based nanografting, nanometer precision was attained for designed geometry, size and periodicity. Rat basophilic leukemia (RBL) cells exhibited high sensitivity to the geometry and local environment of DNP presented on these nanostructures. The impact included cellular adherence, spreading, membrane morphology, cytoskeleton structure, and activation. The highest level of spreading and activation was induced by nanogrids of 17 nm line width and 40 nm periodicity, with DNP haptens 1.4 nm above the surroundings. The high efficacy is attributed to two main factors. First, DNP sites in the nanostructure are highly accessible by anti-DNP-IgE during recognition. Second, the arrangement or geometry of DNP termini in nanostructures promotes clustering of FcεRI receptors that are pre-linked to IgE. The clustering effectively initiates Lyn-mediated signaling cascades, ultimately leading to the degranulation of RBL cells. This work demonstrates an important concept, that nanostructures of ligands provide new and effective cues for directing cellular signaling processes. PMID:21999491

  3. Evolution of intracerebral hemorrhage after intravenous tPA: reversal of harmful effects with mast cell stabilization

    PubMed Central

    Marinkovic, Ivan; Mattila, Olli S; Strbian, Daniel; Meretoja, Atte; Shekhar, Shashank; Saksi, Jani; Abo-Ramadan, Usama; Rantanen, Ville; Lindsberg, Perttu J; Tatlisumak, Turgut

    2014-01-01

    Thrombolysis with tissue plasminogen activator (tPA) traditionally demands baseline imaging to rule out intracerebral hemorrhage (ICH), which causes delays in treatment. Preventing possible adverse effects of tPA on ICH would allow rapid on-site thrombolysis in patients with presumed acute ischemic stroke, reducing onset-to-treatment times. We examined how intravenous tPA alters ICH evolution during an extended follow-up, and how mast cell stabilization affects this process. Intracerebral hemorrhage was induced in rats by collagenase injection. Rats received either saline (n=10), tPA (n=13), tPA+low-dose cromoglycate (n=10), or tPA+high-dose cromoglycate (n=10). Magnetic resonance imaging was performed at 24, 48, and 72 hours after ICH induction, together with neurologic evaluations. During 72 hours of follow-up, tPA administration did not significantly increase hematoma volume (mean±s.d. 83.5±14.3 versus 66.7±14.7 μL; P=0.256) or hemispheric expansion (14.5±5.0 versus 11.5±5.0% P=0.457) compared with saline. However, tPA-treated animals had worse neurologic outcomes (P<0.05), and mortality (8/13 versus 3/10). Combining tPA with high-dose cromoglycate mitigated hemispheric expansion (7.4±1.7 versus 14.5±5.0% P=0.01), improved neurologic outcome (P<0.001) and decreased mortality (1/10; P<0.05) compared with tPA alone. Our results suggest tPA increases neurologic deficit in ICH, an effect that was abolished by concomitant mast cell stabilization. Further studies are needed to establish the clinical relevance of these findings. PMID:24169849

  4. Isolation of Mature (Peritoneum-Derived) Mast Cells and Immature (Bone Marrow-Derived) Mast Cell Precursors from Mice

    PubMed Central

    Meurer, Steffen K.; Neß, Melanie; Weiskirchen, Sabine; Kim, Philipp; Tag, Carmen G.; Kauffmann, Marlies; Huber, Michael; Weiskirchen, Ralf

    2016-01-01

    Mast cells (MCs) are a versatile cell type playing key roles in tissue morphogenesis and host defence against bacteria and parasites. Furthermore, they can enhance immunological danger signals and are implicated in inflammatory disorders like fibrosis. This granulated cell type originates from the myeloid lineage and has similarities to basophilic granulocytes, both containing large quantities of histamine and heparin. Immature murine mast cells mature in their destination tissue and adopt either the connective tissue (CTMC) or mucosal (MMC) type. Some effector functions are executed by activation/degranulation of MCs which lead to secretion of a typical set of MC proteases (MCPT) and of the preformed or newly synthesized mediators from its granules into the local microenvironment. Due to the potential accumulation of mutations in key signalling pathway components of corresponding MC cell-lines, primary cultured MCs are an attractive mean to study general features of MC biology and aspects of MC functions relevant to human disease. Here, we describe a simple protocol for the simultaneous isolation of mature CTMC-like murine MCs from the peritoneum (PMCs) and immature MC precursors from the bone marrow (BM). The latter are differentiated in vitro to yield BM-derived MCs (BMMC). These cells display the typical morphological and phenotypic features of MCs, express the typical MC surface markers, and can be propagated and kept in culture for several weeks. The provided protocol allows simple amplification of large quantities of homogenous, non-transformed MCs from the peritoneum and bone marrow-derived mast cells for cell- and tissue-based biomedical research. PMID:27337047

  5. 3T3 fibroblasts induce cloned interleukin 3-dependent mouse mast cells to resemble connective tissue mast cells in granular constituency

    SciTech Connect

    Dayton, E.T.; Pharr, P.; Ogawa, M.; Serafin, W.E.; Austen, K.F.; Levi-Schaffer, F.; Stevens, R.L.

    1988-01-01

    As assessed by ultrastructure, histochemical staining, and T-cell dependency, in vitro-differentiated interleukin 3-dependent mouse mast cells are comparable to the mast cells that reside in the gastrointestinal mucosa but not in the skin or the serosal cavity of the mouse. The authors now demonstrate that when cloned interleukin 3-dependent mast cells are cocultured with mouse skin-derived 3T3 fibroblasts in the presence of WEHI-3 conditioned medium for 28 days, the mast cells acquire the ability to stain with safranin, increase their histamine content approx. 50-fold and their carboxypeptidase. A content approx. 100-fold, and augment approx. their biosynthesis of proteoglycans bearing /sup 35/S-labeled haparin relative to /sup 35/S-labeled chondroitin sulfate glycosaminoglycans. Thus, fibroblasts induce interleukin 3-dependent mouse mast cells to change phenotype from mucosal-like to connective tissue-like, indicating that the biochemical and functional characteristics of this mast cell type are strongly influenced by the connective tissue microenvironment.

  6. Nitrogen storage dynamics are affected by masting events in Fagus crenata.

    PubMed

    Han, Qingmin; Kabeya, Daisuke; Iio, Atsuhiro; Inagaki, Yoshiyuki; Kakubari, Yoshitaka

    2014-03-01

    It is generally assumed that the production of a large crop of seeds depletes stores of resources and that these take more than 1 year to replenish; this is accepted, theoretically, as the proximate mechanism of mast seeding (resource budget model). However, direct evidence of resource depletion in masting trees is very rare. Here, we trace seasonal and inter-annual variations in nitrogen (N) concentration and estimate the N storage pool of individuals after full masting of Fagus crenata in two stands. In 2005, a full masting year, the amount of N in fruit litter represented half of the N present in mature leaves in an old stand (age 190-260 years), and was about equivalent to the amount of N in mature leaves in a younger stand (age 83-84 years). Due to this additional burden, both tissue N concentration and individual N storage decreased in 2006; this was followed by significant replenishment in 2007, although a substantial N store remained even after full masting. These results indicate that internal storage may be important and that N may be the limiting factor for fruiting. In the 4 years following full masting, the old stand experienced two moderate masting events separated by 2 years, whilst trees in the younger stand did not fruit. This different fruiting behavior may be related to different "costs of reproduction" in the full masting year 2005, thus providing more evidence that N may limit fruiting. Compared to the non-fruiting stand, individuals in the fruiting stand exhibited an additional increase in N concentrations in roots early in the 2007 growing season, suggesting additional N uptake from the soil to supply resource demand. The enhanced uptake may alleviate the N storage depletion observed in the full masting year. This study suggests that masting affects N cycle dynamics in mature Fagus crenata and N may be one factor limiting fruiting. PMID:24221082

  7. Exposure to tobacco-derived materials induces overproduction of secreted proteinases in mast cells

    SciTech Connect

    Small-Howard, Andrea; Turner, Helen . E-mail: hturner@queens.org

    2005-04-15

    Mast cells reside at interfaces with the environment, including the mucosa of the respiratory and gastrointestinal tracts. This localization exposes mast cells to inhaled, or ingested, environmental challenges. In the airways of smokers, resident immune cells will be in contact with the condensed components of cigarette smoke. Mast cells are of particular interest due to their ability to promote airway remodeling and mucus hypersecretion. Clinical data show increased levels of mast cell-secreted tryptase and increased numbers of degranulated mast cells in the lavage and bronchial tissue of smokers. Since mast cell-secreted proteinases (MCPTs), including tryptases, contribute to pathological airway remodeling, we investigated the relationship between mast cell proteinases and smoke exposure. We exposed a mast cell line to cigarette smoke condensate (CSC). We show that CSC exposure increases MCPT levels in mast cells using an assay for tryptase-type MCPT activity. We hypothesized that this increase in MCPT activity reflects a CSC-induced increase in the cytosolic pool of proteinase molecules, via stimulation of MCPT transcription. Transcript array data suggested that mRNA changes in response to CSC were limited in number and peaked after 3 h of CSC exposure. However, we noted marked transcriptional regulation of several MCPT genes. CSC-induced changes in the mRNA levels for MCPTs were confirmed using quantitative RT-PCR. Taken together, our data suggest that chronic exposure to cigarette smoke up-regulates MCPT levels in mast cells at both the protein and the mRNA level. We suggest that the pathological airway remodeling that has been described in clinical studies of smoke inhalation may be attributable to MCPT overproduction in vivo.

  8. Mast cells, disease and gastrointestinal cancer: A comprehensive review of recent findings

    PubMed Central

    Hodges, Kyle; Kennedy, Lindsey; Meng, Fanyin; Alpini, Gianfranco; Francis, Heather

    2012-01-01

    Paul Ehrlich, a German scientist, discovered what is known as the mast cell in the late 1800’s, which has proven to be an important player in the immune system of vertebrates. Mast cells are ubiquitous throughout the tissues of the human body and play numerous roles, both beneficial and destructive. We know they are important in our army of immunity warrior cells, which defend us against viruses, bacteria and parasitic invaders. They are also very well known for the havoc they wreak, causing uncomfortable symptoms due to their release of histamine and other mediators which cause the all too familiar itching, sneezing, urticaria and rhinorrhea of allergic responses. Mast cell activities are diverse and include painful inflammatory reactions in autoimmune conditions such as rheumatoid arthritis. In the gastrointestinal system, mast cells are implicated in diverse actions such as increased gastric acid secretion, polyp formation and uncomfortable conditions such as Irritable Bowel Syndrome. The role of immunology and mast cells in these areas is intriguing but less well understood than their role in allergic responses. Because mast cells have been implicated in both physiologic as well as pathogenic processes, they have been the subjects of avid study. Review of the current literature on mast cell biology reveals that there are many studies of their presence within the tumor microenvironment and evidence, which supports mast cell influence on tumor angiogenesis, tumor invasion, and immune suppression. The studies reviewed in this article concentrate largely on mast cells in human GI malignancies. This review also provides background information regarding mast cells, such as their origination, their location within the body, how they are activated and how they function as mediators. PMID:22943044

  9. Extracellular matrix-anchored serum amyloid A preferentially induces mast cell adhesion.

    PubMed

    Hershkoviz, R; Preciado-Patt, L; Lider, O; Fridkin, M; Dastych, J; Metcalfe, D D; Mekori, Y A

    1997-07-01

    Mast cells are known to accumulate in various inflammatory processes, some of which are known to be associated with increased local and systemic levels of acute-phase reactants such as serum amyloid A (SAA) or with amyloid deposition. The mechanism(s) by which mast cells are recruited to these sites, however, has not been fully elucidated. It has recently been shown that SAA interacts with extracellular matrix (ECM) components and thereby acts as a chemoattractant and regulator of immune cell migration. On the basis of these observations, we examined the effect of SAA on mast cell adhesion to ECM, an essential step in cellular transmigration. We could first demonstrate strong specific binding of recombinant human SAA (rSAA) to murine mast cells using flow cytometry. Moreover, radiolabeled rSAA was found to bind, in a saturable manner, to mast cells, reaching a binding affinity of 10(-8) M. When immobilized by preincubation with ECM, SAA or its proteolytically degraded amyloid A fragment (amino acid residues 2-82), which contains RGD-related adhesion motif but not the COOH-terminal portion of SAA (amino acid residues 77-104), induced the adhesion of resting mast cells to ECM or laminin. SAA and AA, in soluble or immobilized forms, did not activate mast cells to release mediators. Mast cell adhesion to the immobilized ECM-SAA complex appeared to occur through an integrin recognition, inasmuch as adhesion was calcium dependent and could be blocked by an RGD-containing peptide or by anti-CD29 monoclonal antibody. Genistein also inhibited adhesion, indicating that tyrosine kinase activity was involved. These data suggest that SAA bound to ECM may serve as an important inducer of mast cell adhesion, thus regulating mast cell recruitment and accumulation at these sites, which in turn could potentiate further pathology. PMID:9252455

  10. Functional heterogeneity of mast cells isolated from different microenvironments within nasal polyp tissue.

    PubMed Central

    Finotto, S; Dolovich, J; Denburg, J A; Jordana, M; Marshall, J S

    1994-01-01

    Nasal polyposis is a chronic inflammatory condition of the upper airways characterized by infiltration of activated inflammatory cells, including mast cells, both in the epithelium and in the stroma. The aim of this work was to study human mast cells derived from two different anatomical sites within the same nasal polyp tissue. To this end, we isolated two distinct mast cell populations, one from the epithelial and the other from the stromal layers of individual human nasal polyp tissues. We examined the mediator content of the two mast cell populations and found that stromal mast cells had a significantly higher content of tryptase compared with the epithelial mast cells from the same tissue. In addition, mast cells from the stromal compartment, but not those from the epithelium, released a significant amount of histamine after anti-IgE stimulation. By contrast, both populations released over 50% of the total histamine after non-specific stimuli (A23187 10(-6) M). The content of mediators and the response to immunological activation were not significantly altered in patients receiving topical steroid therapy. It remains to be determined if the observed differences are the result of an intrinsic characteristic of the mast cell populations localized to separate tissue compartments, or reflect a different in vivo exposure to stimuli such as antigens, or different surrounding structural or infiltrating cells. In conclusion, these data provide evidence of functional heterogeneity and differences in mediator content between mast cell subpopulations from a single human tissue. The failure of release of epithelial mast cell mediators from an immunologic stimulus may have implications concerning acute effects of antigen exposure in nasal polyposis. Images Fig. 1 PMID:7508349

  11. The architectural relationship of components controlling mast cell endocytosis

    PubMed Central

    Cleyrat, Cédric; Darehshouri, Anza; Anderson, Karen L.; Page, Christopher; Lidke, Diane S.; Volkmann, Niels; Hanein, Dorit; Wilson, Bridget S.

    2013-01-01

    Summary Eukaryotic cells use multiple routes for receptor internalization. Here, we examine the topographical relationships of clathrin-dependent and clathrin-independent endocytic structures on the plasma membranes of leukemia-derived mast cells. The high affinity IgE receptor (FcεRI) utilizes both pathways, whereas transferrin receptor serves as a marker for the classical clathrin-mediated endocytosis pathway. Both receptors were tracked by live-cell imaging in the presence or absence of inhibitors that established their differential dependence on specific endocytic adaptor proteins. The topology of antigen-bound FcεRI, clathrin, dynamin, Arf6 and Eps15-positive structures were analyzed by 2D and 3D immunoelectron microscopy techniques, revealing their remarkable spatial relationships and unique geometry. We conclude that the mast cell plasma membrane has multiple specialized domains for endocytosis. Their close proximity might reflect shared components, such as lipids and adaptor proteins, that facilitate inward membrane curvature. Intersections between these specialized domains might represent sorting stations that direct cargo to specific endocytic pathways. PMID:23986485

  12. Propagation by Cutting of Grewia coriacea Mast. (Malvaceae).

    PubMed

    Mercier, Bita Alain; Attibayéba; Pierre, Kampé Jean; Léon, Ngantsoué; Fidèle, Mialoundama

    2016-01-01

    Congolese forests contain important spontaneous food plants. Among these plants, there is the Grewia coriacea Mast., called in the national language "Tsui-téké", which is a tree of 4-25 m high and of 12-40 cm in diameter. Its fruits are used in several drinks making (juice, sparkling wine, syrup) and lollipops. Grewia's barks are used in pharmacopoeia to cure of stomach aches, syphilis. However, the fruits harvesting method based on branches or trees cutting as well as swidden agriculture by local people dangerously threatens the Grewia in the natural ecosystems of Congo. To insure the longevity of this species, we undertook trials of vegetative reproduction of the plant by means of propagation by cuttings for its domestication. Less woody leafless cuttings of 30 cm in length provided best results with a resumption rate of 63.3%, a good rooting production and an average duration of the apparent plastochrone of three days from the second to the fifth leaf. The study shows that domestication of the Grewia coriacea Mast. is possible today by cuttings. Its culture might allow the diversification of species which can be used in orchards. PMID:26930798

  13. Inhibitory Effects of Angelica Polysaccharide on Activation of Mast Cells

    PubMed Central

    Mao, Wei-An; Sun, Yuan-Yuan; Mao, Jing-Yi; Wang, Li; Zhang, Jian; Zhou, Jie; Rahman, Khalid; Ye, Ying

    2016-01-01

    This study was designed to investigate the inhibitory effects of Angelica polysaccharide (AP) on activation of mast cells and its possible molecular mechanism. In our study, we determined the proinflammatory cytokines and allergic mediators in anti-DNP IgE stimulated RBL-2H3 cells and found that AP (50, 100, and 200 μg/mL) significantly decreased the release of histamine, β-hexosaminidase, leukotrienes C4 (LTC4), IL-1, IL-4, TNF-α, IL-6, and human monocyte chemotactic protein-1 (MCP-1/CCL2) (p < 0.05). In addition, Ca2+ entry was inhibited by treatment with AP. AP also downregulated the protein expressions of p-Fyn, p-Akt, p-P38, IL-4, TNF-α, and NF-κB p65 in both Fyn gene upregulated and normal RBL-2H3 cells (p < 0.05). Collectively, our results showed that AP could inhibit the activation of mast cells via suppressing the releases of proinflammatory cytokines allergic mediators, Gab2/PI3-K/Akt and Fyn/Syk pathways. PMID:27200102

  14. Analysis and simulation of the MAST (COFS-1 flight hardware)

    NASA Technical Reports Server (NTRS)

    Horta, Lucas G.; Walsh, Joanne L.; Horner, Garnett C.; Bailey, James P.

    1986-01-01

    In-house analysis work in support of the Control of Flexible Structures (COFS) program is being performed at the NASA Langley Research Center. The work involves evaluation of the proposed design configuration, controller design as well as actuator dynamic modeling, and MAST/actuator dynamic simulation of excitation and damping. A complete finite element model of the MAST has been developed. This finite element model has been incorporated into an optimization procedure which minimizes total mass while maintaining modal coupling. Results show an increase in the total mass due to additional constraints (namely, the diagonal frequency constraint) imposed on the baseline design. A valid actuator dynamic model is presented and a complete test sequence of the proposed flight experiment is demonstrated. The actuator dynamic model is successfully used for damping and the stroke limitations for first mode excitation are demonstrated. Plans are to incorporate additional design variables and constraints into the optimization procedure (such as actuator location) and explore alternative formulations of the objective function. A different actuator dynamic model to include hardware limitations will be investigated.

  15. Electron and ion heating characteristics during magnetic reconnection in MAST

    NASA Astrophysics Data System (ADS)

    Tanabe, Hiroshi; Yamada, Takuma; Watanabe, Takenori; Gi, Keii; Kadowaki, Kazutake; Inomoto, Michiaki; Imazawa, Ryota; Gryaznevich, Mikhail; Michael, Clive; Conway, Neil; Scannell, Rory; Crowley, Brendan; McClements, Ken; Ono, Yasushi; MAST Team

    2015-11-01

    Localized electron heating at X point and global ion heating in the downstream during merging/reconnection startup of ST in MAST have been studied in detail using 130 channel YAG- and 300 channel Ruby-Thomson scattering measurement and a new 32 chord ion Doppler tomography diagnostics. In addition to the previously achieved record heating of ~1keV, 2D profile of electron temperature revealed highly localized heating structure at X point with the characteristic scale length of 0.02-0.05m < c /ωpi , while the ion temperature increases in the downstream of outflow jet with the width of c /ωpi ~ 0 . 1 m where reconnected field forms thick layer of closed flux surface. The effect of Ti -Te energy relaxation also affects both heating profiles in MAST, finally the formation of triple peak structure for both profiles was observed with the delay of τeiE. The toroidal guide field mostly contributes to the formation of a localized electron heating structure at the X point but not to bulk ion heating downstream. This work is supported by JSPS KAKENHI Grant Number 15H05750 and 15K20921.

  16. Electrogene therapy with interleukin-12 in canine mast cell tumors

    PubMed Central

    Pavlin, Darja; Cemazar, Maja; Cör, Andrej; Sersa, Gregor; Pogacnik, Azra; Tozon, Natasa

    2011-01-01

    Background Mast cell tumors (MCT) are the most common malignant cutaneous tumors in dogs with extremely variable biological behaviour. Different treatment approaches can be used in canine cutaneous MCT, with surgical excision being the treatment of choice. In this study, electrogene therapy (EGT) as a new therapeutic approach to canine MCTs, was established. Materials and methods. Eight dogs with a total of eleven cutaneous MCTs were treated with intratumoral EGT using DNA plasmid encoding human interleukin-12 (IL-12). The local response to the therapy was evaluated by repeated measurements of tumor size and histological examination of treated tumors. A possible systemic response was assessed by determination of IL-12 and interferon- γ (IFN-γ) in patients’ sera. The occurence of side effects was monitored with weekly clinical examinations of treated animals and by performing basic bloodwork, consisting of the complete bloodcount and determination of selected biochemistry parameters. Results Intratumoral EGT with IL-12 elicits significant reduction of treated tumors’ size, ranging from 13% to 83% (median 50%) of the initial tumor volume. Additionally, a change in the histological structure of treated nodules was seen. There was a reduction in number of malignant mast cells and inflammatory cell infiltration of treated tumors. Systemic release of IL-12 in four patients was detected, without any noticeable local or systemic side effects. Conclusions These data suggest that intratumoral EGT with plasmid encoding IL-12 may be useful in the treatment of canine MCTs, exerting a local antitumor effect. PMID:22933932

  17. Microstability analysis of pellet fuelled discharges in MAST

    NASA Astrophysics Data System (ADS)

    Garzotti, L.; Figueiredo, J.; Roach, C. M.; Valovič, M.; Dickinson, D.; Naylor, G.; Romanelli, M.; Scannell, R.; Szepesi, G.; the MAST Team

    2014-03-01

    Reactor grade plasmas are likely to be fuelled by pellet injection. This technique transiently perturbs the profiles, driving the density profile hollow and flattening the edge temperature profile. After the pellet perturbation, the density and temperature profiles relax towards their quasi-steady-state shape. Microinstabilities influence plasma confinement and will play a role in determining the evolution of the profiles in pellet fuelled plasmas. In this paper we present the microstability analysis of pellet fuelled H-mode MAST plasmas. Taking advantage of the unique capabilities of the MAST Thomson scattering system and the possibility of synchronizing the eight lasers with the pellet injection, we were able to measure the evolution of the post-pellet electron density and temperature profiles with high temporal and spatial resolution. These profiles, together with ion temperature profiles measured using a charge exchange diagnostic, were used to produce equilibria suitable for microstability analysis of the equilibrium changes induced by pellet injection. This analysis, carried out using the local gyrokinetic code GS2, reveals that the microstability properties are extremely sensitive to the rapid and large transient excursions of the density and temperature profiles, which also change collisionality and βe significantly in the region most strongly affected by the pellet ablation.

  18. Modulations of histamine release from mast cells by interleukin-2 is affected by nedocromil sodium.

    PubMed

    Rubinchik, E; Norris, A; Levi-Schaffer, F

    1995-07-01

    We have previously demonstrated that histamine release from immunologically activated mast cells (MC) is enhanced by their preincubation (1 h) with interleukin-2(IL-2), and that IL-2 induces slow-chronic histamine release by MC in long-term cultures (6 days). In the present study we assessed whether nedocromil sodium can interfere with IL-2 modulation of MC histamine release. IL-2 enhancing effects nedocromil sodium activity were studied in cocultures of rat peritoneal MC with 3T3 fibroblasts (MC/3T3). MC/3T3 were preincubated for 1 h with IL-2 (50 micrograms/ml) and activated with either rabbit anti-rat IgE or compound 48/80. In chronic experiments MC/3T3 were long-term (5-6 days) incubated with IL-2 (50 micrograms/ml). Nedocromil sodium was used at 10(-5) M. MC activation both when added during the preincubation period (no tachyphylaxis was present) and when added together with the MC activators (30-50% inhibition). Washing out IL-2 before addition of the anti-IgE antibodies did not affect its histamine-release enhancing activity. Removal of nedocromil sodium before addition of the stimulus completely abrogated its effect. Continuous presence of IL-2 in the culture medium enhanced spontaneous histamine release by 37% and this effect was completely abolished in the presence of nedocromil sodium. Furthermore, nedocromil sodium decreased MC basal histamine release by 23% in long-term cocultures. Since IL-2 is known to be elevated in some pathological conditions, our results show that nedocromil sodium inhibits MC activation in an in vitro system which may represent a close resemblance to the in vivo allergic response.

  19. The functional response of a hoarding seed predator to mast seeding.

    PubMed

    Fletcher, Quinn E; Boutin, Stan; Lane, Jeffrey E; LaMontagne, Jalene M; McAdam, Andrew G; Krebs, Charles J; Humphries, Murray M

    2010-09-01

    Mast seeding involves the episodic and synchronous production of large seed crops by perennial plants. The predator satiation hypothesis proposes that mast seeding maximizes seed escape because seed predators consume a decreasing proportion of available seeds with increasing seed production. However, the seed escape benefits of masting depend not only on whether predators are satiated at high levels of seed production, but also on the shape of their functional response (type II vs. type III), and the actual proportion of available seeds that they consume at different levels of seed production. North American red squirrels (Tamiasciurus hudsonicus) are the primary vertebrate predator of white spruce (Picea glauca) mast seed crops in many boreal regions because they hoard unopened cones in underground locations, preempting the normal sequence of cone opening, seed dispersal, and seed germination. We document the functional response of cone-hoarding by red squirrels across three non-mast years and one mast year by estimating the number of cones present in the territories of individual red squirrels and the proportion of these cones that they hoarded each autumn. Even though red squirrels are not constrained by the ingestive and on-body (fat reserves) energy reserve limitations experienced by animals that consume seeds directly, most squirrels hoarded < 10% of the cones present on their territories under mast conditions. Cone availability during non-mast years also reached levels that satiated the hoarding activity of red squirrels; however, this occurred only on the highest-quality territories. Squirrels switched to mushroom-hoarding when cone production was low and mushrooms were abundant. This resulted in type III functional response whereby the proportional harvest of cones was highest at levels of cone availability that were intermediate within non-mast years. Overall, more cones escaped squirrel cone-hoarding during a mast event than when cone production was low

  20. Dendritic cell-based vaccines in the setting of peripheral blood stem cell transplantation: CD34+ cell-depleted mobilized peripheral blood can serve as a source of potent dendritic cells.

    PubMed

    Choi, D; Perrin, M; Hoffmann, S; Chang, A E; Ratanatharathorn, V; Uberti, J; McDonagh, K T; Mulé, J J

    1998-11-01

    We are investigating the use of tumor-pulsed dendritic cell (DC)-based vaccines in the treatment of patients with advanced cancer. In the current study, we evaluated the feasibility of obtaining both CD34+ hematopoietic stem/ progenitor cells (HSCs) and functional DCs from the same leukapheresis collection in adequate numbers for both peripheral blood stem cell transplantation (PBSCT) and immunization purposes, respectively. Leukapheresis collections of mobilized peripheral blood mononuclear cells (PBMCs) were obtained from normal donors receiving granulocyte colony-stimulating factor (G-CSF) (for allogeneic PBSCT) and from intermediate grade non-Hodgkin's lymphoma or multiple myeloma patients receiving cyclophosphamide plus G-CSF (for autologous PBSCT). High enrichment of CD34+ HSCs was obtained using an immunomagnetic bead cell separation device. After separation, the negative fraction of mobilized PBMCs from normal donors and cancer patients contained undetectable levels of CD34+ HSCs by flow cytometry. This fraction of cells was then subjected to plastic adherence, and the adherent cells were cultured for 7 days in GM-CSF (100 ng/ml) and interleukin 4 (50 ng/ml) followed by an additional 7 days in GM-CSF, interleukin 4, and tumor necrosis factor alpha (10 ng/ml) to generate DCs. Harvested DCs represented yields of 4.1+/-1.4 and 5.8+/-5.4% of the initial cells plated from the CD34+ cell-depleted mobilized PBMCs of normal donors and cancer patients, respectively, and displayed a high level expression of CD80, CD86, HLA-DR, and CD11c but not CD14. This phenotypic profile was similar to that of DCs derived from non-CD34+ cell-depleted mobilized PBMCs. DCs generated from CD34+ cell-depleted mobilized PBMCs elicited potent antitetanus as well as primary allogeneic T-cell proliferative responses in vitro, which were equivalent to DCs derived from non-CD34+ cell-depleted mobilized PBMCs. Collectively, these results demonstrate the feasibility of obtaining both DCs and

  1. Regulation of early and delayed radiation responses in rat small intestine by capsaicin-sensitive nerves

    SciTech Connect

    Wang Junru; Zheng Huaien; Kulkarni, Ashwini; Ou Xuemei; Hauer-Jensen, Martin . E-mail: mhjensen@life.uams.edu

    2006-04-01

    Purpose: Mast cells protect against the early manifestations of intestinal radiation toxicity, but promote chronic intestinal wall fibrosis. Intestinal sensory nerves are closely associated with mast cells, both anatomically and functionally, and serve an important role in the regulation of mucosal homeostasis. This study examined the effect of sensory nerve ablation on the intestinal radiation response in an established rat model. Methods and Materials: Rats underwent sensory nerve ablation with capsaicin or sham ablation. Two weeks later, a localized segment of ileum was X-irradiated or sham irradiated. Structural, cellular, and molecular changes were examined 2 weeks (early injury) and 26 weeks (chronic injury) after irradiation. The mast cell dependence of the effect of sensory nerve ablation on intestinal radiation injury was assessed using c-kit mutant (Ws/Ws) mast cell-deficient rats. Results: Capsaicin treatment caused a baseline reduction in mucosal mast cell density, crypt cell proliferation, and expression of substance P and calcitonin gene-related peptide, two neuropeptides released by sensory neurons. Sensory nerve ablation strikingly exacerbated early intestinal radiation toxicity (loss of mucosal surface area, inflammation, intestinal wall thickening), but attenuated the development of chronic intestinal radiation fibrosis (collagen I accumulation and transforming growth factor {beta} immunoreactivity). In mast cell-deficient rats, capsaicin treatment exacerbated postradiation epithelial injury (loss of mucosal surface area), but none of the other aspects of radiation injury were affected by capsaicin treatment. Conclusions: Ablation of capsaicin-sensitive enteric neurons exacerbates early intestinal radiation toxicity, but attenuates development of chronic fibroproliferative changes. The effect of capsaicin treatment on the intestinal radiation response is partly mast cell dependent.

  2. Mast Cells are Important Modifiers of Autoimmune Disease: With so Much Evidence, Why is There Still Controversy?

    PubMed Central

    Brown, Melissa A.; Hatfield, Julianne K.

    2012-01-01

    There is abundant evidence that mast cells are active participants in events that mediate tissue damage in autoimmune disease. Disease-associated increases in mast cell numbers accompanied by mast cell degranulation and elaboration of numerous mast cell mediators at sites of inflammation are commonly observed in many human autoimmune diseases including multiple sclerosis, rheumatoid arthritis, and bullous pemphigoid. In animal models, treatment with mast cell stabilizing drugs or mast cell ablation can result in diminished disease. A variety of receptors including those engaged by antibody, complement, pathogens, and intrinsic danger signals are implicated in mast cell activation in disease. Similar to their role as first responders in infection settings, mast cells likely orchestrate early recruitment of immune cells, including neutrophils, to the sites of autoimmune destruction. This co-localization promotes cellular crosstalk and activation and results in the amplification of the local inflammatory response thereby promoting and sustaining tissue damage. Despite the evidence, there is still a debate regarding the relative role of mast cells in these processes. However, by definition, mast cells can only act as accessory cells to the self-reactive T and/or antibody driven autoimmune responses. Thus, when evaluating mast cell involvement using existing and somewhat imperfect animal models of disease, their importance is sometimes obscured. However, these potent immune cells are undoubtedly major contributors to autoimmunity and should be considered as important targets for therapeutic disease intervention. PMID:22701454

  3. Mast Cell-Derived Tumor Necrosis Factor Can Promote Nerve Fiber Elongation in the Skin during Contact Hypersensitivity in Mice

    PubMed Central

    Kakurai, Maki; Monteforte, Rossella; Suto, Hajime; Tsai, Mindy; Nakae, Susumu; Galli, Stephen J.

    2006-01-01

    In humans, lesions of contact eczema or atopic dermatitis can exhibit increases in epidermal nerves, but the mechanism resulting in such nerve elongation are not fully understood. We found that contact hypersensitivity reactions to oxazolone in mice were associated with significant increases in the length of nerves in the epidermis and dermis. Using genetically mast cell-deficient c-kit mutant mice selectively repaired of their dermal mast cell deficiency with either wild-type or tumor necrosis factor (TNF)-deficient mast cells, we found that mast cells, and mast cell-derived TNF, significantly contributed to the elongation of epidermal and dermal PGP 9.5+ nerves and dermal CGRP+ nerves, as well as to the inflammation observed at sites of contact hypersensitivity in response to oxazolone. Moreover, the percentage of mast cells in close proximity to dermal PGP 9.5+ nerve fibers was significantly higher in wild-type mice and in c-kit mutant mice repaired of their dermal mast cell deficiency by the adoptive transfer of wild-type mast cells than in TNF-deficient mice or in TNF−/− mast cell-engrafted c-kit mutant mice. These observations show that mast cells, and mast cell-derived TNF, can promote the elongation of cutaneous nerve fibers during contact hypersensitivity in the mouse. PMID:17071594

  4. A TRPV2–PKA Signaling Module for Transduction of Physical Stimuli in Mast Cells

    PubMed Central

    Stokes, Alexander J.; Shimoda, Lori M.N.; Koblan-Huberson, Murielle; Adra, Chaker N.; Turner, Helen

    2004-01-01

    Cutaneous mast cell responses to physical (thermal, mechanical, or osmotic) stimuli underlie the pathology of physical urticarias. In vitro experiments suggest that mast cells respond directly to these stimuli, implying that a signaling mechanism couples functional responses to physical inputs in mast cells. We asked whether transient receptor potential (vanilloid) (TRPV) cation channels were present and functionally coupled to signaling pathways in mast cells, since expression of this channel subfamily confers sensitivity to thermal, osmotic, and pressure inputs. Transcripts for a range of TRPVs were detected in mast cells, and we report the expression, surface localization, and oligomerization of TRPV2 protein subunits in these cells. We describe the functional coupling of TRPV2 protein to calcium fluxes and proinflammatory degranulation events in mast cells. In addition, we describe a novel protein kinase A (PKA)–dependent signaling module, containing PKA and a putative A kinase adapter protein, Acyl CoA binding domain protein (ACBD)3, that interacts with TRPV2 in mast cells. We propose that regulated phosphorylation by PKA may be a common pathway for TRPV modulation. PMID:15249591

  5. Methoxychlor enhances degranulation of murine mast cells by regulating FcεRI-mediated signal transduction.

    PubMed

    Yasunaga, Sho; Nishi, Kosuke; Nishimoto, Sogo; Sugahara, Takuya

    2015-01-01

    Methoxychlor, an organochlorine insecticide developed to replace DDT (dichlorodiphenyltrichloroethane), has been reported to induce mast cell degranulation and to enhance IgE-mediated allergic responses. However, the mechanisms underlying these effects are not clear. To clarify potential mechanisms, the effects of methoxychlor on degranulation of mast cells were examined. Degranulation responses were evaluated using RBL-2H3 cells and mouse bone marrow-derived mast cells with either the antigen-induced or calcium ionophore-induced stimulation. Phosphorylation of enzymes related to signaling events associated with mast cell degranulation was analyzed by immunoblotting. Effects on vascular permeability in the passive cutaneous anaphylaxis reaction were evaluated following oral administration of methoxychlor to BALB/c mice. The results indicated that methoxychlor caused increased mast cell degranulation in the presence of antigen, whereas it had no effect on calcium ionophore-induced degranulation of RBL-2H3 cells. Immunoblot analyses demonstrated that the phosphorylation level of phosphoinositide 3-kinase (which plays a central role in mast cell signaling) was increased by methoxychlor during antigen-induced degranulation. In addition, methoxychlor activated the signaling pathway via the high-affinity IgE receptor by inducing phosphorylation of Syk and PLCγ1/2, which transfer the signal for degranulation downstream. Lastly, oral administration of methoxychlor exhibited a tendency to promote vascular permeability in passive cutaneous anaphylaxis model mice. Taken together, the results here suggested that methoxychlor enhanced degranulation through FcεRI-mediated signaling and promoted allergenic symptoms involved in mast cell degranulation.

  6. Tetraspanin CD151 Is a Negative Regulator of FcεRI-Mediated Mast Cell Activation

    PubMed Central

    Abdala-Valencia, Hiam; Bryce, Paul J.; Schleimer, Robert P.; Wechsler, Joshua B.; Loffredo, Lucas F.; Cook-Mills, Joan M.; Hsu, Chia-Lin; Berdnikovs, Sergejs

    2016-01-01

    Mast cells are critical in the pathogenesis of allergic disease due to the release of preformed and newly synthesized mediators, yet the mechanisms controlling mast cell activation are not well understood. Members of the tetraspanin family are recently emerging as modulators of FcεRI-mediated mast cell activation; however, mechanistic understanding of their function is currently lacking. The tetraspanin CD151 is a poorly understood member of this family and is specifically induced on mouse and human mast cells upon FcεRI aggregation but its functional effects are unknown. In this study, we show that CD151 deficiency significantly exacerbates the IgE-mediated late phase inflammation in a murine model of passive cutaneous anaphylaxis. Ex vivo, FcεRI stimulation of bone marrow–derived mast cells from CD151−/− mice resulted in significantly enhanced expression of proinflammatory cytokines IL-4, IL-13, and TNF-α compared with wild-type controls. However, FcεRI -induced mast cell degranulation was unaffected. At the molecular signaling level, CD151 selectively regulated IgE-induced activation of ERK1/2 and PI3K, associated with cytokine production, but had no effect on the phospholipase Cγ1 signaling, associated with degranulation. Collectively, our data indicate that CD151 exerts negative regulation over IgE-induced late phase responses and cytokine production in mast cells. PMID:26136426

  7. Mast cell activation by conidia of Sporothrix schenckii: role in the severity of infection.

    PubMed

    Romo-Lozano, Y; Hernández-Hernández, F; Salinas, E

    2012-07-01

    Mast cells are abundant in the skin and other peripheral tissues, where they are one of the first immune cells to make contact with invading pathogens. As a result of pathogen recognition, mast cells can be activated and release different preformed and de novo-synthesized mediators. Sporothrix schenckii is the fungus that causes sporotrichosis, a worldwide-distributed subcutaneous mycosis considered as an important emerging health problem. It remains unknown whether or not mast cells are activated by S. schenckii. Here, we investigated the in vitro response of mast cells to conidia of S. schenckii and their in vivo involvement in sporotrichosis. Mast cells became activated after interaction with conidia, releasing early response cytokines as TNF-α and IL-6. Although histamine release was not significantly stimulated by S. schenckii, we determined that conidia potentiate histamine secretion induced by compound 48/80. Furthermore, functional depletion of peritoneal mast cells before S. schenckii infection significantly reduced the severity of cutaneous lesions of the sporotrichosis. These data demonstrate that mast cells are important contributors in the host response to S. schenckii infection, suggesting a role of these cells in the progress of clinical manifestations in sporotrichosis. PMID:22486186

  8. Mast cell activation by conidia of Sporothrix schenckii: role in the severity of infection.

    PubMed

    Romo-Lozano, Y; Hernández-Hernández, F; Salinas, E

    2012-07-01

    Mast cells are abundant in the skin and other peripheral tissues, where they are one of the first immune cells to make contact with invading pathogens. As a result of pathogen recognition, mast cells can be activated and release different preformed and de novo-synthesized mediators. Sporothrix schenckii is the fungus that causes sporotrichosis, a worldwide-distributed subcutaneous mycosis considered as an important emerging health problem. It remains unknown whether or not mast cells are activated by S. schenckii. Here, we investigated the in vitro response of mast cells to conidia of S. schenckii and their in vivo involvement in sporotrichosis. Mast cells became activated after interaction with conidia, releasing early response cytokines as TNF-α and IL-6. Although histamine release was not significantly stimulated by S. schenckii, we determined that conidia potentiate histamine secretion induced by compound 48/80. Furthermore, functional depletion of peritoneal mast cells before S. schenckii infection significantly reduced the severity of cutaneous lesions of the sporotrichosis. These data demonstrate that mast cells are important contributors in the host response to S. schenckii infection, suggesting a role of these cells in the progress of clinical manifestations in sporotrichosis.

  9. Meningeal mast cell-T cell crosstalk regulates T cell encephalitogenicity.

    PubMed

    Russi, Abigail E; Walker-Caulfield, Margaret E; Guo, Yong; Lucchinetti, Claudia F; Brown, Melissa A

    2016-09-01

    GM-CSF is a cytokine produced by T helper (Th) cells that plays an essential role in orchestrating neuroinflammation in experimental autoimmune encephalomyelitis, a rodent model of multiple sclerosis. Yet where and how Th cells acquire GM-CSF expression is unknown. In this study we identify mast cells in the meninges, tripartite tissues surrounding the brain and spinal cord, as important contributors to antigen-specific Th cell accumulation and GM-CSF expression. In the absence of mast cells, Th cells do not accumulate in the meninges nor produce GM-CSF. Mast cell-T cell co-culture experiments and selective mast cell reconstitution of the meninges of mast cell-deficient mice reveal that resident meningeal mast cells are an early source of caspase-1-dependent IL-1β that licenses Th cells to produce GM-CSF and become encephalitogenic. We also provide evidence of mast cell-T cell co-localization in the meninges and CNS of recently diagnosed acute MS patients indicating similar interactions may occur in human demyelinating disease. PMID:27396526

  10. Zinc Oxide Nanoparticles Demoted MDM2 Expression to Suppress TSLP-Induced Mast Cell Proliferation.

    PubMed

    Kim, Min-Ho; Jeong, Hyun-Ja

    2016-03-01

    Activation of murine double minute 2 (MDM2) through thymic stromal lymphopoietin (TSLP)-induced signal transducers and activators of transcription (STAT6) phosphorylation plays a critical role in proliferation and survival of mast cells. Previously, we reported that zinc oxide nanoparticles (ZnO-NP) effectively decrease the mast cell-mediated allergic inflammatory reactions. Here, we evaluated the effect of ZnO-NP on TSLP-induced proliferation of mast cells. ZnO-NP significantly reduced the number of BrdU-incorporating mast cells increased by TSLP. ZnO-NP decreased the expression of MDM2 through the blockade of STAT6 phosphorylation. TSLP increased the production and mRNA expression of interleukin-13 (a growth factor of mast cells), its increase was significantly decreased by ZnO-NP (10 μg/mL). ZnO-NP induced the down-regulation of Bcl2 (an anti-apoptotic factor) and up-regulation of Bax (an apoptotic factor) through the stabilization of p53 protein. However, ZnO-NP has no effect on caspase-3 activation, cytochrome c release into cytosol, and apoptosis-inducing factor translocation into nucleus in TSLP-stimulated cells. The results of the present study demonstrated that ZnO-NP inhibited the proliferation of mast cells through the regulation of MDM2 and p53 protein levels. These finding suggest that ZnO-NP could be improved mast cell-mediated various diseases.

  11. Our perception of the mast cell from Paul Ehrlich to now.

    PubMed

    Beaven, Michael A

    2009-01-01

    Just over a century ago Paul Ehrlich received the Nobel Prize for his studies of immunity. This review describes one of his legacies, the histochemical description of the mast cell, and the research that has ensued since then. After a long period of largely descriptive studies, which revealed little about the biological role of the mast cell, the field was galvanized in the 1950s by the recognition that the mast cell was the main repository of histamine and a key participant in anaphylactic reactions. Although the mast cell was long-viewed in these terms, recent research has now shown that the mast cell also plays a key role in innate and adaptive immune responses, autoimmune disease, and possibly tissue homeostasis by virtue of its expression of a diverse array of receptors and biologically active products. In addition, the responsiveness of mast cells to immunological and pathological stimulants is highly modulated by the tissue cytokine environment and by synergistic, or inhibitory, interactions among the various mast cell receptor systems. This once enigmatic cell of Paul Ehrlich has proved to be both adaptable and multifunctional.

  12. Mast cells are dispensable in a genetic mouse model of chronic dermatitis.

    PubMed

    Sulcova, Jitka; Meyer, Michael; Guiducci, Eva; Feyerabend, Thorsten B; Rodewald, Hans-Reimer; Werner, Sabine

    2015-06-01

    Chronic inflammatory skin diseases, such as atopic dermatitis, affect a large percentage of the population, but the role of different immune cells in the pathogenesis of these disorders is largely unknown. Recently, we found that mice lacking fibroblast growth factor receptor 1 (Fgfr1) and Fgfr2 (K5-R1/R2 mice) in the epidermis have a severe impairment in the epidermal barrier, which leads to the development of a chronic inflammatory skin disease that shares many features with human atopic dermatitis. Using Fgfr1-/Fgfr2-deficient mice, we analyzed the consequences of the loss of mast cells. Mast cells accumulated and degranulated in the skin of young Fgfr1-/Fgfr2-deficient mice, most likely as a consequence of increased expression of the mast cell chemokine Ccl2. The increase in mast cells occurred before the development of histological abnormalities, indicating a functional role of these cells in the inflammatory skin phenotype. To test this hypothesis, we mated the Fgfr1-/Fgfr2-deficient mice with mast cell-deficient CreMaster mice. Surprisingly, loss of mast cells did not or only mildly affect keratinocyte proliferation, epidermal thickness, epidermal barrier function, accumulation and activation of different immune cells, or expression of different proinflammatory cytokines in the skin. These results reveal that mast cells are dispensable for the development of chronic inflammation in response to a defect in the epidermal barrier.

  13. Myocardial remodeling in diabetic cardiomyopathy associated with cardiac mast cell activation.

    PubMed

    Huang, Zhi Gang; Jin, Qun; Fan, Min; Cong, Xiao Liang; Han, Shu Fang; Gao, Hai; Shan, Yi

    2013-01-01

    Diabetic cardiomyopathy is a specific disease process distinct from coronary artery disease and hypertension. The disease features cardiac remodeling stimulated by hyperglycemia of the left ventricle wall and disrupts contractile functions. Cardiac mast cells may be activated by metabolic byproducts resulted from hyperglycermia and then participate in the remodeling process by releasing a multitude of cytokines and bioactive enzymes. Nedocromil, a pharmacologic stabilizer of mast cells, has been shown to normalize cytokine levels and attenuate cardiac remodeling. In this study, we describe the activation of cardiac mast cells by inducing diabetes in normal mice using streptozotocin (STZ). Next, we treated the diabetic mice with nedocromil for 12 weeks and then examined their hearts for signs of cardiac remodeling and quantified contractile function. We observed significantly impaired heart function in diabetic mice, as well as increased cardiac mast cell density and elevated mast cell secretions that correlated with gene expression and aberrant cytokine levels associated with cardiac remodeling. Nedocromil treatment halted contractile dysfunction in diabetic mice and reduced cardiac mast cell density, which correlated with reduced bioactive enzyme secretions, reduced expression of extracellular matrix remodeling factors and collagen synthesis, and normalized cytokine levels. However, the results showed nedocromil treatments did not return diabetic mice to a normal state. We concluded that manipulation of cardiac mast cell function is sufficient to attenuate cardiomyopathy stimulated by diabetes, but other cellular pathways also contribute to the disease process.

  14. The lectin ArtinM binds to mast cells inducing cell activation and mediator release.

    PubMed

    Barbosa-Lorenzi, Valéria Cintra; Buranello, Patrícia Andressa de Almeida; Roque-Barreira, Maria Cristina; Jamur, Maria Célia; Oliver, Constance; Pereira-da-Silva, Gabriela

    2011-12-16

    Mast cells are inflammatory cells that respond to signals of innate and adaptive immunity with immediate and delayed release of mediators. ArtinM, a lectin from Artocarpus integrifolia with immunomodulatory activities, is able to induce mast cell activation, but the mechanisms remain unknown. This study sought to further investigate the effects of the lectin on mast cells. We showed that ArtinM binds to mast cells, possibly to the high affinity receptor for immunoglobulin E (IgE) - FcεRI - and/or to IgE bound to FcεRI. Binding of the lectin resulted in protein tyrosine phosphorylation and release of the pre- and newly-formed mediators, β-hexosaminidase and LTB(4) by mast cells, activities that were potentiated in the presence of IgE. ArtinM also induced the activation of the transcription factors NFκB and NFAT, resulting in expression of some of their target genes such as IL-4 and TNF-α. In view of the established significance of mast cells in many immunological and inflammatory reactions, a better understanding of the mechanisms involved in mast cell activation by ArtinM is crucial to the pharmacological application of the lectin.

  15. Bone marrow-derived cultured mast cells and peritoneal mast cells as targets of a growth activity secreted by BALB/3T3 fibroblasts

    SciTech Connect

    Jozaki, K.; Kuriu, A.; Hirota, S.; Onoue, H.; Ebi, Y.; Adachi, S.; Ma, J.Y.; Tarui, S.; Kitamura, Y. )

    1991-03-01

    When fibroblast cell lines were cultured in contact with bone marrow-derived cultured mast cells (CMC), both NIH/3T3 and BALB/3T3 cell lines supported the proliferation of CMC. In contrast, when contact between fibroblasts and CMC was prohibited by Biopore membranes or soft agar, only BALB/3T3 fibroblasts supported CMC proliferation, suggesting that BALB/3T3 but not NIH/3T3 cells secreted a significant amount of a mast cell growth activity. Moreover, the BALB/3T3-derived growth activity induced the incorporation of (3H)thymidine by CMC and the clonal growth of peritoneal mast cells in methylcellulose. The mast cell growth activity appeared to be different from interleukin 3 (IL-3) and interleukin 4 (IL-4), because mRNAs for these interleukins were not detectable in BALB/3T3 fibroblasts. Although mast cells are genetically deficient in tissues of W/Wv mice, CMC did develop when bone marrow cells of W/Wv mice were cultured with pokeweed mitogen-stimulated spleen cell-conditioned medium. Because BALB/3T3 fibroblast-conditioned medium (BALB-FCM) did not induce the incorporation of (3H)thymidine by W/Wv CMC, the growth activity in BALB-FCM appeared to be a ligand for the receptor encoded by the W (c-kit) locus. Because CMC and peritoneal mast cells are obtained as homogeneous suspensions rather easily, these cells may be potentially useful as targets for the fibroblast-derived mast cell growth activity.

  16. Mast pulses shape trophic interactions between fluctuating rodent populations in a primeval forest.

    PubMed

    Selva, Nuria; Hobson, Keith A; Cortés-Avizanda, Ainara; Zalewski, Andrzej; Donázar, José Antonio

    2012-01-01

    How different functional responses of consumers exploiting pulsed resources affect community dynamics is an ongoing question in ecology. Tree masting is a common resource pulse in terrestrial ecosystems that can drive rodent population cycles. Using stable isotope (δ(13)C, δ(15)N) analyses, we investigated the dietary response of two fluctuating rodent species, the yellow-necked mouse Apodemus flavicollis and the bank vole Myodes glareolus, to mast events in Białowieża Forest (NE Poland). Rodent hair samples were obtained non-invasively from faeces of their predators for an 11-year period that encompassed two mast events. Spectacular seed crops of deciduous trees, namely oak Quercus robur and hornbeam Carpinus betulus, occur after several intermediate years of moderate seed production, with a post-mast year characterised by a nil crop. While a Bayesian isotopic (SIAR) mixing model showed a variety of potential vegetation inputs to rodent diets, the isotopic niche of the yellow-necked mouse was strongly associated with mast of deciduous trees (>80% of diet), showing no variation among years of different seed crop. However, bank voles showed a strong functional response; in mast years the vole shifted its diet from herbs in deciduous forest (~66% of diet) to mast (~74%). Only in mast years did the isotopic niche of both rodent species overlap. Previous research showed that bank voles, subordinate and more generalist than mice, showed higher fluctuations in numbers in response to masting. This study provides unique data on the functional response of key pulse consumers in forest food webs, and contributes to our understanding of rodent population fluctuations and the mechanisms governing pulse-consumer interactions. PMID:23251475

  17. Spatio-temporal availability of soft mast in clearcuts in the Southern Appalachians

    USGS Publications Warehouse

    Reynolds-Hogland, M. J.; Mitchell, M.S.; Powell, R.A.

    2006-01-01

    Soft mast is an important resource for many wild populations in the Southern Appalachians, yet the way clear-cutting affects availability of soft mast though time is not fully understood. We tested a theoretical model of temporal availability of soft mast in clearcuts using empirical data on percent cover and berry production of Gaylussacia, Vaccinium, and Rubus spp. plants in 100 stands that were clearcut (0-122 years old) in the Southern Appalachian Mountains. We modeled the relationship between soft mast availability and stand age, evaluated the effects of topography and forest type on soft mast, developed statistical models for predicting the spatio-temporal distribution of soft mast, and tested the hypothesis that percent cover of berry plants and berry production provided similar information about soft mast availability. We found temporal dynamics explained berry production better than it predicted percent plant cover, whereas topographic variables influenced percent plant cover more than they influenced berry production. Berry production and percent plant cover were highest in ???2-9-year-old stands. Percent plant cover was lowest in 10-69-year-old stands and intermediate in 70+-year-old stands. Three of our spatio-temporal models performed well during model testing and they were not biased by the training data, indicating the inferences about spatio-temporal availability of soft mast extended beyond our sample data. The methods we used to estimate the distribution of soft mast may be useful for modeling distributions of other resources. ?? 2006 Elsevier B.V. All rights reserved.

  18. Design, Fabrication and Testing of Mooring Masts for Remotely Controlled Indoor and Outdoor Airships

    NASA Astrophysics Data System (ADS)

    Khaleelullah, Syed; Bhardwaj, Utsav; Pant, Rajkumar Sureshchandra

    2016-04-01

    This paper presents the design and structural details of two mooring masts, one for remotely controlled outdoor airships and another one for remotely controlled indoor airships. In a previous study, a mast for outdoor remotely controlled airship was designed to meet several user-specified operating requirements, and a simplified version of the same was fabricated. A spring loaded device was incorporated that sounds an alarm when the wind-loads exceed a threshold value, so that the airship can be taken indoors. The present study started with a critical analysis of that mast, and a new mast was designed and fabricated to remove several of its shortcomings. This mast consists of power screw operated telescopic module made of aluminium, mounted on a five legged base with castor wheels, for ease in mobility. Components of the existing mast were used to the possible extent, and the design was simplified to meet the assembly and transportation requirements. The spring mechanism used in alarming device was also modified to ensure higher sensitivity in the range of maximum expected wind-loads acting on the airship. A lightweight mooring mast for indoor remotely controlled airships was also designed and fabricated, which can accommodate non-rigid indoor airships of length up to 5 m. The mast consists of an elevating bolt operated telescopic module mounted on a tripod adapter base, with lockable castor wheels, and has a specially designed mooring-clamp at the top. The various modules and components of the mast were designed to enable quick assembly and transportation.

  19. Histamine from Brain Resident MAST Cells Promotes Wakefulness and Modulates Behavioral States

    PubMed Central

    Chikahisa, Sachiko; Kodama, Tohru; Soya, Atsushi; Sagawa, Yohei; Ishimaru, Yuji; Séi, Hiroyoshi; Nishino, Seiji

    2013-01-01

    Mast cell activation and degranulation can result in the release of various chemical mediators, such as histamine and cytokines, which significantly affect sleep. Mast cells also exist in the central nervous system (CNS). Since up to 50% of histamine contents in the brain are from brain mast cells, mediators from brain mast cells may significantly influence sleep and other behaviors. In this study, we examined potential involvement of brain mast cells in sleep/wake regulations, focusing especially on the histaminergic system, using mast cell deficient (W/Wv) mice. No significant difference was found in the basal amount of sleep/wake between W/Wv mice and their wild-type littermates (WT), although W/Wv mice showed increased EEG delta power and attenuated rebound response after sleep deprivation. Intracerebroventricular injection of compound 48/80, a histamine releaser from mast cells, significantly increased histamine levels in the ventricular region and enhanced wakefulness in WT mice, while it had no effect in W/Wv mice. Injection of H1 antagonists (triprolidine and mepyramine) significantly increased the amounts of slow-wave sleep in WT mice, but not in W/Wv mice. Most strikingly, the food-seeking behavior observed in WT mice during food deprivation was completely abolished in W/Wv mice. W/Wv mice also exhibited higher anxiety and depression levels compared to WT mice. Our findings suggest that histamine released from brain mast cells is wake-promoting, and emphasizes the physiological and pharmacological importance of brain mast cells in the regulation of sleep and fundamental neurobehavior. PMID:24205232

  20. Histamine from brain resident MAST cells promotes wakefulness and modulates behavioral states.

    PubMed

    Chikahisa, Sachiko; Kodama, Tohru; Soya, Atsushi; Sagawa, Yohei; Ishimaru, Yuji; Séi, Hiroyoshi; Nishino, Seiji

    2013-01-01

    Mast cell activation and degranulation can result in the release of various chemical mediators, such as histamine and cytokines, which significantly affect sleep. Mast cells also exist in the central nervous system (CNS). Since up to 50% of histamine contents in the brain are from brain mast cells, mediators from brain mast cells may significantly influence sleep and other behaviors. In this study, we examined potential involvement of brain mast cells in sleep/wake regulations, focusing especially on the histaminergic system, using mast cell deficient (W/W(v)) mice. No significant difference was found in the basal amount of sleep/wake between W/W(v) mice and their wild-type littermates (WT), although W/W(v) mice showed increased EEG delta power and attenuated rebound response after sleep deprivation. Intracerebroventricular injection of compound 48/80, a histamine releaser from mast cells, significantly increased histamine levels in the ventricular region and enhanced wakefulness in WT mice, while it had no effect in W/W(v) mice. Injection of H1 antagonists (triprolidine and mepyramine) significantly increased the amounts of slow-wave sleep in WT mice, but not in W/W(v) mice. Most strikingly, the food-seeking behavior observed in WT mice during food deprivation was completely abolished in W/W(v) mice. W/W(v) mice also exhibited higher anxiety and depression levels compared to WT mice. Our findings suggest that histamine released from brain mast cells is wake-promoting, and emphasizes the physiological and pharmacological importance of brain mast cells in the regulation of sleep and fundamental neurobehavior.

  1. [Mast cells, their adenosine receptors and reactive oxygen species in chronic inflammatory pathologies of childhood].

    PubMed

    Renke, Joanna; Popadiuk, Stefan; Wozniak, Michał; Szlagatys-Sidorkiewicz, Agnieszka; Hansdorfer-Korzon, Rita

    2006-01-01

    Mast cells were described by Erhlich at the end of XIX-th century. Their role was deeply investigated in asthma and allergy. The massive degranulation of mast cells in allergy can lead to anaphylactic shock. Recently, mast cells have been recognized again as a very interesting topic for investigation, due to their possible role in chronic inflammation. Moreover, through adenosine receptors, mast cells can be activated or inactivated. That is why these cells are regarded as a potential target of new drugs. It has been reported, that mast cells generate intracellular reactive oxygen species (ROS) in response to stimulation with divergent physiologically relevant stimulants. The intensification of ROS production may be measured by the level of carbonyl groups, as a marker of protein peroxidation. However, the role of mast cells in other than asthma diseases with chronic inflammation needs further investigation. It was found out that the information about mast cell distribution in colonic mucosa may serve as help in differentiation between inflammatory bowel disease and collagenous colitis. Moreover, its accumulation in focal active gastritis was confirmed in patients with Crohn's disease. An important role in regulation of inflammatory process seems to be reserved for adenosine receptors present on mastocytes. The activation of mast cells through the adenosine receptor is connected with 11-8 release, which stimulate the migration of leukocytes and oxidation reactions. The detection of mast cells in tissues should not be limited only to the simple histologic examination. It should be completed by the detection of products of degranulation, e.g. tryptase. This is the way to find out their actual function and state of activation. PMID:17203808

  2. Mast pulses shape trophic interactions between fluctuating rodent populations in a primeval forest.

    PubMed

    Selva, Nuria; Hobson, Keith A; Cortés-Avizanda, Ainara; Zalewski, Andrzej; Donázar, José Antonio

    2012-01-01

    How different functional responses of consumers exploiting pulsed resources affect community dynamics is an ongoing question in ecology. Tree masting is a common resource pulse in terrestrial ecosystems that can drive rodent population cycles. Using stable isotope (δ(13)C, δ(15)N) analyses, we investigated the dietary response of two fluctuating rodent species, the yellow-necked mouse Apodemus flavicollis and the bank vole Myodes glareolus, to mast events in Białowieża Forest (NE Poland). Rodent hair samples were obtained non-invasively from faeces of their predators for an 11-year period that encompassed two mast events. Spectacular seed crops of deciduous trees, namely oak Quercus robur and hornbeam Carpinus betulus, occur after several intermediate years of moderate seed production, with a post-mast year characterised by a nil crop. While a Bayesian isotopic (SIAR) mixing model showed a variety of potential vegetation inputs to rodent diets, the isotopic niche of the yellow-necked mouse was strongly associated with mast of deciduous trees (>80% of diet), showing no variation among years of different seed crop. However, bank voles showed a strong functional response; in mast years the vole shifted its diet from herbs in deciduous forest (~66% of diet) to mast (~74%). Only in mast years did the isotopic niche of both rodent species overlap. Previous research showed that bank voles, subordinate and more generalist than mice, showed higher fluctuations in numbers in response to masting. This study provides unique data on the functional response of key pulse consumers in forest food webs, and contributes to our understanding of rodent population fluctuations and the mechanisms governing pulse-consumer interactions.

  3. Mast Pulses Shape Trophic Interactions between Fluctuating Rodent Populations in a Primeval Forest

    PubMed Central

    Selva, Nuria; Hobson, Keith A.; Cortés-Avizanda, Ainara; Zalewski, Andrzej; Donázar, José Antonio

    2012-01-01

    How different functional responses of consumers exploiting pulsed resources affect community dynamics is an ongoing question in ecology. Tree masting is a common resource pulse in terrestrial ecosystems that can drive rodent population cycles. Using stable isotope (δ13C, δ15N) analyses, we investigated the dietary response of two fluctuating rodent species, the yellow-necked mouse Apodemus flavicollis and the bank vole Myodes glareolus, to mast events in Białowieża Forest (NE Poland). Rodent hair samples were obtained non-invasively from faeces of their predators for an 11-year period that encompassed two mast events. Spectacular seed crops of deciduous trees, namely oak Quercus robur and hornbeam Carpinus betulus, occur after several intermediate years of moderate seed production, with a post-mast year characterised by a nil crop. While a Bayesian isotopic (SIAR) mixing model showed a variety of potential vegetation inputs to rodent diets, the isotopic niche of the yellow-necked mouse was strongly associated with mast of deciduous trees (>80% of diet), showing no variation among years of different seed crop. However, bank voles showed a strong functional response; in mast years the vole shifted its diet from herbs in deciduous forest (∼66% of diet) to mast (∼74%). Only in mast years did the isotopic niche of both rodent species overlap. Previous research showed that bank voles, subordinate and more generalist than mice, showed higher fluctuations in numbers in response to masting. This study provides unique data on the functional response of key pulse consumers in forest food webs, and contributes to our understanding of rodent population fluctuations and the mechanisms governing pulse–consumer interactions. PMID:23251475

  4. The Role of Macrophage Migration Inhibitory Factor in Mast Cell-Stimulated Fibroblast Proliferation and Collagen Production

    PubMed Central

    Ningyan, Gu; Xu, Yao; Hongfei, Shi; Jingjing, Chen; Min, Chen

    2015-01-01

    Current clinical and translational studies have shown that mast cell plays a pivotal role in multiple fibrotic diseases including scleroderma. However, the lack of mature human mast cell culture model exhibits a major obstacle for further dissection of cytokines and signaling molecules required for mast cell mediated fibrosis in various diseases. Macrophage Migration Inhibitory Factor is a mast cell released pro-inflammatory cytokine which is deregulated in scleroderma patients and is also involved in non-scleroderma related fibrosis. In the current study, we successfully generated a practical and reliable human mast cell culture system with bone marrow CD34+ hematopietic precursors. The derivative mast cell is normal in terms of both morphology and function as manifested by normal degranulation. More importantly, we were able to show mast cell conditioned medium as well as MIF supplementation augments fibroblast proliferation and collagen synthesis. This positive regulatory effect of mast cell conditioned medium can be dampened by MIF antibody. In addition, MIF-knockdown significantly inhibits pro-fibrotic activities of CD34+ hematopietic precursor derived mast cells. These data strongly suggest that mast cell released MIF is required for mast cell mediated fibrogenic activities. The current manuscript seems to be the first mechanistic report showing the significance of MIF in mast cell mediated fibrosis, which may pave the way for the development of potential MIF-targeted therapy for fibrotic diseases to a further extent. Moreover, we strongly believe mast cell culture and differentiation model as well as corresponding genetic manipulation methodology will be helpful in characterizing novel mast cell based therapeutic targets. PMID:25826375

  5. ANTI-INFLAMMATORY AND MAST CELL PROTECTIVE EFFECT OF FICUS RELIGIOSA

    PubMed Central

    Viswanathan, S.; Thirugnanasambantham, P.; Reddy, M. Kannappa; Narasimhan, S.; Subramaniam, G. Anantha

    1990-01-01

    The aqueous extract of bark of Ficus religiosa was prepared and investigated for its anti-inflammatory effect and for its protective effect on mast cells against degranulation. A significant anti-inflammatory effect was observed in both acute and chronic models of inflammation. The extract also protected mast cells from degranulation induced by various degranulatiors. The observed anti-inflammatory and mast cell protective effect may be responsible for the beneficial effect of Ficus religiosa in kumkum dermatitis and other inflammatory conditions. PMID:22556521

  6. Anti-inflammatory and mast cell protective effect of ficus religiosa.

    PubMed

    Viswanathan, S; Thirugnanasambantham, P; Reddy, M K; Narasimhan, S; Subramaniam, G A

    1990-10-01

    The aqueous extract of bark of Ficus religiosa was prepared and investigated for its anti-inflammatory effect and for its protective effect on mast cells against degranulation. A significant anti-inflammatory effect was observed in both acute and chronic models of inflammation. The extract also protected mast cells from degranulation induced by various degranulatiors. The observed anti-inflammatory and mast cell protective effect may be responsible for the beneficial effect of Ficus religiosa in kumkum dermatitis and other inflammatory conditions. PMID:22556521

  7. New Developments in Mast Cell Biology: Clinical Implications.

    PubMed

    Arthur, Greer; Bradding, Peter

    2016-09-01

    Mast cells (MCs) are present in connective tissue and at mucosal surfaces in all classes of vertebrates. In health, they contribute to tissue homeostasis, host defense, and tissue repair via multiple receptors regulating the release of a vast stockpile of proinflammatory mediators, proteases, and cytokines. However, these potentially protective cells are a double-edged sword. When there is a repeated or long-term stimulus, MC activation leads to tissue damage and dysfunction. Accordingly, MCs are implicated in the pathophysiologic aspects of numerous diseases covering all organs. Understanding the biology of MCs, their heterogeneity, mechanisms of activation, and signaling cascades may lead to the development of novel therapies for many diseases for which current treatments are lacking or are of poor efficacy. This review will focus on updates and developments in MC biology and their clinical implications, with a particular focus on their role in respiratory diseases.

  8. A novel model of IgE-mediated passive pulmonary anaphylaxis in rats.

    PubMed

    Wex, Eva; Thaler, Eva; Blum, Sylvia; Lamb, David

    2014-01-01

    Mast cells are central effector cells in allergic asthma and are augmented in the airways of asthma patients. Attenuating mast cell degranulation and with it the early asthmatic response is an important intervention point to inhibit bronchoconstriction, plasma exudation and tissue oedema formation. To validate the efficacy of novel pharmacological interventions, appropriate and practicable in vivo models reflecting mast cell-dependent mechanisms in the lung, are missing. Thus, we developed a novel model of passive pulmonary anaphylaxis in rats. Rats were passively sensitized by concurrent intratracheal and intradermal (ear) application of an anti-DNP IgE antibody. Intravenous application of the antigen, DNP-BSA in combination with Evans blue dye, led to mast cell degranulation in both tissues. Quantification of mast cell degranulation in the lung was determined by (1) mediator release into bronchoalveolar lavage, (2) extravasation of Evans blue dye into tracheal and bronchial lung tissue and (3) invasive measurement of antigen-induced bronchoconstriction. Quantification of mast cell degranulation in the ear was determined by extravasation of Evans blue dye into ear tissue. We pharmacologically validated our model using the SYK inhibitor Fostamatinib, the H1-receptor antagonist Desloratadine, the mast cell stabilizer disodium cromoglycate (DSCG) and the β2-adrenergic receptor agonist Formoterol. Fostamatinib was equally efficacious in lung and ear. Desloratadine effectively inhibited bronchoconstriction and ear vascular leakage, but was less effective against pulmonary vascular leakage, perhaps reflecting the differing roles for histamine receptor sub-types. DSCG attenuated both vascular leakage in the lung and bronchoconstriction, but with a very short duration of action. As an inhaled approach, Formoterol was more effective in the lung than in the ear. This model of passive pulmonary anaphylaxis provides a tissue relevant readout of early mast cell activity and

  9. The envelope gp120 gene of human immunodeficiency virus type 1 determines the rate of CD4-positive T-cell depletion in SCID mice engrafted with human peripheral blood leukocytes.

    PubMed Central

    Gulizia, R J; Levy, J A; Mosier, D E

    1996-01-01

    We have used envelope recombinant viruses generated between two molecular clones of human immunodeficiency virus type 1 (HIV-1), T-cell-tropic HIV-1SF2 and macrophage-tropic HIV-1SF162, to assess pathogenic potential in the human peripheral blood leukocyte-reconstituted severe combined immune deficiency mouse model. Recombinant HIV-1SF2 viruses expressing the envelope gp120 gene of HIV-ISF162 caused as rapid a CD4+ T-cell depletion as did HIV-1SF162. The reciprocal HIV-1SF162 recombinant virus with the HIV-1SF2 envelope caused slower CD4+ T-cell loss. Although changing the V3 loop sequence of HIV-1SF162 to that of HIV-1SF2 did not change the rate of CD4+ T-cell depletion, replacing the V3 of HIV-1SF2 with the sequence of HIV-1SF162 resulted in virus that was poorly infectious in vivo but not in vitro. These studies suggest that the envelope gene determines properties important for pathogenesis in vivo as well as for cell tropism in vitro. HIV-1 infection in vivo may have more stringent requirements for envelope conformation. PMID:8648765

  10. Effects of T cell depletion in radiation bone marrow chimeras. I. Evidence for a donor cell population which increases allogeneic chimerism but which lacks the potential to produce GVHD

    SciTech Connect

    Sykes, M.; Sheard, M.; Sachs, D.H.

    1988-10-01

    The opposing problems of graft-vs-host disease (GVHD) and failure of alloengraftment present major obstacles to the application of bone marrow transplantation (BMT) across complete MHC barriers. The addition of syngeneic T-cell-depleted (TCD) bone marrow (BM) to untreated fully allogeneic marrow inocula in lethally irradiated mice has been previously shown to provide protection from GVHD. We have used this model to study the effects of allogeneic T cells on levels of chimerism in recipients of mixed marrow inocula. The results indicate that T cells in allogeneic BM inocula eliminate both coadministered recipient-strain and radioresistant host hematopoietic elements to produce complete allogeneic chimerism without clinical GVHD. To determine the role of GVH reactivity in this phenomenon, we performed similar studies in an F1 into parent combination, in which the genetic potential for GVHD is lacking. The presence of T cells in F1 marrow inocula led to predominant repopulation with F1 lymphocytes in such chimeras, even when coadministered with TCD-recipient-strain BM. These results imply that the ability of allogeneic BM cells removed by T cell depletion to increase levels of allochimerism may be mediated by a population which is distinct from that which produces GVHD. These results may have implications for clinical BM transplantation.

  11. Differential effects of protoporphyrin and uroporphyrin on murine mast cells

    SciTech Connect

    Lim, H.W.; Gigli, I.; Wasserman, S.I.

    1987-03-01

    To investigate the mechanisms responsible for the distinct cutaneous manifestations of erythropoietic protoporphyria and porphyria cutanea tarda, the effects of protoporphyrin (PP) and uroporphyrin (URO), the predominant porphyrins in the respective disease, on mast cells were examined. Release of preformed and generated mediators was assessed by the release of radioactivity from cells labeled with (/sup 3/H)serotonin and (/sup 14/C)arachidonic acid, respectively. Clinically relevant doses of PP (25-500 ng/ml) and 396-407 nm irradiation (3-16 X 10(2)J/m2) induced maximal net release of preformed mediators ,f 44.52 +/- 6.6 to 58.01 +/- 4.0% (mean +/- SE). In contrast, irradiation in the presence of URO (50-5000 ng/ml) resulted in less than 5% net release. (3H)Serotonin release induced by PP and irradiation was calcium-independent, and was not enhanced by phorbol 12-myristate 13-acetate, a known activator of protein kinase C. This release was suppressed by catalase, a scavenger of hydrogen peroxide. Furthermore, irradiation in the presence of PP, but not in the presence of URO, resulted in perturbation of cell membrane. Irradiation in the presence of PP also resulted in a maximal net release of generated mediators of 9.98 +/- 3.5% (mean +/- SE), whereas similar treatment in the presence of URO induced less than 0.5% net release. These results suggested that the burning, stinging, erythema, and edema experienced by patients with erythropoietic protoporphyria following sun exposure, and the lack of such findings in patients with porphyria cutanea tarda, may be explained, at least in part, by the differential effects of PP and URO on mast cells.

  12. Martian Arctic Dust Devil and Phoenix Meteorology Mast

    NASA Technical Reports Server (NTRS)

    2008-01-01

    The Surface Stereo Imager on NASA's Phoenix Mars Lander caught this dust devil in action west-southwest of the lander at 11:16 a.m. local Mars time on Sol 104, or the 104th Martian day of the mission, Sept. 9, 2008.

    Dust devils have not been detected in any Phoenix images from earlier in the mission, but at least six were observed in a dozen images taken on Sol 104.

    Dust devils are whirlwinds that often occur when the Sun heats the surface of Mars, or some areas on Earth. The warmed surface heats the layer of atmosphere closest to it, and the warm air rises in a whirling motion, stirring dust up from the surface like a miniature tornado.

    The vertical post near the left edge of this image is the mast of the Meteorological Station on Phoenix. The dust devil visible at the horizon just to the right of the mast is estimated to be 600 to 700 meters (about 2,000 to 2,300 feet) from Phoenix, and 4 to 5 meters (10 to 13 feet) in diameter. It is much smaller than dust devils that have been observed by NASA's Mars Exploration Rover Spirit much closer to the equator. It is closer in size to dust devils seen from orbit in the Phoenix landing region, though still smaller than those.

    The image has been enhanced to make the dust devil easier to see.

    The Phoenix Mission is led by the University of Arizona, Tucson, on behalf of NASA. Project management of the mission is by NASA's Jet Propulsion Laboratory, Pasadena, Calif. Spacecraft development is by Lockheed Martin Space Systems, Denver.

  13. Forskolin inhibits histamine release by neurotensin in the rat perfused hind limb.

    PubMed

    Kérouac, R; St-Pierre, S; Rioux, F

    1984-08-01

    We have assessed the influence of forskolin, a potent activator of adenylate cyclase, on histamine release by neurotensin (NT) in the rat perfused hind limb. The results indicate that forskolin, in concentrations known to increase the cyclic AMP content of various tissues, markedly inhibits the histamine releasing effect of NT. The inhibitory action of forskolin was mimicked by a synthetic cyclic AMP derivative and by 3-isobutyl-1-methyl-xanthine (IBMX), a potent phosphodiesterase inhibitor. Our results suggest that the inhibitory action of forskolin toward histamine release by NT in the rat hind limb mast cells results from the activation of a cyclic AMP-generating system in mast cells.

  14. Multiple bidirectional alterations of phenotype and changes in proliferative potential during the in vitro and in vivo passage of clonal mast cell populations derived from mouse peritoneal mast cells

    SciTech Connect

    Kanakura, Y.; Thompson, H.; Nakano, T.; Yamamura, T.; Asai, H.; Kitamura, Y.; Metcalfe, D.D.; Galli, S.J.

    1988-09-01

    Mouse peritoneal mast cells (PMC) express a connective tissue-type mast cell (CTMC) phenotype, including reactivity with the heparin-binding fluorescent dye berberine sulfate and incorporation of (35S) sulfate predominantly into heparin proteoglycans. When PMC purified to greater than 99% purity were cultured in methylcellulose with IL-3 and IL-4, approximately 25% of the PMC formed colonies, all of which contained both berberine sulfate-positive and berberine sulfate-negative mast cells. When these mast cells were transferred to suspension culture, they generated populations that were 100% berberine sulfate-negative, a characteristic similar to that of mucosal mast cells (MMC), and that synthesized predominantly chondroitin sulfate (35S) proteoglycans. When ''MMC-like'' cultured mast cells derived from WBB6F1-+/+ PMC were injected into the peritoneal cavities of mast cell-deficient WBB6F1-W/Wv mice, the adoptively transferred mast cell population became 100% berberine sulfate-positive. In methylcellulose culture, these ''second generation PMC'' formed clonal colonies containing both berberine sulfate-positive and berberine sulfate-negative cells, but exhibited significantly less proliferative ability than did normal +/+ PMC. Thus, clonal mast cell populations initially derived from single PMC exhibited multiple and bidirectional alterations between CTMC-like and MMC-like phenotypes. However, this process was associated with a progressive diminution of the mast cells' proliferative ability.

  15. The multitasking mast cell: positive and negative roles in the progression of autoimmunity.

    PubMed

    Christy, Alison L; Brown, Melissa A

    2007-09-01

    Among the potential outcomes of an aberrantly functioning immune system are allergic disease and autoimmunity. Although it has been assumed that the underlying mechanisms mediating these conditions are completely different, recent evidence shows that mast cells provide a common link. Mast cells reside in most tissues, are particularly prevalent at sites of Ag entry, and act as sentinel cells of the immune system. They express many inflammatory mediators that affect both innate and adaptive cellular function. They contribute to pathologic allergic inflammation but also serve an important protective role in bacterial and parasite infections. Given the proinflammatory nature of autoimmune responses, it is not surprising that studies using murine models of autoimmunity clearly implicate mast cells in the initiation and/or progression of autoimmune disease. In this review, we discuss the defined and hypothesized mechanisms of mast cell influence on autoimmune diseases, including their surprising and newly discovered role as anti-inflammatory cells.

  16. Human mast cells capture, store, and release bioactive, exogenous IL-17A.

    PubMed

    Noordenbos, Troy; Blijdorp, Iris; Chen, Sijia; Stap, Jan; Mul, Erik; Cañete, Juan D; Lubberts, Erik; Yeremenko, Nataliya; Baeten, Dominique

    2016-09-01

    IL-17A, a major proinflammatory cytokine, can be produced by a variety of leukocytes, but its exact cellular source in human inflammatory diseases remains incompletely understood. IL-17A protein is abundantly found in mast cells in human tissues, such as inflamed synovium, but surprisingly, mechanistic murine studies failed to demonstrate IL-17A production by mast cells. Here, we demonstrate that primary human tissue mast cells do not produce IL-17A themselves but actively capture exogenous IL-17A through receptor-mediated endocytosis. The exogenous IL-17A is stored in intracellular granules and can subsequently be released in a bioactive form. This novel mechanism confers to mast cells the capacity to steer IL-17A-mediated tissue inflammation by the rapid release of preformed cytokine. PMID:27034403

  17. Key regulators control distinct transcriptional programmes in blood progenitor and mast cells

    PubMed Central

    Calero-Nieto, Fernando J; Ng, Felicia S; Wilson, Nicola K; Hannah, Rebecca; Moignard, Victoria; Leal-Cervantes, Ana I; Jimenez-Madrid, Isabel; Diamanti, Evangelia; Wernisch, Lorenz; Göttgens, Berthold

    2014-01-01

    Despite major advances in the generation of genome-wide binding maps, the mechanisms by which transcription factors (TFs) regulate cell type identity have remained largely obscure. Through comparative analysis of 10 key haematopoietic TFs in both mast cells and blood progenitors, we demonstrate that the largely cell type-specific binding profiles are not opportunistic, but instead contribute to cell type-specific transcriptional control, because (i) mathematical modelling of differential binding of shared TFs can explain differential gene expression, (ii) consensus binding sites are important for cell type-specific binding and (iii) knock-down of blood stem cell regulators in mast cells reveals mast cell-specific genes as direct targets. Finally, we show that the known mast cell regulators Mitf and c-fos likely contribute to the global reorganisation of TF binding profiles. Taken together therefore, our study elucidates how key regulatory TFs contribute to transcriptional programmes in several distinct mammalian cell types. PMID:24760698

  18. Beyond apoptosis: The mechanism and function of phosphatidylserine asymmetry in the membrane of activating mast cells

    PubMed Central

    Rysavy, Noel M.; Shimoda, Lori M. N.; Dixon, Alyssa M.; Speck, Mark; Stokes, Alexander J.; Turner, Helen; Umemoto, Eric Y.

    2014-01-01

    Loss of plasma membrane asymmetry is a hallmark of apoptosis, but lipid bilayer asymmetry and loss of asymmetry can contribute to numerous cellular functions and responses that are independent of programmed cell death. Exofacial exposure of phosphatidylserine occurs in lymphocytes and mast cells after antigenic stimulation and in the absence of apoptosis, suggesting that there is a functional requirement for phosphatidylserine exposure in immunocytes. In this review we examine current ideas as to the nature of this functional role in mast cell activation. Mechanistically, there is controversy as to the candidate proteins responsible for phosphatidylserine translocation from the internal to external leaflet, and here we review the candidacies of mast cell PLSCR1 and TMEM16F. Finally we examine the potential relationship between functionally important mast cell membrane perturbations and phosphatidylserine exposure during activation. PMID:25759911

  19. Paul Ehrlich's mastzellen: a historical perspective of relevant developments in mast cell biology.

    PubMed

    Ghably, Jack; Saleh, Hana; Vyas, Harsha; Peiris, Emma; Misra, Niva; Krishnaswamy, Guha

    2015-01-01

    Following the discovery of mast cells (or mastzellen) by the prolific physician researcher, Paul Ehrlich, many advances have improved our understanding of these cells and their fascinating biology. The discovery of immunoglobulin E and receptors for IgE and IgG on mast cells heralded further in vivo and in vitro studies, using molecular technologies and gene knockout models. Mast cells express an array of inflammatory mediators including tryptase, histamine, cytokines, chemokines, and growth factors. They play a role in many varying disease states, from atopic diseases, parasitic infections, hematological malignancies, and arthritis to osteoporosis. This review will attempt to summarize salient evolving areas in mast cell research over the last few centuries that have led to our current understanding of this pivotal multifunctional cell.

  20. Pollen limitation and flower abortion in a wind-pollinated, masting tree.

    PubMed

    Pearse, Ian S; Koenig, Walter D; Funk, Kyle A; Pesendorfer, Mario B

    2015-02-01

    Pollen limitation is a key assumption of theories that explain mast seeding, which is common among wind-pollinated and woody plants. In particular, the pollen coupling hypothesis and pollination Moran effect hypothesis assume pollen limitation as a factor that synchronizes seed crops across individuals. The existence of pollen limitation has not, however, been unambiguously demonstrated in wind-pollinated, masting trees. We conducted a two-year pollen supplementation experiment on a masting oak species, Quercus lobata. Supplemental pollen increased acorn set in one year but not in the other, supporting the importance of pollen coupling and pollination Moran effect models of mast seeding. We also tracked the fate of female flowers over five years and found that the vast majority of flowers were aborted for reasons unrelated to pollination, even in the presence of excess pollen. Pollen limitation can reduce annual seed set in a wind-pollinated tree, but factors other than pollen limitation cause the majority of flower abortion.

  1. Dengue Virus Infection of Mast Cells Triggers Endothelial Cell Activation ▿

    PubMed Central

    Brown, Michael G.; Hermann, Laura L.; Issekutz, Andrew C.; Marshall, Jean S.; Rowter, Derek; Al-Afif, Ayham; Anderson, Robert

    2011-01-01

    Vascular perturbation is a hallmark of severe forms of dengue disease. We show here that antibody-enhanced dengue virus infection of primary human cord blood-derived mast cells (CBMCs) and the human mast cell-like line HMC-1 results in the release of factor(s) which activate human endothelial cells, as evidenced by increased expression of the adhesion molecules ICAM-1 and VCAM-1. Endothelial cell activation was prevented by pretreatment of mast cell-derived supernatants with a tumor necrosis factor (TNF)-specific blocking antibody, thus identifying TNF as the endothelial cell-activating factor. Our findings suggest that mast cells may represent an important source of TNF, promoting vascular endothelial perturbation following antibody-enhanced dengue virus infection. PMID:21068256

  2. Emerging Role of Mast Cells and Macrophages in Cardiovascular and Metabolic Diseases

    PubMed Central

    Xu, Jia-Ming

    2012-01-01

    Mast cells are essential in allergic immune responses. Recent discoveries have revealed their direct participation in cardiovascular diseases and metabolic disorders. Although more sophisticated mechanisms are still unknown, data from animal studies suggest that mast cells act similarly to macrophages and other inflammatory cells and contribute to human diseases through cell–cell interactions and the release of proinflammatory cytokines, chemokines, and proteases to induce inflammatory cell recruitment, cell apoptosis, angiogenesis, and matrix protein remodeling. Reduced cardiovascular complications and improved metabolic symptoms in animals receiving over-the-counter antiallergy medications that stabilize mast cells open another era of mast cell biology and bring new hope to human patients suffering from these conditions. PMID:22240242

  3. 14. Hold, port side,looking forward to mast and strongback, centerboard ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    14. Hold, port side,looking forward to mast and strongback, centerboard trunk to starboard. - Two-Sail Bateau E. C. COLLIER, Chesapeake Bay Maritime Museum, Mills Street, Saint Michaels, Talbot County, MD

  4. Development of a continuous manufacturing method for a CFRP collapsible tube mast

    NASA Astrophysics Data System (ADS)

    Bowen, D. H.; Davidson, R.; Lee, R. J.; Thorpe, T.

    1986-06-01

    A sequential molding process was developed for forming continuous lengths of profiled carbon fiber reinforced plastic (CFRP) sheet, and for the edge-bonding of two identical profiles to produce a lenticular-shaped collapsible tube mast (CTM). The process was designed to enable a wide range of CTM sizes, characterized by the shape radius r, to be produced, and it will accept either thermosetting or thermoplastic matrix composites. The Tube Manufacturing Method (TMM) was proved by the construction of a laboratory scale rig and its use to produce continuously 10 m lengths of mast profile of uniform section and surface finish. The mechanical properties of the fabrics impregnated with the two resins were measured to provide basic tube mast design data. Viscoelastic relaxations in both types of composites were determined after storing sections of mast profile in the flattened condition over periods of time as a function of temperature.

  5. Involvement of mast cells and proteinase-activated receptor 2 in oxaliplatin-induced mechanical allodynia in mice.

    PubMed

    Sakamoto, Ayumi; Andoh, Tsugunobu; Kuraishi, Yasushi

    2016-03-01

    The chemotherapeutic agent oxaliplatin induces neuropathic pain, a dose-limiting side effect, but the underlying mechanisms are not fully understood. Here, we show the potential involvement of cutaneous mast cells in oxaliplatin-induced mechanical allodynia in mice. A single intraperitoneal injection of oxaliplatin induced mechanical allodynia, which peaked on day 10 after injection. Oxaliplatin-induced mechanical allodynia was almost completely prevented by congenital mast cell deficiency. The numbers of total and degranulated mast cells was significantly increased in the skin after oxaliplatin administration. Repetitive topical application of the mast cell stabilizer azelastine hydrochloride inhibited mechanical allodynia and the degranulation of mast cells without affecting the number of mast cells in oxaliplatin-treated mice. The serine protease inhibitor camostat mesilate and the proteinase-activated receptor 2 (PAR2) antagonist FSLLRY-NH2 significantly inhibited oxaliplatin-induced mechanical allodynia. However, it was not inhibited by the H1 histamine receptor antagonist terfenadine. Single oxaliplatin administration increased the activity of cutaneous serine proteases, which was attenuated by camostat and mast cell deficiency. Depletion of the capsaicin-sensitive primary afferents by neonatal capsaicin treatment almost completely prevented oxaliplatin-induced mechanical allodynia, the increase in the number of mast cells, and the activity of cutaneous serine proteases. These results suggest that serine protease(s) released from mast cells and PAR2 are involved in oxaliplatin-induced mechanical allodynia. Therefore, oxaliplatin may indirectly affect the functions of mast cells through its action on capsaicin-sensitive primary afferents.

  6. Involvement of mast cells and proteinase-activated receptor 2 in oxaliplatin-induced mechanical allodynia in mice.

    PubMed

    Sakamoto, Ayumi; Andoh, Tsugunobu; Kuraishi, Yasushi

    2016-03-01

    The chemotherapeutic agent oxaliplatin induces neuropathic pain, a dose-limiting side effect, but the underlying mechanisms are not fully understood. Here, we show the potential involvement of cutaneous mast cells in oxaliplatin-induced mechanical allodynia in mice. A single intraperitoneal injection of oxaliplatin induced mechanical allodynia, which peaked on day 10 after injection. Oxaliplatin-induced mechanical allodynia was almost completely prevented by congenital mast cell deficiency. The numbers of total and degranulated mast cells was significantly increased in the skin after oxaliplatin administration. Repetitive topical application of the mast cell stabilizer azelastine hydrochloride inhibited mechanical allodynia and the degranulation of mast cells without affecting the number of mast cells in oxaliplatin-treated mice. The serine protease inhibitor camostat mesilate and the proteinase-activated receptor 2 (PAR2) antagonist FSLLRY-NH2 significantly inhibited oxaliplatin-induced mechanical allodynia. However, it was not inhibited by the H1 histamine receptor antagonist terfenadine. Single oxaliplatin administration increased the activity of cutaneous serine proteases, which was attenuated by camostat and mast cell deficiency. Depletion of the capsaicin-sensitive primary afferents by neonatal capsaicin treatment almost completely prevented oxaliplatin-induced mechanical allodynia, the increase in the number of mast cells, and the activity of cutaneous serine proteases. These results suggest that serine protease(s) released from mast cells and PAR2 are involved in oxaliplatin-induced mechanical allodynia. Therefore, oxaliplatin may indirectly affect the functions of mast cells through its action on capsaicin-sensitive primary afferents. PMID:26804251

  7. Live Staphylococcus aureus Induces Expression and Release of Vascular Endothelial Growth Factor in Terminally Differentiated Mouse Mast Cells.

    PubMed

    Johnzon, Carl-Fredrik; Rönnberg, Elin; Guss, Bengt; Pejler, Gunnar

    2016-01-01

    Mast cells have been shown to express vascular endothelial growth factor (VEGF), thereby implicating mast cells in pro-angiogenic processes. However, the mechanism of VEGF induction in mast cells and the possible expression of VEGF in fully mature mast cells have not been extensively studied. Here, we report that terminally differentiated peritoneal cell-derived mast cells can be induced to express VEGF in response to challenge with Staphylococcus aureus, thus identifying a mast cell-bacteria axis as a novel mechanism leading to VEGF release. Whereas live bacteria produced a robust upregulation of VEGF in mast cells, heat-inactivated bacteria failed to do so, and bacteria-conditioned media did not induce VEGF expression. The induction of VEGF was not critically dependent on direct cell-cell contact between bacteria and mast cells. Hence, these findings suggest that VEGF can be induced by soluble factors released during the co-culture conditions. Neither of a panel of bacterial cell-wall products known to activate toll-like receptor (TLR) signaling promoted VEGF expression in mast cells. In agreement with the latter, VEGF induction occurred independently of Myd88, an adaptor molecule that mediates the downstream events following TLR engagement. The VEGF induction was insensitive to nuclear factor of activated T-cells inhibition but was partly dependent on the nuclear factor kappa light-chain enhancer of activated B cells signaling pathway. Together, these findings identify bacterial challenge as a novel mechanism by which VEGF is induced in mast cells. PMID:27446077

  8. Mast cells in common wolffish Anarhichas lupus L.: ontogeny, distribution and association with lymphatic vessels.

    PubMed

    Hellberg, Hege; Bjerkås, Inge; Vågnes, Øyvind B; Noga, Edward J

    2013-12-01

    The morphology, ontogeny and tissue distribution of mast cells were studied in common wolffish(Anarhichas lupus L.) at the larval, juvenile and adult life stages using light and electron-microscopy and immunohistochemistry. Fish were sampled at 1 day, 1, 2, 3, 4, 8 and 12 weeks post-hatching in addition to 6 and 9 months and 2 years and older. From 8 weeks post-hatching, mast cells in common wolffish mainly appeared as oval or rounded cells 8-15 mm in diameter with an eccentrically placed, ovoid nucleus and filled with cytoplasmic granules up to 1.2 mm in diameter. Granules were refractile and eosinophilic to slightly basophilic in H&E and stained bright red with Martius-scarlet-blue and purple with pinacyanol erythrosinate in formalin-fixed tissues. Mast cells stained positive for piscidin 4 and Fc ε RI by immunohistochemistry. From 1 day to 4 weeks post-hatching, immature mast cell containing only a few irregularly sized cytoplasmic granules were observed by light and electron-microscopy in loose connective tissue of cranial areas. From 1 day post-hatching, these cells stained positive for piscidin 4 and Fc ε RI by immunohistochemistry. From 12 weeks post-hatching, mast cells showed a primarily perivascular distribution and were particularly closely associated with lymphatic vessels and sinuses. Mast cells were mainly located at the peripheral border of the adventitia of arteries and veins, while they were in intimate contact with the endothelium of the lymphatic vessels. Numerous mast cells were observed in the intestine. A stratum compactum, as described in salmonids, was not observed in wolffish intestine,nor were mast cells confined to a separate layer, a stratum granulosum. Lymphatic vessels consisting of endothelium, intimal connective tissue and a poorly developed basal lamina were observed in the intestine. Scanning electron microscopy was used to compare the structure and localization of intestinal mast cells of common wolffish and rainbow trout

  9. Critical role of tissue mast cells in controlling long-term glucose sensor function in vivo.

    PubMed

    Klueh, Ulrike; Kaur, Manjot; Qiao, Yi; Kreutzer, Donald L

    2010-06-01

    Little is known about the specific cells, mediators and mechanisms involved in the loss of glucose sensor function (GSF) in vivo. Since mast cells (MC) are known to be key effector cells in inflammation and wound healing, we hypothesized that MC and their products are major contributors to the skin inflammation and wound healing that controls GSF at sites of sensor implantation. To test this hypothesis we utilized a murine model of continuous glucose monitoring (CGM) in vivo in both normal C57BL/6 mice (mast cell sufficient), as well as mast cell deficient B6.Cg-Kit(W-sh)/HNihrJaeBsmJ (Sash) mice over a 28 day CGM period. As expected, both strains of mice displayed excellent CGM for the first 7 days post sensor implantation (PSI). CGM in the mast cell sufficient C57BL/6 mice was erratic over the remaining 21 days PSI. CGM in the mast cell deficient Sash mice displayed excellent sensor function for the entire 28 day of CGM. Histopathologic evaluation of implantation sites demonstrated that tissue reactions in Sash mice were dramatically less compared to the reactions in normal C57BL/6 mice. Additionally, mast cells were also seen to be consistently associated with the margins of sensor tissue reactions in normal C57BL/6 mice. Finally, direct injection of bone marrow derived mast cells at sites of sensor implantation induced an acute and dramatic loss of sensor function in both C57BL/6 and Sash mice. These results demonstrate the key role of mast cells in controlling glucose sensor function in vivo. PMID:20226521

  10. Innervation of enteric mast cells by primary spinal afferents in guinea pig and human small intestine.

    PubMed

    Wang, Guo-Du; Wang, Xi-Yu; Liu, Sumei; Qu, Meihua; Xia, Yun; Needleman, Bradley J; Mikami, Dean J; Wood, Jackie D

    2014-10-01

    Mast cells express the substance P (SP) neurokinin 1 receptor and the calcitonin gene-related peptide (CGRP) receptor in guinea pig and human small intestine. Enzyme-linked immunoassay showed that activation of intramural afferents by antidromic electrical stimulation or by capsaicin released SP and CGRP from human and guinea pig intestinal segments. Electrical stimulation of the afferents evoked slow excitatory postsynaptic potentials (EPSPs) in the enteric nervous system. The slow EPSPs were mediated by tachykinin neurokinin 1 and CGRP receptors. Capsaicin evoked slow EPSP-like responses that were suppressed by antagonists for protease-activated receptor 2. Afferent stimulation evoked slow EPSP-like excitation that was suppressed by mast cell-stabilizing drugs. Histamine and mast cell protease II were released by 1) exposure to SP or CGRP, 2) capsaicin, 3) compound 48/80, 4) elevation of mast cell Ca²⁺ by ionophore A23187, and 5) antidromic electrical stimulation of afferents. The mast cell stabilizers cromolyn and doxantrazole suppressed release of protease II and histamine when evoked by SP, CGRP, capsaicin, A23187, electrical stimulation of afferents, or compound 48/80. Neural blockade by tetrodotoxin prevented mast cell protease II release in response to antidromic electrical stimulation of mesenteric afferents. The results support a hypothesis that afferent innervation of enteric mast cells releases histamine and mast cell protease II, both of which are known to act in a diffuse paracrine manner to influence the behavior of enteric nervous system neurons and to elevate the sensitivity of spinal afferent terminals.

  11. Incidence of Mast Cells in Gingival and Periapical Inflammation- A Kaleidoscopic Study

    PubMed Central

    Sreedhar, Gadiputi; George, Jiji

    2016-01-01

    Introduction Mast cells are large granular cells that have classically been related to neutrophil stimulation during early step of inflammation. Aim The objective of this work was to identify the incidence of mast cells in inflammatory lesions like periapical granuloma, pyogenic granuloma, gingival hyperplasia. 1. To assess the staining intensity of mast cells by using different metachromatic stains. 2. To correlate the above findings histopathologically. Materials and Methods In this study, we used 5 micron thick sections from paraffin-embedded tissue blocks of previously diagnosed periapical and gingival inflammatory lesions. The sections were stained with routine H & E and metachromatic stains like Toluidine blue, Alcian blue, Aldehyde fuchsin and Giemsa. The number of mast cells was quantified. Statistical analysis was done and mast cell numbers were compared. Results In both gingival and periapical inflammatory lesions, toludine blue showed more number of mast cells followed by giemsa. Giemsa stain showed statistical significance in differentiating both periapical and gingival lesions (p<0.05) in terms of mast cell count. Moderate inflammation (46.4%) was seen in a higher propotion of gingival inflammations whereas periapical inflammatory lesions revealed severe inflammation (53.3%). In both types of inflammatory lesions, higher staining intensity was shown by toludine blue followed by giemsa which was statistically significant. Conclusion Mast cell number is inversely proportional to inflammatory response in gingival inflammatory lesions and directly proportional to inflammatory response in periapical inflammatory lesions. Although, toludine blue is found to be a better stain, giemsa has equivalent properties as that of toludine blue. PMID:27437338

  12. Mast cells modulate acute ozone-induced inflammation of the murine lung

    SciTech Connect

    Kleeberger, S.R.; Seiden, J.E.; Levitt, R.C.; Zhang, L.Y. )

    1993-11-01

    We hypothesized that mast cells modulate lung inflammation that develops after acute ozone (O3) exposure. Two tests were done: (1) genetically mast-cell-deficient (WBB6F1-W/Wv, WCB6F1-SI/SId) and bone-marrow-transplanted W/Wv mice were exposed to O3 or filtered air, and the inflammatory responses were compared with those of mast-cell-sufficient congenic mice (WBB6F1-(+)/+, WCB6F1-(+)/+); (2) genetically O3-susceptible C57BL/6J mice were treated pharmacologically with putative mast-cell modulators or vehicle, and the O3-induced inflammatory responses were compared. Mice were exposed to 1.75 ppm O3 or air for 3 h, and lung inflammation was assessed by bronchoalveolar lavage (BAL) 6 and 24 h after exposure. Relative to O3-exposed W/Wv and SI/SId mice, the mean numbers of lavageable polymorphonuclear leukocytes (PMNs) and total BAL protein concentration (a marker of permeability) were significantly greater in the respective O3-exposed normal congenic +/+ mice (p < 0.05). Mast cells were reconstituted in W/Wv mice by transplantation of bone marrow cells from congenic +/+ mice, and O3-induced lung inflammation was assessed in the mast-cell-replete W/Wv mice. After O3 exposure, the changes in lavageable PMNs and total protein of mast-cell-replete W/Wv mice were not different from age-matched normal +/+ control mice, and they were significantly greater than those of sham-transplanted W/Wv mice (p < 0.05). Genetically susceptible C57BL/6J mice were pretreated with a mast-cell stabilizer (nedocromil sodium), secretagogue (compound 48/80), or vehicle, and the mice were exposed to O3.

  13. Environmental Estrogens Induce Mast Cell Degranulation and Enhance IgE-Mediated Release of Allergic Mediators

    PubMed Central

    Narita, Shin-ichiro; Goldblum, Randall M.; Watson, Cheryl S.; Brooks, Edward G.; Estes, D. Mark; Curran, Edward M.; Midoro-Horiuti, Terumi

    2007-01-01

    Background Prevalence and morbidity of allergic diseases have increased over the last decades. Based on the recently recognized differences in asthma prevalence between the sexes, we have examined the effect of endogenous estrogens on a key element of the allergic response. Some lipophilic pollutants have estrogen-like activities and are termed environmental estrogens. These pollutants tend to degrade slowly in the environment and to bioaccumulate and bioconcentrate in the food chain; they also have long biological half-lives. Objectives Our goal in this study was to identify possible pathogenic roles for environmental estrogens in the development of allergic diseases. Methods We screened a number of environmental estrogens for their ability to modulate the release of allergic mediators from mast cells. We incubated a human mast cell line and primary mast cell cultures derived from bone marrow of wild type and estrogen receptor α (ER-α )–deficient mice with environmental estrogens with and without estradiol or IgE and allergens. We assessed degranulation of mast cells by quantifying the release of β -hexosaminidase. Results All of the environmental estrogens tested caused rapid, dose-related release of β -hexosaminidase from mast cells and enhanced IgE-mediated release. The combination of physiologic concentrations of 17β -estradiol and several concentrations of environmental estrogens had additive effects on mast cell degranulation. Comparison of bone marrow mast cells from ER-α –sufficient and ER-α –deficient mice indicated that much of the effect of environmental estrogens was mediated by ER-α . Conclusions Our findings suggest that estrogenic environmental pollutants might promote allergic diseases by inducing and enhancing mast cell degranulation by physiologic estrogens and exposure to allergens. PMID:17366818

  14. Brain mast cells link the immune system to anxiety-like behavior.

    PubMed

    Nautiyal, Katherine M; Ribeiro, Ana C; Pfaff, Donald W; Silver, Rae

    2008-11-18

    Mast cells are resident in the brain and contain numerous mediators, including neurotransmitters, cytokines, and chemokines, that are released in response to a variety of natural and pharmacological triggers. The number of mast cells in the brain fluctuates with stress and various behavioral and endocrine states. These properties suggest that mast cells are poised to influence neural systems underlying behavior. Using genetic and pharmacological loss-of-function models we performed a behavioral screen for arousal responses including emotionality, locomotor, and sensory components. We found that mast cell deficient Kit(W-sh/W-sh) (sash(-/-)) mice had a greater anxiety-like phenotype than WT and heterozygote littermate control animals in the open field arena and elevated plus maze. Second, we show that blockade of brain, but not peripheral, mast cell activation increased anxiety-like behavior. Taken together, the data implicate brain mast cells in the modulation of anxiety-like behavior and provide evidence for the behavioral importance of neuroimmune links. PMID:19004805

  15. Mast Cells and Influenza A Virus: Association with Allergic Responses and Beyond

    PubMed Central

    Graham, Amy C.; Temple, Rachel M.; Obar, Joshua J.

    2015-01-01

    Influenza A virus (IAV) is a widespread infectious agent commonly found in mammalian and avian species. In humans, IAV is a respiratory pathogen that causes seasonal infections associated with significant morbidity in young and elderly populations, and has a large economic impact. Moreover, IAV has the potential to cause both zoonotic spillover infection and global pandemics, which have significantly greater morbidity and mortality across all ages. The pathology associated with these pandemic and spillover infections appear to be the result of an excessive inflammatory response leading to severe lung damage, which likely predisposes the lungs for secondary bacterial infections. The lung is protected from pathogens by alveolar epithelial cells, endothelial cells, tissue resident alveolar macrophages, dendritic cells, and mast cells. The importance of mast cells during bacterial and parasitic infections has been extensively studied; yet, the role of these hematopoietic cells during viral infections is only beginning to emerge. Recently, it has been shown that mast cells can be directly activated in response to IAV, releasing mediators such histamine, proteases, leukotrienes, inflammatory cytokines, and antiviral chemokines, which participate in the excessive inflammatory and pathological response observed during IAV infections. In this review, we will examine the relationship between mast cells and IAV, and discuss the role of mast cells as a potential drug target during highly pathological IAV infections. Finally, we proposed an emerging role for mast cells in other viral infections associated with significant host pathology. PMID:26042121

  16. The granzyme B inhibitor proteinase inhibitor 9 (PI9) is expressed by human mast cells.

    PubMed

    Bladergroen, Bellinda A; Strik, Merel C M; Wolbink, Angela M; Wouters, Dorine; Broekhuizen, Roel; Kummer, J Alain; Hack, C Erik

    2005-04-01

    The activity of granzyme B, a main effector molecule of cytotoxic T lymphocytes (CTL) and natural killer cells, is regulated by the human intracellular serpin proteinase inhibitor 9 (PI9). This inhibitor is particularly expressed by CTL and dendritic cells, in which it serves to protect these cells against endogenous and locally released granzyme B. Moreover, PI9 expression by neoplastic cells may constitute one of the mechanisms for tumors to escape immune surveillance. Here we show that PI9 is also expressed by human mast cells. In immunohistochemical studies using a PI9-specific monoclonal antibody, strong cytoplasmic staining for PI9 was found in normal mast cells in various tissues throughout the body. In addition, in 80% of all cases of cutaneous and systemic mastocytosis tested the majority of the mast cells expressed PI9. As an in vitro model for PI9 expression by mast cells, we studied expression by the human mast cell line HMC-1. Stimulation of HMC-1 with PMA and the calcium ionophore A23187 resulted in a marked increase of PI9 expression. Thus, PI9 is expressed by activated mast cells. We suggest that this expression serves to protect these cells against apoptosis induced by granzyme B released during initiation of the local inflammatory response.

  17. Mast cell degranulation by a hemolytic lipid toxin decreases GBS colonization and infection

    PubMed Central

    Gendrin, Claire; Vornhagen, Jay; Ngo, Lisa; Whidbey, Christopher; Boldenow, Erica; Santana-Ufret, Veronica; Clauson, Morgan; Burnside, Kellie; Galloway, Dionne P.; Waldorf, Kristina Adams; Piliponsky, Adrian M.; Rajagopal, Lakshmi

    2015-01-01

    Ascending infection of microbes from the lower genital tract into the amniotic cavity increases the risk of preterm birth, stillbirth, and newborn infections. Host defenses that are critical for preventing ascending microbial infection are not completely understood. Group B Streptococcus (GBS) are Gram-positive bacteria that frequently colonize the lower genital tract of healthy women but cause severe infections during pregnancy, leading to preterm birth, stillbirth, or early-onset newborn infections. We recently described that the GBS pigment is hemolytic, and increased pigment expression promotes GBS penetration of human placenta. Here, we show that the GBS hemolytic pigment/lipid toxin and hyperpigmented GBS strains induce mast cell degranulation, leading to the release of preformed and proinflammatory mediators. Mast cell–deficient mice exhibit enhanced bacterial burden, decreased neutrophil mobilization, and decreased immune responses during systemic GBS infection. In a vaginal colonization model, hyperpigmented GBS strains showed increased persistence in mast cell–deficient mice compared to mast cell–proficient mice. Consistent with these observations, fewer rectovaginal GBS isolates from women in their third trimester of pregnancy were hyperpigmented/hyperhemolytic. Our work represents the first example of a bacterial hemolytic lipid that induces mast cell degranulation and emphasizes the role of mast cells in limiting genital colonization by hyperpigmented GBS. PMID:26425734

  18. Brain mast cells link the immune system to anxiety-like behavior

    PubMed Central

    Nautiyal, Katherine M.; Ribeiro, Ana C.; Pfaff, Donald W.; Silver, Rae

    2008-01-01

    Mast cells are resident in the brain and contain numerous mediators, including neurotransmitters, cytokines, and chemokines, that are released in response to a variety of natural and pharmacological triggers. The number of mast cells in the brain fluctuates with stress and various behavioral and endocrine states. These properties suggest that mast cells are poised to influence neural systems underlying behavior. Using genetic and pharmacological loss-of-function models we performed a behavioral screen for arousal responses including emotionality, locomotor, and sensory components. We found that mast cell deficient KitW−sh/W−sh (sash−/−) mice had a greater anxiety-like phenotype than WT and heterozygote littermate control animals in the open field arena and elevated plus maze. Second, we show that blockade of brain, but not peripheral, mast cell activation increased anxiety-like behavior. Taken together, the data implicate brain mast cells in the modulation of anxiety-like behavior and provide evidence for the behavioral importance of neuroimmune links. PMID:19004805

  19. Inhibition of tryptase release from human colon mast cells by histamine receptor antagonists.

    PubMed

    He, Shao-Heng; Xie, Hua; Fu, Yi-Ling

    2005-03-01

    The main objective of this study was to investigate the ability of histamine receptor antagonists to modulate tryptase release from human colon mast cells induced by histamine. Enzymatically dispersed cells from human colon were challenged with histamine in the absence or presence of the histamine receptor antagonists, and the tryptase release was determined. It was found that histamine induced tryptase release from colon mast cells was inhibited by up to approximately 61.5% and 24% by the H1 histamine receptor antagonist terfenadine and the H2 histamine receptor antagonist cimetidine, respectively, when histamine and its antagonists were added to cells at the same time. The H3 histamine receptor antagonist clobenpropit had no effect on histamine induced tryptase release from colon mast cells at all concentrations tested. Preincubation of terfenadine, cimetidine or clobenpropit with cells for 20 minutes before challenging with histamine did not enhance the ability of these antihistamines to inhibit histamine induced tryptase release. Apart from terfenadine at 100 microg/ml, the antagonists themselves did not stimulate tryptase release from colon mast cells following both 15 minutes and 35 minutes incubation periods. It was concluded that H1 and H2 histamine receptor antagonists were able to inhibit histamine induced tryptase release from colon mast cells. This not only added some new data to our hypothesis of self-amplification mechanisms of mast cell degranulation, but also suggested that combining these two types of antihistamine drugs could be useful for the treatment of inflammatory bowel disease (IBD).

  20. Regulation of GATA Factor Expression Is Distinct between Erythroid and Mast Cell Lineages

    PubMed Central

    Ohmori, Shin'ya; Takai, Jun; Ishijima, Yasushi; Suzuki, Mikiko; Moriguchi, Takashi; Philipsen, Sjaak; Yamamoto, Masayuki

    2012-01-01

    The zinc finger transcription factors GATA1 and GATA2 participate in mast cell development. Although the expression of these factors is regulated in a cell lineage-specific and differentiation stage-specific manner, their regulation during mast cell development has not been clarified. Here, we show that the GATA2 mRNA level was significantly increased while GATA1 was maintained at low levels during the differentiation of mast cells derived from mouse bone marrow (BMMCs). Unlike in erythroid cells, forced expression or small interfering RNA (siRNA)-mediated knockdown of GATA1 rarely affected GATA2 expression, and vice versa, in mast cells, indicating the absence of cross-regulation between Gata1 and Gata2 genes. Chromatin immunoprecipitation assays revealed that both GATA factors bound to most of the conserved GATA sites of Gata1 and Gata2 loci in BMMCs. However, the GATA1 hematopoietic enhancer (G1HE) of the Gata1 gene, which is essential for GATA1 expression in erythroid and megakaryocytic lineages, was bound only weakly by both GATA factors in BMMCs. Furthermore, transgenic-mouse reporter assays revealed that the G1HE is not essential for reporter expression in BMMCs and peritoneal mast cells. Collectively, these results demonstrate that the expression of GATA factors in mast cells is regulated in a manner quite distinct from that in erythroid cells. PMID:22988301

  1. Mast cell activation contributes to sickle cell pathobiology and pain in mice

    PubMed Central

    Vincent, Lucile; Vang, Derek; Nguyen, Julia; Gupta, Mihir; Luk, Kathryn; Ericson, Marna E.; Simone, Donald A.

    2013-01-01

    Sickle cell anemia (SCA) is an inherited disorder associated with severe lifelong pain and significant morbidity. The mechanisms of pain in SCA remain poorly understood. We show that mast cell activation/degranulation contributes to sickle pain pathophysiology by promoting neurogenic inflammation and nociceptor activation via the release of substance P in the skin and dorsal root ganglion. Mast cell inhibition with imatinib ameliorated cytokine release from skin biopsies and led to a correlative decrease in granulocyte-macrophage colony-stimulating factor and white blood cells in transgenic sickle mice. Targeting mast cells by genetic mutation or pharmacologic inhibition with imatinib ameliorates tonic hyperalgesia and prevents hypoxia/reoxygenation-induced hyperalgesia in sickle mice. Pretreatment with the mast cell stabilizer cromolyn sodium improved analgesia following low doses of morphine that were otherwise ineffective. Mast cell activation therefore underlies sickle pathophysiology leading to inflammation, vascular dysfunction, pain, and requirement for high doses of morphine. Pharmacological targeting of mast cells with imatinib may be a suitable approach to address pain and perhaps treat SCA. PMID:23775718

  2. Optical imaging of fibrin deposition to elucidate participation of mast cells in foreign body responses

    PubMed Central

    Weng, Hong; Tang, Ewin N.; Baker, David W.; Tang, Liping

    2014-01-01

    Mast cell activation has been shown to be an initiator and a key determinant of foreign body reactions. However, there is no non-invasive method that can quantify the degree of implant-associated mast cell activation. Taking advantage of the fact that fibrin deposition is a hallmark of mast cell activation around biomaterial implants, a near infrared probe was fabricated to have high affinity to fibrin. Subsequent in vitro testing confirmed that this probe has high affinity to fibrin. Using a subcutaneous particle implantation model, we found significant accumulation of fibrin-affinity probes at the implant sites as early as 15 min following particle implantation. The accumulation of fibrin-affinity probes at the implantation sites could also be substantially reduced if anti-coagulant – heparin was administered at the implant sites. Further studies have shown that subcutaneous administration of mast cell activator – compound 48/80 – prompted the accumulation of fibrin-affinity probes. However, implant-associated fibrin-affinity probe accumulation was substantially reduced in mice with mast cell deficiency. The results show that our fibrin-affinity probes may serve as a powerful tool to monitor and measure the extent of biomaterial-mediated fibrin deposition and mast cell activation in vivo. PMID:24342726

  3. Quantification of mast cells and blood vessels in the skin of patients with cutaneous mucinosis.

    PubMed

    Martins, Clarice; Nascimento, Adriana Paulino; Monte-Alto-Costa, Andréa; Alves, Maria de Fátima Scotelaro; Carneiro, Sueli Coelho; Porto, Luís Cristóvão de Moraes Sobrino

    2010-07-01

    Recent studies have suggested that mast cell numbers are increased in the skin of patients with cutaneous mucinosis and that these cells may have an important role in angiogenesis and production of mucin. Then, skin biopsies from 30 patients with cutaneous mucinosis (papular mucinosis, focal mucinosis, and mucinosis associated with lupus erythematosus) and from 10 healthy subjects were analyzed. Mast cells and blood vessels were immunolabeled with anti-tryptase and anti-CD34 antibodies, respectively, and then quantified stereologically. Counting was performed in papillary and reticular dermis. An increase in the number of mast cells was observed in the skin of patients with cutaneous mucinosis compared with the control group. Only minimal differences were observed in vessel stereology. There was no correlation between the increase in the number of mast cells and the number of blood vessels in the patients studied. There was no significant difference in the numbers of mast cells or blood vessels between the 3 subgroups of cutaneous mucinosis. Although many clinical forms of mucinosis have been described, neither mast cell number nor vessel distribution seems to distinguish the 3 different forms studied here.

  4. Mast cells in renal inflammation and fibrosis: lessons learnt from animal studies.

    PubMed

    Madjene, Lydia Celia; Pons, Maguelonne; Danelli, Luca; Claver, Julien; Ali, Liza; Madera-Salcedo, Iris K; Kassas, Asma; Pellefigues, Christophe; Marquet, Florian; Dadah, Albert; Attout, Tarik; El-Ghoneimi, Alaa; Gautier, Gregory; Benhamou, Marc; Charles, Nicolas; Daugas, Eric; Launay, Pierre; Blank, Ulrich

    2015-01-01

    Mast cells are hematopoietic cells involved in inflammation and immunity and have been recognized also as important effector cells in kidney inflammation. In humans, only a few mast cells reside in kidneys constitutively but in progressive renal diseases their numbers increase substantially representing an essential part of the interstitial infiltrate of inflammatory cells. Recent data obtained in experimental animal models have emphasized a complex role of these cells and the mediators they release as they have been shown both to promote, but also to protect from disease and fibrosis development. Sometimes conflicting results have been reported in similar models suggesting a very narrow window between these activities depending on the pathophysiological context. Interestingly in mice, mast cell or mast cell mediator specific actions became also apparent in the absence of significant mast cell kidney infiltration supporting systemic or regional actions via draining lymph nodes or kidney capsules. Many of their activities rely on the capacity of mast cells to release, in a timely controlled manner, a wide range of inflammatory mediators, which can promote anti-inflammatory actions and repair activities that contribute to healing, but in some circumstances or in case of inappropriate regulation may also promote kidney disease.

  5. Nanoimaging granule dynamics and subcellular structures in activated mast cells using soft X-ray tomography

    PubMed Central

    Chen, Huan-Yuan; Chiang, Dapi Meng-Lin; Lin, Zi-Jing; Hsieh, Chia-Chun; Yin, Gung-Chian; Weng, I.-Chun; Guttermann, Peter; Werner, Stephan; Henzler, Katja; Schneider, Gerd; Lai, Lee-Jene; Liu, Fu-Tong

    2016-01-01

    Mast cells play an important role in allergic responses. During activation, these cells undergo degranulation, a process by which various kinds of mediators stored in the granules are released. Granule homeostasis in mast cells has mainly been studied by electron microscopy (EM), where the fine structures of subcellular organelles are partially destroyed during sample preparation. Migration and fusion of granules have not been studied in detail in three dimensions (3D) in unmodified samples. Here, we utilized soft X-ray tomography (SXT) coupled with fluorescence microscopy to study the detailed structures of organelles during mast cell activation. We observed granule fission, granule fusion to plasma membranes, and small vesicles budding from granules. We also detected lipid droplets, which became larger and more numerous as mast cells were activated. We observed dramatic morphological changes of mitochondria in activated mast cells and 3D-reconstruction revealed the highly folded cristae inner membrane, features of functionally active mitochondria. We also observed giant vesicles containing granules, mitochondria, and lipid droplets, which we designated as granule-containing vesicles (GCVs) and verified their presence by EM in samples prepared by cryo-substitution, albeit with a less clear morphology. Thus, our studies using SXT provide significant insights into mast cell activation at the organelle level. PMID:27748356

  6. Impaired expression of the mitochondrial calcium uniporter suppresses mast cell degranulation.

    PubMed

    Furuno, Tadahide; Shinkai, Narumi; Inoh, Yoshikazu; Nakanishi, Mamoru

    2015-12-01

    Calcium ion (Ca(2+)) uptake into the mitochondrial matrix influences ATP production, Ca(2+) homeostasis, and apoptosis regulation. Ca(2+) uptake across the ion-impermeable inner mitochondrial membrane is mediated by the mitochondrial Ca(2+) uniporter (MCU) complex. The MCU complex forms a pore structure composed of several proteins. MCU is a Ca(2+)-selective channel in the inner-mitochondrial membrane that allows electrophoretic Ca(2+) entry into the matrix. Mitochondrial Ca(2+) uptake 1 (MICU1) functions as a Ca(2+)-sensing regulator of the MCU complex. Previously, by microscopic analysis at the single-cell level, we found that during mast cell activation, mitochondria capture cytosolic Ca(2+) in two steps. Consequently, mitochondrial Ca(2+) uptake likely plays a role in cellular function through cytosolic Ca(2+) buffering. Here, we investigate the role of MCU and MICU1 in mitochondrial Ca(2+) uptake and mast cell degranulation using MCU- and MICU1-knockdown (KD) mast cells. Whereas MCU- and MICU1-KD mast cells show normal proliferation rates and mitochondrial membrane potential, they exhibit slow and reduced cytosolic and mitochondrial Ca(2+) elevation after antigen stimulation. Moreover, β-hexosaminidase release induced by antigen was significantly suppressed in MCU-KD cells but not MICU1-KD cells. This suggests that both MCU and MICU1 are involved in mitochondrial Ca(2+) uptake in mast cells, while MCU plays a role in mast cell degranulation.

  7. IgE and mast cells in host defense against parasites and venoms.

    PubMed

    Mukai, Kaori; Tsai, Mindy; Starkl, Philipp; Marichal, Thomas; Galli, Stephen J

    2016-09-01

    IgE-dependent mast cell activation is a major effector mechanism underlying the pathology associated with allergic disorders. The most dramatic of these IgE-associated disorders is the fatal anaphylaxis which can occur in some people who have developed IgE antibodies to otherwise innocuous antigens, such as those contained in certain foods and medicines. Why would such a highly "maladaptive" immune response develop in evolution and be retained to the present day? Host defense against parasites has long been considered the only beneficial function that might be conferred by IgE and mast cells. However, recent studies have provided evidence that, in addition to participating in host resistance to certain parasites, mast cells and IgE are critical components of innate (mast cells) and adaptive (mast cells and IgE) immune responses that can enhance host defense against the toxicity of certain arthropod and animal venoms, including enhancing the survival of mice injected with such venoms. Yet, in some people, developing IgE antibodies to insect or snake venoms puts them at risk for having a potentially fatal anaphylactic reaction upon subsequent exposure to such venoms. Delineating the mechanisms underlying beneficial versus detrimental innate and adaptive immune responses associated with mast cell activation and IgE is likely to enhance our ability to identify potential therapeutic targets in such settings, not only for reducing the pathology associated with allergic disorders but perhaps also for enhancing immune protection against pathogens and animal venoms. PMID:27225312

  8. Arsenic inhibits mast cell degranulation via suppression of early tyrosine phosphorylation events.

    PubMed

    Shim, Juyoung; Kennedy, Rachel H; Weatherly, Lisa M; Hutchinson, Lee M; Pelletier, Jonathan H; Hashmi, Hina N; Blais, Kayla; Velez, Alejandro; Gosse, Julie A

    2016-11-01

    Exposure to arsenic is a global health concern. We previously documented an inhibitory effect of inorganic Arsenite on IgE-mediated degranulation of RBL-2H3 mast cells (Hutchinson et al., 2011; J. Appl. Toxicol. 31: 231-241). Mast cells are tissue-resident cells that are positioned at the host-environment interface, thereby serving vital roles in many physiological processes and disease states, in addition to their well-known roles in allergy and asthma. Upon activation, mast cells secrete several mediators from cytoplasmic granules, in degranulation. The present study is an investigation of Arsenite's molecular target(s) in the degranulation pathway. Here, we report that arsenic does not affect degranulation stimulated by either the Ca(2) (+) ionophore A23187 or thapsigargin, which both bypass early signaling events. Arsenic also does not alter degranulation initiated by another non-IgE-mediated mast cell stimulant, the G-protein activator compound 48/80. However, arsenic inhibits Ca(2) (+) influx into antigen-activated mast cells. These results indicate that the target of arsenic in the degranulation pathway is upstream of the Ca(2) (+) influx. Phospho-Syk and phospho-p85 phosphoinositide 3-kinase enzyme-linked immunosorbent assays data show that arsenic inhibits early phosphorylation events. Taken together, this evidence indicates that the mechanism underlying arsenic inhibition of mast cell degranulation occurs at the early tyrosine phosphorylation steps in the degranulation pathway. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27018130

  9. Mast cell maturation is driven via a group III phospholipase A2-prostaglandin D2–DP1 receptor paracrine axis

    PubMed Central

    Taketomi, Yoshitaka; Ueno, Noriko; Kojima, Takumi; Sato, Hiroyasu; Murase, Remi; Yamamoto, Kei; Tanaka, Satoshi; Sakanaka, Mariko; Nakamura, Masanori; Nishito, Yasumasa; Kawana, Momoko; Kambe, Naotomo; Ikeda, Kazutaka; Taguchi, Ryo; Nakamizo, Satoshi; Kabashima, Kenji; Gelb, Michael H.; Arita, Makoto; Yokomizo, Takehiko; Nakamura, Motonao; Watanabe, Kikuko; Hirai, Hiroyuki; Nakamura, Masataka; Okayama, Yoshimichi; Ra, Chisei; Aritake, Kosuke; Urade, Yoshihiro; Morimoto, Kazushi; Sugimoto, Yukihiko; Shimizu, Takao; Narumiya, Shuh; Hara, Shuntaro; Murakami, Makoto

    2014-01-01

    Microenvironment-based alterations in phenotypes of mast cells influence the susceptibility to anaphylaxis, yet the mechanisms underlying proper maturation of mast cells toward an anaphylaxis-sensitive phenotype are incompletely understood. Here we report that PLA2G3, a mammalian homolog of anaphylactic bee venom phospholipase A2, regulates this process. PLA2G3 secreted from mast cells is coupled with fibroblastic lipocalin-type PGD2 synthase (L-PGDS) to provide PGD2, which facilitates mast-cell maturation via PGD2 receptor DP1. Mice lacking PLA2G3, L-PGDS or DP1, mast cell–deficient mice reconstituted with PLA2G3-null or DP1-null mast cells, or mast cells cultured with L-PGDS–ablated fibroblasts exhibited impaired maturation and anaphylaxis of mast cells. Thus, we describe a lipid-driven PLA2G3–L-PGDS–DP1 loop that drives mast cell maturation. PMID:23624557

  10. Mast cells in human keloid, small intestine, and lung by an immunoperoxidase technique using a murine monoclonal antibody against tryptase.

    PubMed Central

    Craig, S. S.; DeBlois, G.; Schwartz, L. B.

    1986-01-01

    A murine monoclonal antibody (G5) against human lung mast cell tryptase was used for selective staining of human mast cells by an indirect immunoperoxidase method. Human tissues (keloid, small bowel, lung) were fixed in either Carnoy's fluid or neutral buffered formalin. In all three tissues the number and location of G5-stained mast cells corresponded closely with metachromatic toluidine blue-stained mast cells, although the immunospecific technique appeared to be more sensitive. In lung the average concentration of G5-positive mast cells after Carnoy's fixation was 15,695/cu mm of subepithelial tissue in bronchi and bronchioles and 26,580/cu mm of alveolar wall, in small bowel was 20,958/cu mm of mucosa and 8576/cu mm of submucosa, and in keloid was 3068/cu mm. Formalin fixation significantly reduced concentrations of G5-positive mast cells in all tissues except keloid. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:3532813

  11. The regulatory effect of SC-236 (4-[5-(4-chlorophenyl)-3-(trifluoromethyl)-1-pyrazol-1-l] benzenesulfonamide) on stem cell factor induced migration of mast cells

    SciTech Connect

    Kim, Su-Jin; Jeong, Hyun-Ja; Park, Rae-Kil; Lee, Kang-Min; Kim, Hyung-Min; Um, Jae-Young; Hong, Seung-Heon . E-mail: jooklim@wonkwang.ac.kr

    2007-04-15

    SC-236 (4-[5-(4-chlorophenyl)-3-(trifluoromethyl)-1-pyrazol-1-]benzenesulfonamide; C{sub 16}H{sub 11}ClF{sub 3}N{sub 3}O{sub 2}S), is a highly selective cyclooxygenase (COX)-2 inhibitor. Recently, there have been reports that SC-236 protects against cartilage damage in addition to reducing inflammation and pain in osteoarthritis. However, the mechanism involved in the inflammatory allergic reaction has not been examined. Mast cells accumulation can be related to inflammatory conditions, including allergic rhinitis, asthma, and rheumatoid arthritis. The aim of the present study is to investigate the effects of SC-236 on stem cell factor (SCF)-induced migration, morphological alteration, and cytokine production of rat peritoneal mast cells (RPMCs). We observed that SCF significantly induced the migration and morphological alteration. The ability of SCF to enhance migration and morphological alteration was abolished by treatment with SC-236. In addition, production of tumor necrosis factor (TNF)-{alpha}, interleukin (IL)-1{beta}, and vascular endothelial growth factor (VEGF) production induced by SCF was significantly inhibited by treatment with SC-236. Previous work has demonstrated that SCF-induced migration and cytokine production of mast cells require p38 MAPK activation. We also showed that SC-236 suppresses the SCF-induced p38 MAPK activation in RPMCs. These data suggest that SC-236 inhibits migration and cytokine production through suppression of p38 MAPK activation. These results provided new insight into the pharmacological actions of SC-236 and its potential therapeutic role in the treatment of inflammatory allergic diseases.

  12. Mast cells as effector cells of innate immunity and regulators of adaptive immunity.

    PubMed

    Cardamone, Chiara; Parente, Roberta; Feo, Giulia De; Triggiani, Massimo

    2016-10-01

    Mast cells are widely distributed in human organs and tissues and they are particularly abundant at major body interfaces with the external environment such as the skin, the lung and the gastrointestinal tract. Moreover, mast cells are located around blood vessels and are highly represented within central and peripheral lymphoid organs. The strategic distribution of mast cells closely reflects the primary role of these cells in providing first-line defense against environmental dangers, in regulating local and systemic inflammatory reactions and in shaping innate and adaptive immune responses. Human mast cells have pleiotropic and multivalent functions that make them highly versatile cells able to rapidly adapt responses to microenvironmental changes. They express a wide variety of surface receptors including immunoglobulin receptors, pathogen-associated molecular pattern receptors and danger signal receptors. The abundance of these receptors makes mast cells unique and effective surveillance cells able to detect promptly aggression by viral, bacterial and parasitic agents. In addition, mast cells express multiple receptors for cytokines and chemokines that confer them the capacity of being recruited and activated at sites of inflammation. Once activated by immunological or nonimmunological stimuli mast cells secrete a wide spectrum of preformed (early) and de novo synthesized (late) mediators. Preformed mediators are stored within granules and are rapidly released in the extracellular environment to provide a fast vascular response that promotes inflammation and local recruitment of other innate immunity cells such as neutrophils, eosinophils, basophils and monocyte/macrophages. Later on, delayed release of multiple cytokines and chemokines from mast cells further induce modulation of cells of adaptive immunity and regulates tissue injury and, eventually, resolution of inflammation. Finally, mast cells express several costimulatory and inhibitory surface molecules

  13. Motor activity as an unbiased variable to assess anaphylaxis in allergic rats

    PubMed Central

    Abril-Gil, Mar; Garcia-Just, Alba; Cambras, Trinitat; Pérez-Cano, Francisco J; Castellote, Cristina; Franch, Àngels

    2015-01-01

    The release of mediators by mast cells triggers allergic symptoms involving various physiological systems and, in the most severe cases, the development of anaphylactic shock compromising mainly the nervous and cardiovascular systems. We aimed to establish variables to objectively study the anaphylactic response (AR) after an oral challenge in an allergy model. Brown Norway rats were immunized by intraperitoneal injection of ovalbumin with alum and toxin from Bordetella pertussis. Specific immunoglobulin (Ig) E antibodies were developed in immunized animals. Forty days after immunization, the rats were orally challenged with the allergen, and motor activity, body temperature and serum mast cell protease concentration were determined. The anaphylaxis induced a reduction in body temperature and a decrease in the number of animal movements, which was inversely correlated with serum mast cell protease release. In summary, motor activity is a reliable tool for assessing AR and also an unbiased method for screening new anti-allergic drugs. PMID:25716015

  14. Motor activity as an unbiased variable to assess anaphylaxis in allergic rats.

    PubMed

    Abril-Gil, Mar; Garcia-Just, Alba; Cambras, Trinitat; Pérez-Cano, Francisco J; Castellote, Cristina; Franch, Àngels; Castell, Margarida

    2015-10-01

    The release of mediators by mast cells triggers allergic symptoms involving various physiological systems and, in the most severe cases, the development of anaphylactic shock compromising mainly the nervous and cardiovascular systems. We aimed to establish variables to objectively study the anaphylactic response (AR) after an oral challenge in an allergy model. Brown Norway rats were immunized by intraperitoneal injection of ovalbumin with alum and toxin from Bordetella pertussis. Specific immunoglobulin (Ig) E antibodies were developed in immunized animals. Forty days after immunization, the rats were orally challenged with the allergen, and motor activity, body temperature and serum mast cell protease concentration were determined. The anaphylaxis induced a reduction in body temperature and a decrease in the number of animal movements, which was inversely correlated with serum mast cell protease release. In summary, motor activity is a reliable tool for assessing AR and also an unbiased method for screening new anti-allergic drugs.

  15. Allogeneic Transplantation of Müller-Derived Retinal Ganglion Cells Improves Retinal Function in a Feline Model of Ganglion Cell Depletion.