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1

HIV-1 Infection and First Line ART Induced Differential Responses in Mitochondria from Blood Lymphocytes and Monocytes: The ANRS EP45 "Aging" Study  

PubMed Central

Background The ANRS EP45 “Aging” study investigates the cellular mechanisms involved in the accelerated aging of HIV-1 infected and treated patients. The data reported focus on mitochondria, organelles known to be involved in cell senescence. Methods 49 HIV-1 infected patients untreated with antiretroviral therapy, together with 49 seronegative age- and sex-matched control subjects and 81 HIV-1 infected and treated patients, were recruited by 3 AIDS centres (Marseille, Montpellier, Nice; France; http://clinicaltrials.gov/, NCT01038999). In more than 88% of treated patients, the viral load was <40 copies/ml and the CD4+ cell count was >500/mm3. ROS (reactive oxygen species) production and ??m (inner membrane potential) were measured by flow cytometry in blood lymphocytes and monocytes (functional parameters). Three mitochondrial network quantitative morphological parameters were computed using confocal microscopy and image analysis. Three PBMC mitochondrial proteins (porin and subunits 2 and 4 of cytochrome C oxidase encoded by mtDNA or nuclear DNA, respectively) were analysed by western blotting. Results Quantitative changes in PBMC mitochondrial proteins were not induced by either HIV-1 infection or ART. Discriminant analysis integrating functional (ROS production and ??m) or morphological (network volume density, fragmentation and branching) parameters revealed HIV-1 infection and ART differential effects according to cell type. First line ART tended to rescue lymphocyte mitochondrial parameters altered by viral infection, but induced slight changes in monocytes. No statistical difference was found between the effects of three ART regimens on mitochondrial parameters. Correlations between functional parameters and viral load confirmed the damaging effects of HIV-1 in lymphocyte mitochondria. Conclusions In patients considered to be clinically stable, mitochondria exhibited functional and morphological modifications in PBMCs resulting from either direct or indirect effects of HIV-1 infection (lymphocytes), or from first line ART (monocytes). Together with other tissue impairments, these changes may contribute to global aging. Trial Registration ClinicalTrials.gov NCT01038999 NCT01038999

Perrin, Sophie; Cremer, Jonathan; Roll, Patrice; Faucher, Olivia; Menard, Amelie; Reynes, Jacques; Dellamonica, Pierre; Naqvi, Alissa; Micallef, Joelle; Jouve, Elisabeth; Tamalet, Catherine; Solas, Caroline; Pissier, Christel; Arnoux, Isabelle; Nicolino-Brunet, Corine; Espinosa, Leon; Levy, Nicolas; Kaspi, Elise; Robaglia-Schlupp, Andree; Poizot-Martin, Isabelle; Cau, Pierre

2012-01-01

2

IFN-?-activated lymphocytes boost nitric oxide production in grass carp monocytes/macrophages.  

PubMed

It is well known that IFN-? is a prime activator of nitric oxide (NO) production by monocytes/macrophages in mammals and fish. In parallel, whether IFN-?-activated lymphocytes are associated with NO production remains unclear. In this study, grass carp monocytes/macrophages and lymphocytes from head kidney were isolated and effects of recombinant grass carp IFN-? (rgcIFN-?) on NO releases by these two cell populations were determined. Results showed that rgcIFN-? time- and dose-dependently increased NO production by monocytes/macrophages but not lymphocytes, which are consistent with the findings in mammals. Interestingly, rgcIFN-? displayed a greater stimulation on NO production in the co-cultures of monocytes/macrophages and lymphocytes when compared with that in the culture of monocytes/macrophages alone. Furthermore, the media harvested from rgcIFN-?-treated lymphocytes were effective in boosting NO release in monocytes/macrophages. These data suggest that secretions from rgcIFN-?-treated lymphocytes may be involved in the NO release by monocytes/macrophages. To address this hypothesis, effect of rgcIFN-? on the gene expression of inflammatory cytokines in grass carp lymphocytes was examined, showing that it consistently stimulated the mRNA expression of grass carp TNF-? and IL-1? but not IFN-?. Furthermore, treatment of rgcIFN-? combined with recombinant grass carp IL-1? (rgcIL-1?) induced a NO production by monocytes/macrophages, which was significantly higher than those induced by either cytokine alone. It provides the evidence that the cytokines secreted by the activated lymphocytes may facilitate the NO production by monocytes/macrophages. Taken together, our findings point out a new mechanism for the involvement of IFN-?-activated lymphocytes in the NO production by monocytes/macrophages in fish. This knowledge not only strengthens the role of IFN-? in immune system but also provides the evidence for the existence of a close relationship between lymphocytes and monocytes/macrophages in fish. PMID:24056277

Yang, Kun; Zhang, Shengnan; Chen, Danyan; Zhang, Anying; Wang, Xinyan; Zhou, Hong

2013-11-01

3

Lipopolysaccharide Inhibits the Production of Lymphocytic Choriomeningitis Virus in a Human Monocytic Cell Line. (Reannouncement with New Availability Information).  

National Technical Information Service (NTIS)

The human monocytic cell line THP-1 was used as a model to study the mechanism of infection in the monocyte macrophage, a natural target of lymphocytic choriomeningitis virus (LCMV) infection in vivo. Both the virulent strain, LCMV. WE, and the avirulent ...

T. Krakauer C. J. Peters

1993-01-01

4

The monocytic population in chronic lymphocytic leukemia shows altered composition and deregulation of genes involved in phagocytosis and inflammation.  

PubMed

Macrophages reside in tissues infiltrated by chronic lymphocytic leukemia B cells and the extent of infiltration is associated with adverse prognostic factors. We studied blood monocyte population by flow cytometry and whole-genome microarrays. A mixed lymphocyte reaction was performed to evaluate proliferation of T cells in contact with monocytes from patients and normal donors. Migration and gene modulation in normal monocytes cultured with CLL cells were also evaluated. The absolute number of monocytes increased in chronic lymphocytic leukemia patients compared to the number in normal controls (792 ± 86 cells/?L versus 485 ± 46 cells/?L, P=0.003). Higher numbers of non-classical CD14(+)CD16(++) and Tie-2-expressing monocytes were also detected in patients. Furthermore, we performed a gene expression analysis of monocytes in chronic lymphocytic leukemia patients, showing up-regulation of RAP1GAP and down-regulation of tubulins and CDC42EP3, which would be expected to result in impairment of phagocytosis. We also detected gene alterations such as down-regulation of PTGR2, a reductase able to inactivate prostaglandin E2, indicating immunosuppressive activity. Accordingly, the proliferation of T cells in contact with monocytes from patients was inhibited compared to that of cells in contact with monocytes from normal controls. Finally, normal monocytes in vitro increased migration and up-regulated CD16, RAP1GAP, IL-10, IL-8, MMP9 and down-regulated PTGR2 in response to leukemic cells or conditioned media. In conclusion, altered composition and deregulation of genes involved in phagocytosis and inflammation were found in blood monocytes obtained from chronic lymphocytic leukemia patients, suggesting that leukemia-mediated "education" of immune elements may also include the establishment of a skewed phenotype in the monocyte/macrophage population. PMID:23349302

Maffei, Rossana; Bulgarelli, Jenny; Fiorcari, Stefania; Bertoncelli, Linda; Martinelli, Silvia; Guarnotta, Carla; Castelli, Ilaria; Deaglio, Silvia; Debbia, Giulia; De Biasi, Sara; Bonacorsi, Goretta; Zucchini, Patrizia; Narni, Franco; Tripodo, Claudio; Luppi, Mario; Cossarizza, Andrea; Marasca, Roberto

2013-07-01

5

The monocytic population in chronic lymphocytic leukemia shows altered composition and deregulation of genes involved in phagocytosis and inflammation  

PubMed Central

Macrophages reside in tissues infiltrated by chronic lymphocytic leukemia B cells and the extent of infiltration is associated with adverse prognostic factors. We studied blood monocyte population by flow cytometry and whole-genome microarrays. A mixed lymphocyte reaction was performed to evaluate proliferation of T cells in contact with monocytes from patients and normal donors. Migration and gene modulation in normal monocytes cultured with CLL cells were also evaluated. The absolute number of monocytes increased in chronic lymphocytic leukemia patients compared to the number in normal controls (792±86 cells/?L versus 485±46 cells/?L, P=0.003). Higher numbers of non-classical CD14+CD16++ and Tie-2-expressing monocytes were also detected in patients. Furthermore, we performed a gene expression analysis of monocytes in chronic lymphocytic leukemia patients, showing up-regulation of RAP1GAP and down-regulation of tubulins and CDC42EP3, which would be expected to result in impairment of phagocytosis. We also detected gene alterations such as down-regulation of PTGR2, a reductase able to inactivate prostaglandin E2, indicating immunosuppressive activity. Accordingly, the proliferation of T cells in contact with monocytes from patients was inhibited compared to that of cells in contact with monocytes from normal controls. Finally, normal monocytes in vitro increased migration and up-regulated CD16, RAP1GAP, IL-10, IL-8, MMP9 and down-regulated PTGR2 in response to leukemic cells or conditioned media. In conclusion, altered composition and deregulation of genes involved in phagocytosis and inflammation were found in blood monocytes obtained from chronic lymphocytic leukemia patients, suggesting that leukemia-mediated “education” of immune elements may also include the establishment of a skewed phenotype in the monocyte/macrophage population.

Maffei, Rossana; Bulgarelli, Jenny; Fiorcari, Stefania; Bertoncelli, Linda; Martinelli, Silvia; Guarnotta, Carla; Castelli, Ilaria; Deaglio, Silvia; Debbia, Giulia; De Biasi, Sara; Bonacorsi, Goretta; Zucchini, Patrizia; Narni, Franco; Tripodo, Claudio; Luppi, Mario; Cossarizza, Andrea; Marasca, Roberto

2013-01-01

6

Proinflammatory profile of in vitro monocytes in the ageing is affected by lymphocytes presence  

PubMed Central

Background Aging is associated with complex and constant remodeling of the immune function, resulting in an increasing susceptibility to infection and others diseases. The infections caused by Gram-negative microorganisms, present in nursing homes and hospitals, constitute one of the most common infections in the elderly, and are mainly combated by innate immune cells. Although the functions of innate immunity seem more preserved during aging than of adaptive immune mechanisms, two systems operate in an integrated way in the body, so that injury in one part of the immune system inevitably affects the other as they are part of a defensive network. The aim of this study was to investigate the in vitro production of proinflammatory (TNF-?, IL-6, IL-1?, CXCL-8 and MCP-1) and anti-inflammatory (TGF-? and IL-10) cytokines by monocytes, stimulated or not (basal) with lipopolysaccharide, from healthy young and elderly subjects. By means of PBMCs, we also studied if cytokine profile is altered in these different patient groups, in the presence of lymphocytes, under the same experimental conditions. Results The monocytes from elderly presented higher basal production of TNF-?, MCP-1 and lower of TGF-? than young monocytes. PBMC showed similar cytokines production, irrespective age or stimulation presence. In the presence of lymphocytes, the spontaneous production of IL-10 was higher and of TGF-? was lower than monocytes, regardless of age. After LPS-stimulation, the presence of lymphocytes resulted in increased IL-6, IL-1?, MCP-1 and IL-10 and decreased CXCL-8 and TGF-? in comparison to pure culture of monocytes from young patients. With age, the same differences were observed, except for CXCL-8 and TGF-? which production was the same between monocytes and PBMC stimulated with LPS. Conclusion These findings reinforce the systemic state of inflamm-aging frequently reported in elderly and considered a factor of susceptibility to numerous diseases. Still, the cytokine production from just monocytes of the elderly showed alterations, while in the lymphocyte presence not, suggesting an immunomodulator role of lymphocytes on monocytes. In addition, the differences between the production patterns by LPS-stimulated PBMC between young and elderly volunteers can be related with an imbalance in response against Gram-negative bacteria in throughout life.

2013-01-01

7

Inhibition of multiplication of Toxoplasma gondii by human monocytes exposed to T-lymphocyte products  

PubMed Central

The multiplication of Toxoplasma gondii was quantitated in human monocytes in vitro by phase-contrast microscopy. Toxoplasma multiplication was identical in monocytes from subjects byt was significantly inhibited in cells from both sources if the monocytes were preincubated with immune lymphocytes and toxoplasma monocytes were preincubated with immune lymphocytes and toxoplasma antigen. Supernates prepared from toxoplasma-immune lymphocytes incubated with toxoplasma antigen were also effective in inducing in monocytes the capacity to inhibit toxoplasma multiplication. Supernative acitivty was evident after lymphocytes and antigen were incubated for as little as 15 min. The instruction of monocytes was also repid and reversible. Monocytes were fully induced to inhibit toxoplasma multiplication after a 2 h exposure to an active supernate, but they lost their inhibitory capacity on culture in vitro for 48 h in the absece of immune cells or their products. The lymphocytes particupating in the monocyte induction were identified as t cells. The in vitro stimulation of monocytes appeared to exhibit some specificity, since no inhibition of toxopreotein derivative and lymphocytes from tuberculin-positive subjects, concanavalin a-stimulated lymphocytes, or their supermates. Supernates which induced monocytes to inhibit toxoplasma multiplication did not influence parasite growth in HeLa cells.

1975-01-01

8

Synthesis of 5-oxo-6,8,11,14-eicosatetraenoic acid by human monocytes and lymphocytes.  

PubMed

We recently demonstrated that the arachidonate metabolite 5(S)-hydroxy-6,8,11,14-eicosatetraenoic acid (5-HETE) is converted by a highly specific dehydrogenase in human neutrophils to 5-oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ETE), which is a potent stimulator of these cells. The objective of this study was to determine whether 5-oxo-ETE is also formed by monocytes and lymphocytes. Human monocytes (74 +/- 2% pure) and lymphocytes (86 +/- 1% pure) were prepared by successive centrifugations of leukocytes over Ficoll-Paque and Percoll. Both cell types converted 5-HETE to a single major product, which was identified as 5-oxo-ETE. The formation of 5-oxo-ETE was stimulated about twofold by phorbol myristate acetate (PMA; 30 nM). Dehydrogenase activity in monocyte fractions did not appear to be due to platelet contamination, since depletion of platelets did not reduce enzyme activity. The dehydrogenase was localized in membrane fractions from monocytes and required NADP+ as a cofactor. It was specific for eicosanoids containing a 5S-hydroxyl group followed by a 6-trans double bond. We also investigated the formation of 5-oxo-ETE from endogenous arachidonic acid by monocytes. 5-Oxo-ETE, 5-HETE, and leukotriene B4 (LTB4) were present in comparable amounts after incubation of these cells with A23187. PMA (EC50 approximately 4 nM) stimulated the formation of 5-oxo-ETE and 5-HETE and, to a lesser extent, LTB4. Although monocytes released considerably less 5-HETE and LTB4 than neutrophils, they released comparable amounts of 5-oxo-ETE. Unlike neutrophils, monocytes did not convert any of these substances to detectable amounts of omega-oxidation products. Although lymphocytes were capable of converting 5-HETE to 5-oxo-ETE, they released little or no 5-lipoxygenase products in response to A23187. We conclude that monocytes have a high capacity to synthesize 5-oxo-ETE and that its formation is stimulated by activation of protein kinase C. PMID:8691070

Zhang, Y; Styhler, A; Powell, W S

1996-06-01

9

Experiment Lymphocytes of Aragatz Mission: Influence of the Space Flight on Human T Lymphocyte and Monocyte Functions.  

National Technical Information Service (NTIS)

During the last French-Soviet Aragatz mission the experiment Lymphocytes aimed at analyzing the effects of a long duration space flight on the capacity of human T lymphocytes and monocytes to be activated. Peripheral blood from five cosmonauts sampled 24 ...

L. Schaffar I. V. Konstantinova S. Manie I. Serov J. P. Breittmayer

1990-01-01

10

Distinct locomotive patterns of granulocytes, monocytes and lymphocytes in a stable concentration gradient of chemokines.  

PubMed

The pattern of leukocyte locomotion can be changed in many pathological situations, but its accurate analysis is difficult because of technological limitation. In the present study, by using a newly developed time-lapse videomicroscopic technique, we have analyzed the locomotive patterns of leukocytes in a stable concentration gradient of chemokines. Granulocytes, monocytes, and lymphocytes were purified from adult human peripheral blood. Locomotive behavior of the leukocytes was analyzed by an optical assay using a microchannel producing a stable concentration gradient of chemokines. Videomicroscopic analysis showed distinct locomotive patterns of granulocytes, monocytes, and lymphocytes. Granulocytes were intrinsically motile, vigorously moving in random direction without any chemokine stimulation. Upon stimulation with CXCL8/IL-8, the speed of migration was increased from 13.3 +/- 2.8 to 19.4 +/- 2.5 microm/min (P = 0.002, n = 100) and they moved toward the chemokine, although many cells still wandered very much. Stimulation with CCL5/RANTES or CXCL12/SDF-1alpha induced similar changes in locomotive pattern. On the other hand, most lymphocytes did not polarize or move spontaneously without chemokine stimulation. Stimulation with CXCL12 induced directional migration in 37% of the lymphocytes at a speed of 9.6 +/- 1.6 microm/min (n = 100). The movement pattern of monocytes was similar to that of granulocytes in that they tend to become polarized and move spontaneously, but they moved at a very slow speed ranging from 3.9 to 4.2 microm/min even with chemokine stimulation. The new optical assay may be useful for many diagnostic as well as basic studies. PMID:18333846

Bae, S Y; Jung, Y J; Woo, S Y; Park, M H; Seoh, J Y; Ryu, K H

2008-04-01

11

Impact of lymphocyte and monocyte recovery on the outcomes of allogeneic hematopoietic SCT with fludarabine and melphalan conditioning.  

PubMed

We have recently shown that lymphocyte and monocyte recovery by day +100 are associated with survival post myeloablative allogeneic hematopoietic transplant for acute leukemia. We hypothesized that lymphocyte and monocyte recovery would have a similar impact on survival in the reduced intensity setting. To test this hypothesis, we analyzed clinical data from 118 consecutive fludarabine/melphalan-conditioned patients by correlating peripheral blood absolute lymphocyte counts and monocyte counts (ALC and AMC, respectively) at days +15, +30, +60 and +100 with the outcomes. Multivariate analysis revealed that day +100 AMC (risk ratio (RR) 0.22, 95% confidence interval (CI) 0.07-0.73, P=0.01) and mild chronic GVHD (RR 0.09, 95% CI 0.005-0.43, P=0.008) were independently associated with survival. To explore whether the patterns of lymphocyte and monocyte recovery had a prognostic value, we performed unsupervised hierarchical clustering on the studied hematopoietic parameters and identified three patient clusters, A-C. Patient clusters A and B both had improved OS compared with cluster C (77.8 months vs not reached vs 22.3 months, respectively, P<0.001). No patient in cluster C had a day +100 AMC >300. Both severe acute GVHD and relapse occurred more frequently in cluster C. Our data suggest that patients with low AMC by day +100 post fludarabine/melphalan-conditioned allogeneic hematopoietic SCT may be at risk for poor outcomes. PMID:23103674

DeCook, L J; Thoma, M; Huneke, T; Johnson, N D; Wiegand, R A; Patnaik, M M; Litzow, M R; Hogan, W J; Porrata, L F; Holtan, S G

2013-05-01

12

Receptor-mediated Modulation of Human Monocyte, Neutrophil, Lymphocyte, and Platelet Function by Phorbol Diesters  

PubMed Central

The tumor promoting phorbol diesters elicit a variety of responses from normal and leukemic blood cells in vitro by apparently interacting with cellular receptors. The biologically active ligand [20-3H] phorbol 12,13-dibutyrate ([3H]PDBu) bound specifically to intact human lymphocytes, monocytes, polymorphonuclear leukocytes (PMN), and platelets, but not to erythrocytes. Binding, which was comparable for all four blood cell types, occurred rapidly at 23° and 37°C, reaching a maximum by 20-30 min usually followed by a 30-40% decrease in cell associated radioactivity over the next 30-60 min. The time course for binding was temperature dependent with equilibrium binding occurring after 120-150 min at 4°C, with no subsequent loss of cell-associated radioactivity at this temperature. Bound [3H]PDBu could be eluted by addition of unlabeled PDBu. Scatchard analysis of data from 4°C binding studies revealed linear plots with high affinity receptors in these cell types with dissociation constants and receptors per cell of 60 nM and 7.8 × 105/cell for lymphocytes, 51 nM and 15.5 × 105/cell for monocytes, 38 nM and 4.0 × 105/cell for PMN, and 19 nM and 2.9 × 104/cell for platelets. Structure-activity studies using unlabeled phorbol-related compounds demonstrated a close correlation between their abilities to inhibit binding of [3H]PDBu to cells and their abilities to induce cellular responses (monocyte and PMN H2O2 secretion, lymphocyte 3HTdR incorporation, and platelet tritiated serotonin release); phorbol and 4-alpha phorbol were inactive while phorbol 12-myristate 13-acetate (PMA), PDBu, mezerein, and phorbol 12,13-diacetate (in decreasing order of potency) inhibited [3H]PDBu binding and elicited the various responses. Thus, these high affinity, specific receptors for the phorbol diesters, present on monocytes, lymphocytes, PMN, and platelets, mediate the pleiotypic effects induced by these ligands.

Goodwin, Bonnie J.; Weinberg, J. Brice

1982-01-01

13

T-lymphocyte induction of human monocyte angiotensin converting enzyme (ACE) is not dependent upon T-lymphocyte proliferation  

SciTech Connect

Human peripheral blood monocytes cultured in serum free media for seven days show a basal activity of the ectoenzyme ACE which is augmented 2-3 times by the presence of autologous peripheral blood T-lymphocytes. Since these two cell types are also involved in autologous mixed lymphocyte reaction if serum is present, the authors compared the ability of T-cells to stimulate ACE activity in the presence or absence of proliferation (measured by /sup 3/H-thymidine incorporation). By the seventh day, cultures with 5% AB/sup +/ serum showed significant increase in proliferation but no increase in ACE activity compared to the serum free cultures. Even higher proliferation rate achieved by co-culturing T-lymphocytes with allogeneic monocytes did not increase ACE production; on the contrary, ACE activity remained at the basal level. Monocyte-T-cell co-cultures stimulated with increasing concentrations of ConA or PHA showed dose dependent increases in proliferation but parallel decreases in ACE activity. Addition of soluble antigen (Candida albicans) also enhanced proliferation but not ACE synthesis. They conclude that T-lymphocyte induction of monocyte ACE is a result of cooperation between autologous cells which is not dependent upon T-cell proliferation.

Vuk-Pavlovic, Z.; Rohrbach, M.S.

1986-03-05

14

B lymphocytes trigger monocyte mobilization and impair heart function after acute myocardial infarction  

PubMed Central

Acute myocardial infarction is a severe ischemic disease responsible for heart failure and sudden death. Here, we show that after acute myocardial infarction in mice, mature B lymphocytes selectively produce Ccl7 and induce Ly6Chi monocyte mobilization and recruitment to the heart, leading to enhanced tissue injury and deterioration of myocardial function. Genetic (Baff receptor deficiency) or antibody-mediated (CD20- or Baff-specific antibody) depletion of mature B lymphocytes impeded Ccl7 production and monocyte mobilization, limited myocardial injury and improved heart function. These effects were recapitulated in mice with B cell–selective Ccl7 deficiency. We also show that high circulating concentrations of CCL7 and BAFF in patients with acute myocardial infarction predict increased risk of death or recurrent myocardial infarction. This work identifies a crucial interaction between mature B lymphocytes and monocytes after acute myocardial ischemia and identifies new therapeutic targets for acute myocardial infarction.

Zouggari, Yasmine; Ait-Oufella, Hafid; Bonnin, Philippe; Simon, Tabassome; Sage, Andrew P; Guerin, Coralie; Vilar, Jose; Caligiuri, Giuseppina; Tsiantoulas, Dimitrios; Laurans, Ludivine; Dumeau, Edouard; Kotti, Salma; Bruneval, Patrick; Charo, Israel F; Binder, Christoph J; Danchin, Nicolas; Tedgui, Alain; Tedder, Thomas F; Silvestre, Jean-Sebastien; Mallat, Ziad

2014-01-01

15

Lymphocyte, monocyte, and granulocyte proteins compared by use of two-dimensional electrophoresis  

SciTech Connect

Cellular proteins were compared from normal human blood lymphocytes, monocytes, and granulocytes, using high-resolution two-dimensional electrophoresis. The leukocytes were isolated from peripheral blood by centrifugation on density step gradients (yielding a fraction of purified granulocytes and a lymphocyte/monocyte mixture) and monocytes were subsequently separated from lymphocytes by virtue of their adherence to plastic. The cells were labeled with (/sup 35/S)-methionine after various intervals in culture, then solubilized and analyzed by two-dimensional electrophoresis. Although most proteins in each cell type are common to all three, there are nevertheless several specific marker proteins that distinguish one cell type from another. We also examined the appearance of these markers in three lines of cultured cells from humans (GM607, a B-lymphoblastoid line; HL-60, a promyelocytic leukemic line; and 1494, a normal skin fibroblast).

Gemmell, M.A.; Anderson, N.L.

1982-04-01

16

Immature Dendritic Cells Generated from Cryopreserved Human Monocytes Show Impaired Ability to Respond to LPS and to Induce Allogeneic Lymphocyte Proliferation  

PubMed Central

Dendritic cells play a key role in the immune system, in the sensing of foreign antigens and triggering of an adaptive immune response. Cryopreservation of human monocytes was investigated to understand its effect on differentiation into immature monocyte-derived dendritic cells (imdDCs), the response to inflammatory stimuli and the ability to induce allogeneic lymphocyte proliferation. Cryopreserved (crp)-monocytes were able to differentiate into imdDCs, albeit to a lesser extent than freshly (frh)-obtained monocytes. Furthermore, crp-imdDCs had lower rates of maturation and cytokine/chemokine secretion in response to LPS than frh-imdDCs. Lower expression of Toll-like receptor 4 (at 24 and 48 h) and higher susceptibility to apoptosis in crp-imdDCs than in fresh cells would account for the impaired maturation and cytokine/chemokine secretion observed. A mixed leukocyte reaction showed that lymphocyte proliferation was lower with crp-imdDCs than with frh-imdDCs. These findings suggested that the source of monocytes used to generate human imdDCs could influence the accuracy of results observed in studies of the immune response to pathogens, lymphocyte activation, vaccination and antigen sensing. It is not always possible to work with freshly isolated monocytes but the possible effects of freezing/thawing on the biology and responsiveness of imdDCs should be taken into account.

Silveira, Guilherme Ferreira; Wowk, Pryscilla Fanini; Machado, Analia Maria Breckenfeld; dos Santos, Claudia Nunes Duarte; Bordignon, Juliano

2013-01-01

17

Prognostic impact of circulating monocytes and lymphocyte-to-monocyte ratio on previously untreated metastatic non-small cell lung cancer patients receiving platinum-based doublet.  

PubMed

The link between circulating lymphocyte-to-monocyte ratio (LMR) and newly diagnosed metastatic non-small cell lung cancer (NSCLC) is not fully defined. The study was conducted to evaluate the prognostic impact of LMR on survival outcomes in previously untreated metastatic NSCLC patients receiving platinum-based doublet. Chemotherapy-naive metastatic NSCLC patients undergoing platinum-based doublet were retrospectively enrolled. Clinical features regarding gender, age, Eastern Cooperative Oncology Group (ECOG) performance status, histology, absolute lymphocyte count (ALC), absolute monocyte count (AMC) and LMR were collected to determinate their prognostic impact on progression-free survival (PFS) and overall survival (OS). Up to 370 patients were eligible for the study. By univariate analysis, ECOG performance status, histology, ALC, AMC and LMR were showed to be significantly associated with PFS and OS. In subsequent Cox multivariate analysis, non-squamous cell carcinoma, ALC ? 2.45 × 10(9)/L, AMC <0.45 × 10(9)/L and LMR ? 4.56 were demonstrated to be independently correlated with better PFS. In addition, independent favorable prognostic factors for OS were only limited to LMR ? 4.56 and non-squamous cell carcinoma, whereas ECOG performance status of 2 and AMC ? 0.45 × 10(9)/L remained as independently inferior prognostic indicators for OS. Our findings implicate that circulating AMC and LMR are regarded as independent prognostic factors for PFS and OS in previously untreated metastatic NSCLC patients receiving platinum-based doublet. PMID:24927957

Lin, Gui-Nan; Peng, Jie-Wen; Xiao, Jian-jun; Liu, Dong-Ying; Xia, Zhong-Jun

2014-07-01

18

HIV infection of monocytes inhibits the T-lymphocyte proliferative response to recall antigens, via production of eicosanoids.  

PubMed Central

Human monocytes infected in vitro with human immunodeficiency virus (HIV) soon after adherence to plastic substrate demonstrated a significantly decreased ability to restimulate autologous immune T-lymphocyte proliferation after exposure to soluble (tetanus toxoid) and particulate [herpes simplex virus (HSV)] antigen. Incubation with the cyclo-oxygenase inhibitor, indomethacin (2-5 microM), prevented inhibition of antigen-stimulated lymphocyte proliferation. The inhibitory activity was identified in ultrafiltrates containing the low molecular weight fraction (less than 3000 MW) of supernatants from HIV-infected monocyte cultures. This activity was significantly and markedly reduced in similar ultrafiltrates prepared from indomethacin-treated cultures. Increased concentrations of prostaglandin E2 (PGE2) were detected in ultrafiltrates from HIV-infected monocyte cultures compared with uninfected cultures and cultures preincubated with indomethacin. Ultrafiltrates were inhibitory when added during the presentation of antigen to T lymphocytes but not when removed from monocyte cultures prior to the addition of lymphocytes. In addition, ultrafiltrates inhibited antigen-stimulated lymphocyte proliferation and PHA-induced lymphocyte proliferation to the same extent. These data indicate that cyclo-oxygenase products of arachidonic acid, including PGE2, are produced in excess by HIV-infected monocytes and that PGE2 and perhaps other cyclo-oxygenase products are implicated in the inhibition of antigen-stimulated lymphocyte proliferation via a direct effect on T lymphocytes.

Foley, P; Kazazi, F; Biti, R; Sorrell, T C; Cunningham, A L

1992-01-01

19

Plasma exosomes can deliver exogenous short interfering RNA to monocytes and lymphocytes  

PubMed Central

Despite the promise of RNA interference (RNAi) and its potential, e.g. for use in cancer therapy, several technical obstacles must first be overcome. The major hurdle of RNAi-based therapeutics is to deliver nucleic acids across the cell’s plasma membrane. This study demonstrates that exosome vesicles derived from humans can deliver short interfering RNA (siRNA) to human mononuclear blood cells. Exosomes are nano-sized vesicles of endocytic origin that are involved in cell-to-cell communication, i.e. antigen presentation, tolerance development and shuttle RNA (mainly mRNA and microRNA). Having tested different strategies, an optimized method (electroporation) was used to introduce siRNA into human exosomes of various origins. Plasma exosomes (exosomes from peripheral blood) were used as gene delivery vector (GDV) to transport exogenous siRNA to human blood cells. The vesicles effectively delivered the administered siRNA into monocytes and lymphocytes, causing selective gene silencing of mitogen-activated protein kinase 1. These data suggest that human exosomes can be used as a GDV to provide cells with heterologous nucleic acids such as therapeutic siRNAs.

Wahlgren, Jessica; Karlson, Tanya De L.; Brisslert, Mikael; Vaziri Sani, Forugh; Telemo, Esbjorn; Sunnerhagen, Per; Valadi, Hadi

2012-01-01

20

Methods for defining distinct bioenergetic profiles in platelets, lymphocytes, monocytes, and neutrophils, and the oxidative burst from human blood  

PubMed Central

Peripheral blood mononuclear cells and platelets have long been recognized as having the potential to act as sensitive markers for mitochondrial dysfunction in a broad range of pathological conditions. However, the bioenergetic function of these cells has not been examined from the same donors, yet this is important for the selection of cell types for translational studies. Here, we demonstrate the measurement of cellular bioenergetics in isolated human monocytes, lymphocytes, and platelets, including the oxidative burst from neutrophils and monocytes from individual donors. With the exception of neutrophils, all cell types tested exhibited oxygen consumption that could be ascribed to oxidative phosphorylation with each having a distinct bioenergetic profile and distribution of respiratory chain proteins. In marked contrast, neutrophils were essentially unresponsive to mitochondrial respiratory inhibitors indicating that they have a minimal requirement for oxidative phosphorylation. In monocytes and neutrophils, we demonstrate the stimulation of the oxidative burst using phorbol 12-myristate 13-acetate and its validation in normal human subjects. Taken together, these data suggest that selection of cell type from blood cells is critical for assessing bioenergetic dysfunction and redox biology in translational research.

Chacko, Balu K; Kramer, Philip A; Ravi, Saranya; Johnson, Michelle S; Hardy, Robert W; Ballinger, Scott W; Darley-Usmar, Victor M

2013-01-01

21

Absolute monocyte count trichotomizes chronic lymphocytic leukemia into high risk patients with immune dysregulation, disease progression and poor survival.  

PubMed

Peripheral absolute monocyte count (AMC) has been reported to correlate with clinical outcome in different types of cancers. This association may relate to alteration in circulating monocytic subpopulations and tumor infiltrating macrophages. In this study we evaluated the clinical significance of peripheral AMC in 80 treatment naive patients with CLL. Measurement of AMC was based on direct morphological enumeration, due to our findings that complete blood count data may yield incorrect monocytes enumeration values in CLL. The median AMC in patients with CLL was within normal limits, however the AMC range exceeded the values of healthy individuals. The AMC trichotomized patients into 3 distinct sub-groups with different characteristics and outcomes. High AMC patients were younger and had higher absolute lymphocytes count, while patients with low AMC had prominent immune dysregulation (lower serum IgA levels, susceptibility to infections and a tendency for positive direct anti-globulin test). The low and high AMC patients had a shorter time to treatment compared to the intermediates AMC subgroups, whereas low AMC was associated with increased mortality caused by infectious complications. In conclusion, AMC quantification during the disease course classifies CLL patients into subgroups with unique clinical features and outcomes. PMID:23937985

Herishanu, Yair; Kay, Sigi; Sarid, Nadav; Kohan, Pedram; Braunstein, Rony; Rotman, Rachel; Deutsch, Varda; Ben-Ezra, Jonathan; Naparstek, Elizabeth; Perry, Chava; Katz, Ben-Zion

2013-10-01

22

HIV1 Infection and First Line ART Induced Differential Responses in Mitochondria from Blood Lymphocytes and Monocytes: The ANRS EP45 “Aging” Study  

Microsoft Academic Search

BackgroundThe ANRS EP45 “Aging” study investigates the cellular mechanisms involved in the accelerated aging of HIV-1 infected and treated patients. The data reported focus on mitochondria, organelles known to be involved in cell senescence.Methods49 HIV-1 infected patients untreated with antiretroviral therapy, together with 49 seronegative age- and sex-matched control subjects and 81 HIV-1 infected and treated patients, were recruited by

Sophie Perrin; Jonathan Cremer; Patrice Roll; Olivia Faucher; Amélie Ménard; Jacques Reynes; Pierre Dellamonica; Alissa Naqvi; Joëlle Micallef; Elisabeth Jouve; Catherine Tamalet; Caroline Solas; Christel Pissier; Isabelle Arnoux; Corine Nicolino-Brunet; Léon Espinosa; Nicolas Lévy; Elise Kaspi; Andrée Robaglia-Schlupp; Isabelle Poizot-Martin; Pierre Cau

2012-01-01

23

Comparative Analysis of Total and Integrated HIV1 DNA in Peripheral CD4 Lymphocytes and Monocytes After Long Treatment with HAART  

Microsoft Academic Search

Objective: To determine the level of total and integrated HIV-1 DNA load in CD4 lymphocytes and monocytes of patients undergoing HAART treatment for at least 2 years.Methods: CD4 lymphocytes were isolated by subjecting monocyte-depleted blood samples to immune-purging carried out with M-450 Dynabeads. Monocytes were separated by blood through a combined procedure of cell adherence to dishes and complement induced

S. Calcaterra; G. Cappiello; A. Di Caro; A. R. Garbuglia; A. Benedetto

2001-01-01

24

Inhibitory and stimulatory effects of Pseudomonas aeruginosa pyocyanine on human T and B lymphocytes and human monocytes.  

PubMed Central

Pyocyanine, a pigment produced by Pseudomonas aeruginosa, has dual dose-dependent stimulatory as well as inhibitory effects on immune responses in vitro as measured by DNA synthesis of human T and B lymphocytes, interleukin-2 (IL-2) production by human T lymphocytes, immunoglobulin production by human B lymphocytes, and monokine production by human monocytes. In general, stimulatory activity was found at low concentrations of pyocyanine, whereas high concentrations of the pigment resulted in an inhibition of responses. At a pyocyanine concentration of 0.1 micrograms/ml or less the proliferation of T and B lymphocytes was enhanced, but at 0.5 micrograms/ml it was suppressed. IL-2 production by T lymphocytes was enhanced at concentrations up to 0.5 micrograms/ml but totally inhibited at 1.0 micrograms/ml. The differentiation of B lymphocytes to become immunoglobulin-producing cells was also enhanced in the presence of low doses of pyocyanine, whereas secretion of immunoglobulin by B lymphocytes was suppressed at all concentrations of pyocyanine. In contrast to the dual effects of pyocyanine on lymphocyte response, lipopolysaccharide-induced IL-1 and tumor necrosis factor release by monocytes was markedly enhanced by low as well as high concentrations of pyocyanine. From these results we conclude that this property of pyocyanine may lead to suppression of specific defense mechanisms and enhance harmful inflammatory reactions of the host during infection with Pseudomonas aeruginosa.

Ulmer, A J; Pryjma, J; Tarnok, Z; Ernst, M; Flad, H D

1990-01-01

25

Malignancy-associated changes in monocytes and lymphocytes in acute leukemias measured by high-resolution image processing.  

PubMed

A number of methods are available for classifying lymphoid and myeloid leukemias in peripheral blood and bone marrow. However, in clinical diagnosis an initial and particularly important step is morphologic analysis. All the cells in this investigation were classified by two hematologic experts. In most cases, immunophenotyping and immunocytochemical analyses were performed. Routinely prepared Romanowsky-Giemsa-stained peripheral blood smears (approximately 23,000 cells) were scanned by a high-resolution color TV/microscope system and analyzed by color and texture algorithms. In addition to blast cells, lymphocytes and monocytes exhibited a leukemia-associated change in morphology. The calculated texture and color features were most significant for the subtyping performed by the statistical program. With multivariate statistical analysis, seven mathematical subtypes of lymphocytes and five of monocytes could be found over all the specimens. Acute myeloblastic leukemia (AML, M1-M2), acute myelomonocytic leukemia (AMMOL, M4) and acute monocytic leukemia (AMOL, M5) could be differentiated by their distributions of monocyte subtypes. However, this was impossible for the lymphocyte subtypes. Acute lymphoblastic leukemias (B-ALL and T-ALL) were discernible with the aid of lymphocyte subtypes and acute myeloid conditions from viral infections, such as with the Epstein-Barr virus. The method increased the relevance of image processing in clinical diagnosis of acute leukemias and showed that the "normal" cell populations were not really normal in malignant leukemias. PMID:8297427

Harms, H; Gunzer, U; Baumann, I; Serbouti, S

1993-12-01

26

Type 1 Diabetes Therapy Beyond T Cell Targeting: Monocytes, B Cells, and Innate Lymphocytes  

PubMed Central

Recent clinical trials, investigating type 1 diabetes (T1D), have focused mainly on newly diagnosed individuals who have developed diabetes. We need to continue our efforts to understand disease processes and to rationally design interventions that will be safe and specific for disease, but at the same time not induce undesirable immunosuppression. T cells are clearly involved in the pathogenesis of T1D, and have been a major focus for both antigen-specific and non-antigen-specific therapy, but thus far no single strategy has emerged as superior. As T1D is a multifactorial disease, in which multiple cell types are involved, some of these pathogenic and regulatory cell pathways may be important to consider. In this review, we examine evidence for whether monocytes, B cells, and innate lymphocytes, including natural killer cells, may be suitable targets for intervention.

Wong, F. Susan; Wen, Li

2012-01-01

27

Interferon-lambda (IFN-?) induces signal transduction and gene expression in human hepatocytes, but not in lymphocytes or monocytes  

PubMed Central

This study compared the ability of IFN-? and IFN-? to induce signal transduction and gene expression in primary human hepatocytes, PBLs, and monocytes. IFN-? drug products are widely used to treat chronic HCV infection; however, IFN-? therapy often induces hematologic toxicities as a result of the broad expression of IFNARs on many cell types, including most leukocytes. rIFN-?1 is currently being tested as a potential alternative to IFN-? for treating chronic HCV. Although IFN-? has been shown to be active on hepatoma cell lines, such as HepG2 and Huh-7, its ability to induce responses in primary human hepatocytes or leukocytes has not been examined. We found that IFN-? induces activation of Jak/STAT signaling in mouse and human hepatocytes, and the ability of IFN-? to induce STAT activation correlates with induction of numerous ISGs. Although the magnitude of ISG expression induced by IFN-? in hepatocytes was generally lower than that induced by IFN-?, the repertoire of regulated genes was quite similar. Our findings demonstrate that although IFN-? and IFN-? signal through distinct receptors, they induce expression of a common set of ISGs in hepatocytes. However, unlike IFN-?, IFN-? did not induce STAT activation or ISG expression by purified lymphocytes or monocytes. This important functional difference may provide a clinical advantage for IFN-? as a treatment for chronic HCV infection, as it is less likely to induce the leukopenias that are often associated with IFN-? therapy.

Dickensheets, Harold; Sheikh, Faruk; Park, Ogyi; Gao, Bin; Donnelly, Raymond P.

2013-01-01

28

CXCR4 and CCR5 ligands cooperate in monocyte and lymphocyte migration and in inhibition of dual-tropic (R5/X4) HIV-1 infection.  

PubMed

One of the most important functions of chemokines and their receptors is the regulation of directional migration of leukocytes within tissues. In specific tissue compartments, cells are exposed to multiple chemokines presented in complex dimensional and temporal patterns. Therefore, a leukocyte requires the mechanisms to integrate the various directional signals it receives from different chemoattractants. In this study, we report that CCL3, CCL5, and CCL8, three potent mononuclear cell chemoattractants, are able to synergize with the homeostatic chemokine CXCL12 in the migration of CD14(+) monocytes, CD3(+) T-lymphocytes, or PHA-activated lymphoblasts. In addition, CCL5 augmented the CXCR4 ligand-driven ERK phosphorylation in mononuclear cells. Furthermore, the synergistic effect between CCL5 and CXCL12 in monocyte chemotaxis is inhibited in the presence of specific CCR1 antibody and AMD3100, but not by maraviroc. In HIV-1 infection assays, a combination of CXCL12 and CCL5 cooperated to inhibit the replication of the dual-tropic (R5/X4) HIV-1 HE strain. Finally, although the dual-tropic HIV-1 strain was barely suppressed by AMD3100 or maraviroc alone, HIV-1 infection was completely blocked by the combination of these two receptor antagonists. Our data demonstrate the cooperation between CCL5 and CXCL12, which has implications in migration of monocytes/lymphocytes during inflammation and in HIV-1 infection. PMID:21381021

Gouwy, Mieke; Struyf, Sofie; Berghmans, Nele; Vanormelingen, Christophe; Schols, Dominique; Van Damme, Jo

2011-04-01

29

Inflammatory monocytes activate memory CD8+ T and innate NK lymphocytes independent of cognate antigen during microbial pathogen invasion  

PubMed Central

SUMMARY Memory CD8+ T cells induced upon immunization exhibit improved functional features that contribute to protection of immunized hosts. Although both cognate antigen recognition and inflammation are important for memory CD8+ T cell reactivation, the relative contribution of these factors and the cell types providing these signals in vivo are poorly defined. Here, we show that Ly6C+CCR2+ inflammatory monocytes, a subset of monocytes, largely orchestrate memory CD8+ T and NK lymphocytes activation by differentiating into interleukin-18 (IL-18)- and IL-15-producing cells in an inflammasome and type I interferon-IRF3-dependent manner. Memory CD8+ T cells became potent effector cells by sensing inflammation from monocytes independently of their cognate antigen. Like NK cells, they underwent rapid mobilization, upregulated intense and sustained effector functions during bacterial, viral and parasitic infections, and contributed to innate responses and protection in vivo. Thus, inflammatory monocyte-derived IL-18 and IL-15 are critical to initiate memory CD8+ T and NK lymphocytes differentiation into antimicrobial effector cells.

Soudja, Saidi M'Homa; Ruiz, Anne L.; Marie, Julien C.; Lauvau, Gregoire

2012-01-01

30

P2 receptor mRNA expression profiles in human lymphocytes, monocytes and CD34+ stem and progenitor cells  

Microsoft Academic Search

BACKGROUND: Extracellular nucleotides (ATP, ADP, UTP and UDP) exert a wide range of biological effects in blood cells mediated by multiple ionotropic P2X receptors and G protein-coupled P2Y receptors. Although pharmacological experiments have suggested the presence of several P2 receptor subtypes on monocytes and lymphocytes, some results are contradictory. Few physiological functions have been firmly established to a specific receptor

Lingwei Wang; Sten Eirik W Jacobsen; Anders Bengtsson; David Erlinge

2004-01-01

31

Effect of acute and regular exercise on growth hormone secretagogue receptor-1a expression in human lymphocytes, T cell subpopulation and monocytes.  

PubMed

The orexigenic peptide hormone ghrelin exerts potent inhibitory effects on pro-inflammatory cytokine release via the growth hormone secretagogue receptor-1a (GHS-R1a) on T cells and monocytes. As such, ghrelin is a promising therapeutic agent for the treatment of inflammatory conditions, but these effects depend on the availability of GHS-R1a. The aim of this study was to determine the effect of acute exercise on GHS-R1a expression on circulating CD14+ monocytes, total lymphocytes and CD3+ T cells. Nine male club-standard cyclists cycled for 1h at 75% V?O2peak (EX) or rested (REST) in a randomised cross-over design. Compared with the equivalent times in REST, the concentration of circulating GHS-R1a+ lymphocytes and monocytes was higher in EX at immediately and 1 and 2h post-exercise (all p<.05). The concentration of CD3+GHS-R1a+ cells was higher in EX than in REST immediately post-exercise only (258 (203)cells?l(-1) vs. 62 (42)cells?l(-1), p<.05). Density of GHS-R1a receptor expression was unaffected by trial or time. Comparison of active participants at rest with 7 age-, sex- and BMI-matched sedentary controls revealed a higher concentration of GHS-R1a+ lymphocytes in active males (p<.05). These findings suggest a preferential recruitment of specific cell subpopulations expressing GHS-R1a into the peripheral circulation with acute and regular exercise. Given that the anti-inflammatory effects of ghrelin depend on the availability of GHS-R1a, the preferential recruitment of subpopulations with high anti-inflammatory potential found here add a novel aspect to the potential mechanisms by which exercise acts to reduce pro-inflammatory cytokine levels. PMID:24095896

Bishop, Nicolette C; Hayashida, Harumi; Clark, Megan; Coombs, Charlotte; Miller, Sean; Stensel, David J

2014-07-01

32

Leukoreduction system chambers are an efficient, valid, and economic source of functional monocyte-derived dendritic cells and lymphocytes.  

PubMed

The demand for human monocyte-derived dendritic cells (moDCs), as well as for primary human B and T lymphocytes for immunological research purposes has been increased in recent years. Classically, these monocytes are isolated from blood, leukapheresis products or buffy coats of healthy donors by plastic adherence of peripheral blood mononuclear cells (PBMCs), followed by stimulation with granulocyte macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-4, while lymphocytes are usually isolated from the non-adherent fraction (NAF) by magnetic cell sorting. However, donor-blood is a limited resource and not every blood bank offers leukapheresis products or buffy coats for laboratory use. Additionally, a leukapheresis is very expensive and also the generation/isolation of cells is time- and cost-intensive. To overcome some of these obstacles, we evaluated if low-cost leukoreduction system chambers (LRSCs), which arise after routine donor plateletpheresis procedures, and are usually discarded, would be an alternative and appropriate source of PBMCs to generate moDCs and to isolate lymphocytes. By analyzing the number and phenotype of immature and mature dendritic cells (DCs), as well as of B and T lymphocytes derived from LRSCs, we found all cells to be of high quantity and quality. Further investigations on DCs comprising transwell migration assays, allogeneic mixed lymphocyte reactions (MLR), cytokine secretion assays, and cytotoxic T cell induction assays revealed high migratory, as well as stimulatory capacity of these cells. In addition, DCs and T cells were efficiently electroporated with mRNA and showed characteristic cytokine production after co-culture, demonstrating LRSCs as an efficient, valid, and economic source for generation of moDCs and lymphocytes for research purposes. PMID:23932569

Pfeiffer, Isabell A; Zinser, Elisabeth; Strasser, Erwin; Stein, Marcello F; Dörrie, Jan; Schaft, Niels; Steinkasserer, Alexander; Knippertz, Ilka

2013-11-01

33

Cannabidiol induced a contrasting pro-apoptotic effect between freshly isolated and precultured human monocytes  

Microsoft Academic Search

It has been documented that cannabidiol (CBD) induced apoptosis in a variety of transformed cells, including lymphocytic and monocytic leukemias. In contrast, a differential sensitivity between normal lymphocytes and monocytes to CBD-mediated apoptosis has been reported. The present study investigated the pro-apoptotic effect of CBD on human peripheral monocytes that were either freshly isolated or precultured for 72 h. CBD

Hsin-Ying Wu; An-Chi Chang; Chia-Chi Wang; Fu-Hua Kuo; Chi-Ya Lee; Der-Zen Liu; Tong-Rong Jan

2010-01-01

34

CXCL12-Induced Monocyte-Endothelial Interactions Promote Lymphocyte Transmigration Across an in Vitro Blood-Brain Barrier  

PubMed Central

The accumulation of inflammatory cells in the brain parenchyma is a critical step in the pathogenesis of neuroinflammatory diseases such as multiple sclerosis (MS). Chemokines and adhesion molecules orchestrate leukocyte transmigration across the blood-brain barrier (BBB), but the dynamics of chemokine receptor expression during leukocyte transmigration are unclear. We describe an in vitro BBB model system using human brain microvascular endothelial cells that incorporates shear forces mimicking blood flow to elucidate how chemokine receptor expression is modulated during leukocyte transmigration. In the presence of the chemokine CXCL12, we examined modulation of its receptor CXCR4 on human T cells, B cells, and monocytes transmigrating across the BBB under flow conditions. CXCL12 stimulated transmigration of CD4+ and CD8+ T cells, CD19+ B cells, and CD14+ monocytes. Transmigration was blocked by CXCR4-neutralizing antibodies. Unexpectedly, CXCL12 selectively down-regulated CXCR4 on transmigrating monocytes, but not T cells. Monocytes underwent preferential CXCL12-mediated adhesion to the BBB in vitro compared with lymphocytes. These findings provide new insights into leukocyte-endothelial interactions at the BBB under conditions mimicking blood flow and suggest that in vitro BBB models may be useful for identifying chemokine receptors that could be modulated therapeutically to reduce neuroinflammation in diseases such as MS.

Man, Shumei; Tucky, Barbara; Cotleur, Anne; Drazba, Judith; Takeshita, Yukio; Ransohoff, Richard M.

2013-01-01

35

Prostaglandin E2 inhibits advanced glycation end product-induced adhesion molecule expression on monocytes, cytokine production, and lymphocyte proliferation during human mixed lymphocyte reaction.  

PubMed

Posttransplant diabetes mellitus is a frequent complication among transplant recipients. Ligation of advanced glycation end products (AGEs) with their receptor on monocytes/macrophages plays a role in diabetes complications. The enhancement of adhesion molecule expression on monocytes/macrophages activates T cells, reducing allograft survival. In previous work, we found that toxic AGEs, AGE-2 and AGE-3, induced the expression of intracellular adhesion molecule-1, B7.1, B7.2, and CD40 on monocytes, production of interferon-gamma and tumor necrosis factor alpha, and lymphocyte proliferation during human mixed lymphocyte reaction. AGE-induced up-regulation of adhesion molecule expression was involved in cytokine production and lymphocyte proliferation. Prostaglandin E2 (PGE2) concentration-dependently inhibited the actions of AGE-2 and AGE-3. The effects of PGE2 were mimicked by an EP2 receptor agonist, ONO-AE1-259-01 (11,15-O-dimethyl PGE2), and an EP4 receptor agonist, ONO-AE1-329 [16-(3-methoxymethyl)phenyl-omega-tetranor-3,7dithia PGE1]. An EP2 receptor antagonist, AH6809 (6-isopropoxy-9-oxaxanthene-2-carboxylic acid), and an EP4 receptor antagonist, AH23848 [(4Z)-7-[(rel-1S,2S,5R)-5-((1,1'-biphenyl-4-yl)methoxy)-2-(4-morpholinyl)-3-oxocyclopentyl]-4-heptenoic acid], inhibited the actions of PGE2. The stimulation of EP2 and EP4 receptors is reported to increase cAMP levels. The effects of PGE2 were reversed by protein kinase A (PKA) inhibitors and mimicked by dibutyryl cAMP and an adenylate cyclase activator, forskolin. These results as a whole indicate that PGE2 inhibited the actions of AGE-2 and AGE-3 via EP2/EP4 receptors and the cAMP/PKA pathway. PMID:20558773

Takahashi, Hideo Kohka; Zhang, Jiyong; Mori, Shuji; Liu, Keyue; Wake, Hidenori; Liu, Rui; Sadamori, Hiroshi; Matsuda, Hiroaki; Yagi, Takahito; Yoshino, Tadashi; Nishibori, Masahiro

2010-09-01

36

The lymphocyte/monocyte ratio predicts poor clinical outcome and improves the predictive accuracy in patients with soft tissue sarcomas.  

PubMed

Increasing evidence indicates the involvement of inflammation and coagulation in cancer progression and metastases. Inflammatory biomarkers hold great promise for improving the predictive ability of existing prognostic tools in cancer patients. In the present study, we investigated several inflammatory indices with regard to their prognostic relevance for predicting clinical outcome in soft tissue sarcoma (STS) patients. Three hundred and forty STS patients were divided into a training set (n?=?170) and a validation set (n?=?170). Besides well-established clinico-pathological prognostic factors, we evaluated the prognostic value of the neutrophil/lymphocyte (N/L) ratio, the lymphocyte/monocyte (L/M) ratio and the platelet/lymphocyte (P/L) ratio using Kaplan-Meier curves and univariate as well as multivariate Cox regression models. Additionally, we developed a nomogram by supplementing the L/M ratio to the well-established Kattan nomogram and evaluated the predictive accuracy of this novel nomogram by applying calibration and Harrell's concordance index (c-index). In multivariate analysis, a low L/M ratio was significantly associated with decreased CSS and DFS (HR?=?0.41, 95% CI?=?0.18-0.97, p?=?0.043; HR?=?0.39, 95% CI?=?0.16-0.91, p?=?0.031, respectively) in the training set. Using the validation set for confirmation, we found also in multivariate analysis an independent value for CSS (HR?=?0.33, 95% CI?=?0.12-0.90, p?=?0.03) and for DFS (HR?=?0.36, 95% CI?=?0.16-0.79, p?=?0.01). The estimated c-index was 0.74 using the original Kattan nomogram and 0.78 when the L/M ratio was added. Our study reports for the first time that the pre-operative L/M ratio represents a novel independent prognostic factor for prediction the clinical outcome in STS patients. This easily determinable biomarker might be helpful in improved individual risk assessment. PMID:24347236

Szkandera, Joanna; Gerger, Armin; Liegl-Atzwanger, Bernadette; Absenger, Gudrun; Stotz, Michael; Friesenbichler, Joerg; Trajanoski, Slave; Stojakovic, Tatjana; Eberhard, Katharina; Leithner, Andreas; Pichler, Martin

2014-07-15

37

Phenotypic analysis of lymphocytes and monocytes/macrophages in peripheral blood and bronchoalveolar lavage fluid from patients with pulmonary sarcoidosis  

PubMed Central

BACKGROUND—The granulomatous inflammation in sarcoidosis is driven by the interplay between T cells and macrophages. To gain a better understanding of this process the expression by these cells of cell surface activation markers, co-stimulatory molecules, and adhesion molecules was analysed.?METHODS—CD4+ and CD8+ T lymphocytes from peripheral blood (PBL) or bronchoalveolar lavage (BAL) fluid, as well as paired peripheral blood monocytes and alveolar macrophages from 27 patients with sarcoidosis were analysed by flow cytometry.?RESULTS—CD26, CD54, CD69, CD95, and gp240 were all overexpressed in T cells from BAL fluid compared with those from PBL in both the CD4+ and CD8+ subsets, while CD57 was overexpressed only in BAL CD4+ cells. In contrast, CD28 tended to be underexpressed in the BAL T cells. Monocyte/macrophage markers included CD11a, CD11b, CD11c, CD14, CD16, CD54, CD71, CD80 and CD86 and HLA class II. CD11a expression in alveolar macrophages (and peripheral blood monocytes) was increased in patients with active disease and correlated positively with the percentage of BAL lymphocytes. Expression of CD80 in macrophages correlated with the BAL CD4/CD8 ratio.?CONCLUSIONS—Our data indicate substantial activation of both CD4+ and CD8+ lung T cells in sarcoidosis. There were also increased numbers of BAL lymphocytes whose phenotypic characteristics have earlier been associated with clonally expanded, replicatively senescent cells of the Th1 type.??

Wahlstrom, J; Berlin, M; Skold, C; Wigzell, H; Eklund, A; Grunewald, J

1999-01-01

38

Lymphocyte, monocyte, and natural killer cell reference ranges in postpartal women.  

PubMed Central

Normative values for immune-cell subsets in postpartal women, who are recovering from the relative immunosuppression of pregnancy, have not been established. Considerable differences in normative values for subsets of immune cells have been demonstrated based on sociodemographic factors, such as age and race. In order to make accurate clinical decisions about postpartal women, comparisons with normal reference ranges are necessary. Therefore, flow cytometric data for 51 healthy women at 4 months postpartum are presented and changes over the first 4 postpartal months are documented. The levels of some lymphocyte cell subsets, such as CD4+/CD45RA+ and Ia on lymphocytes, remained stable over time. The levels of other lymphocyte cell subsets, such as CD4+/CD29+, increased over the first 4 postpartal months, while those of other cell subsets, such as CD8 and CD11b, increased between delivery and 2 months postpartum and then dropped again by the fourth postpartal month. The levels of two natural killer cell subsets (CD3-/CD16+ and CD3-/CD57+) rose from delivery until 1 month postpartum and then plateaued. Comparisons were made with reference ranges of nonpostpartal groups provided in the literature and in a study of healthy women being conducted in the same laboratory, and postpartal women were found to have lower values of CD8, CD3-/CD16+, CD4+/CD45RA+, CD20, and CD11b than those reported in the literature.

Gennaro, S; Fehder, W; Gallagher, P; Miller, S; Douglas, S D; Campbell, D E

1997-01-01

39

HIV1 gp41 binding to human T- and B-lymphocytes and monocytes is modulated by phorbol myristate acetate (PMA)  

Microsoft Academic Search

HIV-1 gp41 independently of CD4 binds to human T cells, B cells and monocytic cells. Since PMA downmodulates CD4 (HIV receptor) expression and inhibits HIV-1 dependent syncytia formation, we wanted to examine whether PMA could affect gp41 binding protein expression on human cells. The strong binding of HIV-1 recombinant soluble gp41 (rsgp41; Env aa539–684) to monocytes (CD14+) and B-lymphocytes (CD19+)

Ying-Hua Chen; Antje Christiansen; Manfred P. Dierich

1996-01-01

40

The Ratio of Monocytes to Lymphocytes in Peripheral Blood Correlates with Increased Susceptibility to Clinical Malaria in Kenyan Children  

PubMed Central

Background Plasmodium falciparum malaria remains a major cause of illness and death in sub-Saharan Africa. Young children bear the brunt of the disease and though older children and adults suffer relatively fewer clinical attacks, they remain susceptible to asymptomatic P. falciparum infection. A better understanding of the host factors associated with immunity to clinical malaria and the ability to sustain asymptomatic P. falciparum infection will aid the development of improved strategies for disease prevention. Methods and Findings Here we investigate whether full differential blood counts can predict susceptibility to clinical malaria among Kenyan children sampled at five annual cross-sectional surveys. We find that the ratio of monocytes to lymphocytes, measured in peripheral blood at the time of survey, directly correlates with risk of clinical malaria during follow-up. This association is evident among children with asymptomatic P. falciparum infection at the time the cell counts are measured (Hazard ratio (HR) ?=? 2.7 (95% CI 1.42, 5.01, P ?=? 0.002) but not in those without detectable parasitaemia (HR ?=? 1.0 (95% CI 0.74, 1.42, P ?=? 0.9). Conclusions We propose that the monocyte to lymphocyte ratio, which is easily derived from routine full differential blood counts, reflects an individual's capacity to mount an effective immune response to P. falciparum infection.

Warimwe, George M.; Murungi, Linda M.; Kamuyu, Gathoni; Nyangweso, George M.; Wambua, Juliana; Naranbhai, Vivek; Fletcher, Helen A.; Hill, Adrian V. S.; Bejon, Philip; Osier, Faith H. A.; Marsh, Kevin

2013-01-01

41

Antimicrobial agents induce monocytes to release IL-1 alpha, IL-6, and TNF, and induce lymphocytes to release IL-4 and TNF tau.  

PubMed

Evaluation was carried out on the action of different antibiotics on the release of cytokines. Experiments were done in vitro on monocytes and on human lymphocytes. Results show that the majority of the antibiotics tested are able to induce the release of one or more cytokines from their respective producing cells. Among the beta-lactams the most active were the cephalosporins (cephalexin, cefamandol, ceftazidin, and a sulbactam-ampicillin combination) in inducing the release of TNF, IL-1 alpha, and IL-6 from monocytes, and releasing IL-4 and IFN-tau from lymphocytes. The sulbactam-ampicillin combination and cefamandole were extremely active in the production of IFN-tau. Among the lincosamides, clindamycine notably stimulated the release of TNF and IL-6, while lincomycine induced a notable increment of IL-4 from monocytes. Teicoplanin is a very strong inducer of TNF, IL-1 alpha and IL-6. PMID:1294622

Tufano, M A; Cipollaro de l'Ero, G; Ianniello, R; Baroni, A; Galdiero, F

1992-01-01

42

The automated monocyte count is independently predictive of overall survival from diagnosis in chronic lymphocytic leukaemia and of survival following first-line chemotherapy.  

PubMed

We conducted an analysis of the effect of monocytosis at diagnosis of CLL on subsequent overall (OS) and treatment-free survival (TFS). Monocyte counts were performed using the Sysmex XE2100 analyser. A monocyte count >0.9 × 10(9)L(-1) at the time of diagnosis was associated with a shortened OS and TFS. Monocytosis at diagnosis was associated with lymphocyte count, deletions of chromosomes 17p and 11q, the extent of IgVH somatic hypermutation and Binet stage. A multivariate analysis model which excluded somatic hypermutation found only monocyte count and age to be independently predictive of OS. The automated monocyte count is predictive of OS and TFS in newly diagnosed CLL. PMID:23522450

Mazumdar, Ranjana; Evans, Paul; Culpin, Rachel; Bailey, James; Allsup, David

2013-06-01

43

Ratio of Monocytes to Lymphocytes in Peripheral Blood Identifies Adults at Risk of Incident Tuberculosis Among HIV-Infected Adults Initiating Antiretroviral Therapy  

PubMed Central

Background.?Eight decades ago, the ratio of monocytes to lymphocytes (hereafter, the “ML ratio”) was noted to affect outcomes of mycobacterial infection in rabbits. Recent transcriptomic studies support a role for relative proportions of myeloid and lymphoid transcripts in tuberculosis outcomes. The ML ratio in peripheral blood is known to be governed by hematopoietic stem cells with distinct biases. Methods.?The predictive value of the baseline ML ratio was modeled in 2 prospective cohorts of HIV-infected adults starting cART in South Africa (primary cohort, 1862 participants; replication cohort, 345 participants). Incident tuberculosis was diagnosed with clinical, radiographic, and microbiologic methods per contemporary guidelines. Kaplan-Meier survival analyses and Cox proportional hazards modeling were conducted. Results.?The incidence rate of tuberculosis differed significantly by baseline ML ratio: 32.61 (95% confidence interval [CI], 15.38–61.54), 16.36 (95% CI, 12.39–21.23), and 51.80 (95% CI, 23.10–101.71) per 1000 patient-years for ML ratios of less than the 5th percentile, between the 5th and 95th percentiles, and greater than the 95th percentile, respectively (P = .007). Neither monocyte counts nor lymphocyte counts alone were associated with tuberculosis. After adjustment for sex, World Health Organization human immunodeficiency virus disease stage, CD4+ T-cell counts, and previous history of tuberculosis, hazards of disease were significantly higher for patients with ML ratios of less than the 5th percentile or greater than the 95th percentile (adjusted hazard ratio, 2.47; 95% CI, 1.39–4.40; P = .002). Conclusions.?The ML ratio may be a useful, readily available tool to stratify the risk of tuberculosis and suggests involvement of hematopoietic stem cell bias in tuberculosis pathogenesis.

Naranbhai, Vivek; Hill, Adrian V. S.; Abdool Karim, Salim S.; Naidoo, Kogieleum; Abdool Karim, Quarraisha; Warimwe, George M.; McShane, Helen; Fletcher, Helen

2014-01-01

44

Phenotypic and cytologic studies of lymphoid cells and monocytes in primary culture of porcine bone marrow during infection of African swine fever virus.  

PubMed

We have modeled in vitro infection of African swine fever virus (ASFV) in primary unstimulated cells of the porcine bone marrow and have studied the phenotypical changes in the population of porcine lymphoid cells by cytophotometry. Monocytes and large-sized lymphocytes completely vanished in 72 h of infection which is result of high sensitivity of those cells to ASFV. We describe DNA synthesis in monocytes at 24 h post infection. Cytophotometry of the uninfected cells revealed the few number of atypical lymphocytes and lymphoblasts after 72 h of cultivation; whereas in viral infected cultures, atypical cells appeared in large quantity (about 14%) with 24 h. Most of atypical lymphocytes and lymphoblasts had altered nucleus, and only a small number of atypical cells had additional nucleus. The cytophotometry of main and additional nuclei showed that DNA content didn't exceed diploid standard which indicates that the additional nuclei were consequence of fragmentation of nuclei in lymphocytes. PMID:21184199

Karalova, E M; Sargsyan, Kh V; Hampikian, G K; Voskanyan, H E; Abroyan, L O; Avetisyan, A S; Hakobyan, L A; Arzumanyan, H H; Zakaryan, H S; Karalyan, Zaven A

2011-03-01

45

Immunomagnetic selection of purified monocyte and lymphocyte populations from peripheral blood mononuclear cells following cryopreservation.  

PubMed Central

Cryopreservation is a method commonly used to store human blood samples. We sought to determine if cryopreserved peripheral blood mononuclear cells (PBMC) could be separated effectively into distinct populations by using monoclonal antibodies and immunomagnetic microspheres. PBMC obtained from healthy blood donors and from human immunodeficiency virus-infected subjects were cryopreserved for as long as 18 months. Recovered cells were separated into CD14+ monocytes and CD4+ T-cell subsets by immunomagnetic selection. Flow cytometry analysis indicated >95% depletion of monocytes from PBMC following immunomagnetic selection with anti-CD14. A highly enriched population of CD4+ T cells was obtained from the CD14-depleted cell fraction by using an anti-CD4 monoclonal antibody and detachable immunomagnetic beads. The CD4+ T cells were subsequently separated into CD4+ CD45RO and CD4+ CD45RA fractions. Each fraction contained >90% enrichment for the respective subpopulation and <5% of the reciprocal subpopulation. No significant differences in cell surface expression of leukocyte markers, in efficiency of selection of PBMC subpopulations, or in mitogen-induced proliferation were detected in freshly isolated or cryopreserved cells. Efficient recovery of cryopreserved specimens means that targeted assays can be performed on selected, prospectively stored samples once clinical endpoints have been achieved.

Sleasman, J W; Leon, B H; Aleixo, L F; Rojas, M; Goodenow, M M

1997-01-01

46

Induction of PD-L1 on monocytes: A new mechanism by which IVIg inhibits mixed lymphocyte reactions.  

PubMed

Allograft rejection and graft-versus-host disease (GvHD) are frequent complications following solid organ or stem cell transplantation in which T cell activation plays a central role. Despite the development of new immunosuppressive drugs that improve the success rate of transplantation, allograft survival continues to be a challenge. Recently, intravenous immunoglobulin (IVIg) has been proposed as prophylaxis and post-transplant treatment to reduce acute rejection episodes. IVIg is a therapeutic agent that is known to down-modulate T cell functions in patients with autoimmune disorders. To test the hypothesis that this immunomodulatory effect could be beneficial in the context of transplantation, we used mixed lymphocyte reactions (MLR) as an in vitro model of allograft rejection and GvHD. Our results show that IVIg strongly inhibits the MLR as evaluated by IL-2 secretion, a well-known marker of T cell activation. IVIg also modulates the secretion of other pro-(IL-6, IFN-?) and anti-inflammatory (IL-1RA) cytokines. More importantly, we show that IVIg induces monocytes with a CD80(low) PD-L1(high) phenotype and that blockade of PD-L1 partially abrogates the inhibitory effect of IVIg. We have thus identified a new mechanism by which IVIg inhibits T cell functions in the context of transplantation, supporting the potential usefulness of IVIg in the prevention or treatment of graft rejection and GvHD. PMID:24875729

Padet, Lauriane; Loubaki, Lionel; Bazin, Renée

2014-09-01

47

Low lymphocyte-to-monocyte ratio predicts unfavorable prognosis in non-germinal center type diffuse large B-cell lymphoma.  

PubMed

The peripheral blood lymphocyte to monocyte ratio (LMR) at diagnosis has been used to predict survival in diffuse large B-cell lymphoma (DLBCL) patients, but its prognostic significance with respect to different cell-of-origin (COO) subtypes remains unknown. We retrospectively analyzed 168 de novo DLBCL patients in this study and found that a low LMR (?2.6) correlates with B symptoms, elevated LDH, advanced Ann Arbor stage and higher international prognostic index (IPI) score (p<0.05). The low LMR is a negative prognostic parameter for overall survival (OS) and event-free survival (EFS) in non-germinal center (GC) type DLBCL patients, as compared with the high LMR, especially in those treated with R-CHOP. However, the LMR has less correlation with the OS and EFS in GC type DLBCL patients (p=0.545 and 0.547, respectively). Multivariate analysis adjusting for IPI revealed that the low LMR indicates a shorter survival retain both OS and EFS in non-GC subtypes (p=0.023 and 0.005, respectively). In the non-GC DLBCL patients treated with R-CHOP a low LMR still showed a trend to predict poor EFS (p=0.052). In conclusion, these data suggest that a low LMR at diagnosis may imply a poor prognosis in non-GC subtype DLBCL patients, especially in those treated with R-CHOP, but not in those GC subtype DLBCL patients. PMID:24713260

Wei, Xiaolei; Huang, Fen; Wei, Yongqiang; Jing, Hui; Xie, Muchen; Hao, Xiaoxiao; Feng, Ru

2014-06-01

48

Ratio of peripheral blood absolute lymphocyte count to absolute monocyte count at diagnosis is associated with progression-free survival in follicular lymphoma.  

PubMed

The prognosis of follicular lymphoma (FL) is significantly associated with host immunity and tumor microenvironment. Lymphopenia has been identified as a negative prognostic factor for FL. The association between monocytosis and progression-free survival (PFS) in FL remains controversial. It is unknown whether the ratio of peripheral blood absolute lymphocyte count to absolute monocyte count (ALC/AMC) at diagnosis is associated with FL prognosis. We studied 99 consecutive patients with FL who were treated with rituximab-containing chemotherapy at Kitano Hospital or Kyoto University Hospital between 2000 and 2012. We analyzed individual variables associated with the ALC/AMC ratio before treatment, as well as known prognostic factors of FL, and found that an ALC/AMC ratio of 4.7 was the best cut-off value for PFS. Kaplan-Meier analysis showed that a decreased ALC/AMC ratio was associated with inferior PFS (P = 0.022). Multivariate analysis showed that a decreased ALC/AMC ratio was a significant poor prognostic factor independent of other variables (hazard ratio, 2.714; 95 % confidence interval, 1.060-6.948; P = 0.037). The ALC/AMC ratio before treatment may be a significant prognostic factor predicting PFS of FL. PMID:24756873

Kumagai, Shogo; Tashima, Masaharu; Fujikawa, Jun; Iwasaki, Makoto; Iwamoto, Yoshihiro; Sueki, Yuki; Fukunaga, Akiko; Yanagita, Soshi; Nishikori, Momoko; Takaori-Kondo, Akifumi; Arima, Nobuyoshi

2014-06-01

49

Infection of human monocytes by Chlamydia pneumoniae and Chlamydia trachomatis: an in vitro comparative study  

PubMed Central

Background An increasing number of studies suggest that chlamydiae can infect immune cells. The altered immune cell function could contribute to the progression of several chronic inflammatory diseases. The aim of this study was to comparatively evaluate Chlamydia pneumoniae (CP) and Chlamydia trachomatis (CT) interactions with in vitro infected human blood monocytes. Results Fresh isolated monocytes were infected with viable CP and CT elementary bodies and infectivity was evaluated by recultivating disrupted monocytes in permissive epithelial cells. The production of reactive oxygen and nitrogen species was studied in the presence of specific fluorescent probes. Moreover, TNF-?, INF-?, INF-? and INF-? gene expression was determined. CT clearance from monocytes was complete at any time points after infection, while CP was able to survive up to 48 hours after infection. When NADPH oxydase or nitric oxide synthase inhibitors were used, CT infectivity in monocytes was restored, even if at low level, and CT recovery’s rate was comparable to CP one. CT-infected monocytes produced significantly higher levels of reactive species compared with CP-infected monocytes, at very early time points after infection. In the same meanwhile, TNF-? and INF-? gene expression was significantly increased in CT-infected monocytes. Conclusions Our data confirm that CP, but not CT, is able to survive in infected monocytes up to 48 hours post-infection. The delay in reactive species and cytokines production by CP-infected monocytes seems to be crucial for CP survival.

2014-01-01

50

Isolation of Human Mononuclear Cell Subsets by Counterflow Centrifugal Elutriation (CCE). II. Functional Properties of B-Lymphocyte-, T-Lymphocyte-, and Monocyte-Enriched Fractions.  

National Technical Information Service (NTIS)

Counterflow centrifugal elutriation (CCE)), a technique which separates cells by size and density, was used to seperate human peripheral blood mononuclear cells into fractions enriched for T lymphocytes, B lymphocytes. These morphologically and phenotypic...

L. M. Wahl I. M. Katona B. M. Stadler R. L. Wilder W. E. Helsel

1984-01-01

51

Studies on the metabolism of triphenylphosphate by carboxylesterases and human monocytes  

SciTech Connect

Resin workers exposed to triphenylphosphate (TPP), an organophosphate (OP) flame retardant and plasticizer, had a decreased expression of carboxylesterase (CBE) activity in their peripheral blood monocytes. The mechanisms of CBE inhibition by TPP were investigated using purified hog liver CBE and intact human monocytes. TPP inactivated hog liver CBE in a time and dose dependent manner, and this inhibition was partially reversed by alkaline phosphatase (AP). Analysis of ({sup 14}C)TPP metabolites from the enzymatic reaction by high performance liquid chromatography (HPLC) and gas chromatography/mass spectrometry (GM-C) identified phenol as the hydrolytic metabolite of TPP. Human monocytes cultured with ({sup 14}C)TPP also released phenol. In addition to phenol, several phenol metabolites, such as catechol, hydroquinone, 2,2 biphenol and 4,4 biphenol were also generated by monocytes. An identical pattern of these metabolites was also formed from monocytes incubated with radiolabelled phenol. This cellular degradation of TPP was inhibited by diisopropylfluorophosphate (DFP), but not observed in neutrophil or lymphocyte cultures. Activation of monocytes with gamma interferon (IFN-g), f-Met-Leu-Phe, and serum treated zymosan (STZ) enhanced the levels of phenolic metabolites and, further, shifted the metabolism of TPP towards the formation of the biphenolic metabolites.

Paxman, D.G. III.

1988-01-01

52

A study of porcine lymphocyte populations. I. Separation of porcine lymphocyte subpopulations.  

PubMed

Several methods for separating porcine lymphocyte populations were studied. Lymphocyte populations enriched in T cells were obtained by filtration on nylon fiber columns. Lymphocyte populations enriched in B cells were obtained by E rosette sedimentation. Results obtained with anti-immunoglobulin columns were less satisfactory. Attempts to fractionate porcine lymphoid cells with the help of Helix pomatia lectin remained unsuccessful. PMID:15615056

Buschmann, H; Pawlas, S

1980-08-01

53

Arachidonic acid metabolism by human monocytes. Studies with platelet- depleted cultures  

PubMed Central

Purified human monocytes release and metabolize endogenous arachidonic acid (20:4) from phospholipid stores when challenged with particulate inflammatory stimuli or the calcium ionophore A23187. Using radiolabeled cultures, the percentage of total [3H]20:4 released was similar with each type of stimulus. However, the spectrum of 20:4 metabolites differed. With opsonized zymosan (OpZ) or Sephadex beads coated with IgG immune complexes (Ig-beads), the predominant product was thromboxane (25% of the total) together with smaller amounts of other cyclo-oxygenase products and lipoxygenase metabolites. Levels of thromboxane synthesis by monocytes were comparable to those by platelets, as measured by radioimmunoassay. In contrast, exposure to the nonspecific agent A23187 led to mainly lipoxygenase products (70% of the total). Monocytes isolated from mononuclear cell fractions of peripheral blood contain platelets specifically rosetted to their surfaces. These platelet contaminants were removed by sequential incubations of monocytes in serum and EDTA followed by adherence and detachment from tissue culture vessels. The presence of platelets in routinely isolated monocytes presented a major difficulty in the study of human monocyte 20:4 metabolism since platelets also synthesize thromboxane. Loss of 12-HETE synthesis (16-fold reduction relative to 5- HETE) in A23187-stimulated cultures provided a convenient measure of platelet depletion. This together with the response to monocyte- specific stimuli (OpZ and Ig-beads) allowed for the distinction between monocyte and platelet 20:4 metabolism.

1983-01-01

54

Monocytic AML cells inactivate antileukemic lymphocytes: role of NADPH oxidase/gp91phox expression and the PARP-1/PAR pathway of apoptosis  

PubMed Central

Dysfunction of T cells and natural killer (NK) cells has been proposed to determine the course of disease in acute myeloid leukemia (AML), but only limited information is available on the mechanisms of lymphocyte inhibition. We aimed to evaluate to what extent human malignant AML cells use NADPH oxidase-derived reactive oxygen species (ROS) as an immune evasion strategy. We report that a subset of malignant myelomonocytic and monocytic AML cells (French-American-British [FAB] classes M4 and M5, respectively), recovered from blood or BM of untreated AML patients at diagnosis, expressed the NADPH oxidase component gp91phox. Highly purified FAB M4/M5 AML cells produced large amounts of ROS on activation and triggered poly-[ADP-ribose] polymerase-1?dependent apoptosis in adjacent NK cells, CD4+ T cells, and CD8+ T cells. In contrast, immature (FAB class M1) and myeloblastic (FAB class M2) AML cells rarely expressed gp91phox, did not produce ROS, and did not trigger NK or T-cell apoptosis. Microarray data from 207 AML patients confirmed a greater expression of gp91phox mRNA by FAB-M4/M5 AML cells than FAB-M1 cells (P < 10?11) or FAB-M2 cells (P < 10?9). Our data are suggestive of a novel mechanism by which monocytic AML cells evade cell-mediated immunity.

Aurelius, Johan; Thoren, Fredrik B.; Akhiani, Ali A.; Brune, Mats; Palmqvist, Lars; Hansson, Markus; Martner, Anna

2012-01-01

55

Virus-specific HLA-restricted lysis of herpes simplex virus-infected human monocytes and macrophages mediated by cytotoxic T lymphocytes  

SciTech Connect

Freshly-isolated peripheral blood human monocytes and 5 day in vitro cultured macrophages were infected with herpes simplex virus type 1 (HSV-1), labeled with /sup 51/Cr, and used as target cells in a 12-14 hour cell-mediated cytotoxicity assay. Mononuclear leukocytes (MNL) from HSV-1 non-immune individuals, whether unstimulated or stimulated with HSV-1 antigen, did not mediate significant lysis of either target cell. HSV-immune MNL, both freshly-isolated and cultured for 5 days without antigen, demonstrated only low levels of natural killer (NK) cell-mediate lysis. MNL from HSV-immune individuals incubated for 5 days in vitro with HSV-1 antigen mediated significant virus-specific lysis of both target cells. Mean virus-specific lysis of autologous monocytes was 8.5(/+-/2.0)% compared to a three-fold greater virus-specific lysis of autologous macrophages. Greater than 70% of this lytic activity was mediated by Leu-11-negative, T3-positive cytotoxic T lymphocytes (CTL). Allogeneic target cells lacking a common HLA determinant were not significantly lysed while T8-positive CTL mediated infrequent lysis of target cells sharing a common HLA-A and/or HLA-B determinant. T4-positive lymphocytes were demonstrated to be the predominant cell mediating lysis of autologous target cells and allogeneic target cells sharing both HLA-A and/or HLA-B plus HLA-DR determinants with the CTL; the T4-positive cell was the sole CTL mediator of lysis of allogeneic target cells having a common HLA-DR determinant.

Torpey, D.J. III

1987-01-01

56

Colorectal Cancer Cells Induce Lymphocyte Apoptosis by an Endothelial Monocyte-Activating Polypeptide-II-Dependent Mechanism1  

Microsoft Academic Search

Endothelial monocyte-activating polypeptide-II (EMAP-II) was first isolated from cell growth medium conditioned by tumor cells, and is closely related or identical with the p43 component of the mammalian multisynthase complex. In its secreted form, EMAP-II has multiple cytokine-like activities in vitro, inducing procoagulant activity on the surface of endothelial cells, increasing expres- sion of E- and P-selectins and TNF-R1, and

J. Clifford Murray; Peter Symonds; Wynne Ward; Mary Huggins; Anna Tiga; Katherine Rice; Yee M. Heng; Ian Todd; R. Adrian Robins

57

X-linked adrenoleukodystrophy: very long-chain fatty acid metabolism is severely impaired in monocytes but not in lymphocytes.  

PubMed

X-linked adrenoleukodystrophy (X-ALD) is a fatal neurodegenerative disease caused by mutations in the ABCD1 gene, encoding a member of the peroxisomal ABC transporter family. The ABCD1 protein transports CoA-activated very long-chain fatty acids (VLCFAs) into peroxisomes for degradation via ?-oxidation. In the severest form, X-ALD patients suffer from inflammatory demyelination of the brain. As the extent of the metabolic defect in the main immune cells is unknown, we explored their phenotypes concerning mRNA expression pattern of the three peroxisomal ABC transporters, VLCFA accumulation and peroxisomal ?-oxidation. In controls, ABCD1 expression was high in monocytes, intermediate in B cells and low in T cells; ABCD2 expression was extremely low in monocytes, intermediate in B cells and highest in T cells; ABCD3 mRNA was equally distributed. In X-ALD patients, the expression patterns remained unaltered; accordingly, monocytes, which lack compensatory VLCFA transport by ABCD2, displayed the severest biochemical phenotype with a 6-fold accumulation of C26:0 and a striking 70% reduction in peroxisomal ?-oxidation activity. In contrast, VLCFA metabolism was close to control values in B cells and T cells, supporting the hypothesis that sufficient ABCD2 is present to compensate for ABCD1 deficiency. Thus, the vulnerability of the main immune cell types is highly variable in X-ALD. Based on these results, we propose that in X-ALD the halt of inflammation after allogeneic hematopoietic stem cell transplantation relies particularly on the replacement of the monocyte lineage. Additionally, these findings support the concept that ABCD2 is a target for pharmacological induction as an alternative therapeutic strategy. PMID:24363066

Weber, Franziska D; Wiesinger, Christoph; Forss-Petter, Sonja; Regelsberger, Günther; Einwich, Angelika; Weber, Willi H A; Köhler, Wolfgang; Stockinger, Hannes; Berger, Johannes

2014-05-15

58

Allergy or Tolerance: Reduced Inflammatory Cytokine Response and Concomitant IL-10 Production of Lymphocytes and Monocytes in Symptom-Free Titanium Dental Implant Patients  

PubMed Central

Hypersensitivity reactions to titanium (Ti) are very rare. Thus, we assessed the proinflammatory response and also potential tolerance favoring in vitro reactivity of human blood lymphocytes and monocytes (PBMC) to Ti in healthy individuals (14 without, 6 with complication-free dental Ti implants). The proliferation index (SI) in lymphocyte transformation test (LTT) and production of cytokines linked to innate immune response (IL-1?, IL-6, and TNF?) or immune regulation (IL-10) were assessed in response to TiO2 particles or Ti discs. In both groups, the Ti-LTT reactivity was not enhanced (e.g., SI < 3). The control antigen tetanus toxoid (TT) gave adequate reactivity (median SI individuals without/with implant: 20.6 ± 5.97/19.58 ± 2.99). Individuals without implant showed higher cytokine response to Ti materials than individuals with symptom-free implants; for example, TiO2 rutile particle induced increase of IL-1? 70.27-fold/8.49-fold versus control medium culture. PBMC of 5 of the 6 individuals with complication-free Ti implants showed an ex vivo ongoing production of IL-10 (mean 4.18 ± 2.98?pg/mL)-but none of the 14 controls showed such IL-10 production. Thus in vitro IL-1?-, IL-6-, and TNF-? production reflects “normal” unspecific immune response to Ti. This might be reduced by production of tolerogenic IL-10 in individuals with symptom-free Ti dental implants.

Thomas, Peter; Wollenberg, Andreas

2013-01-01

59

Intraglomerular T cells and monocytes in nephritis: Study with monoclonal antibodies  

Microsoft Academic Search

Glomerular T cells and monocytes in nephritis: study with monoclonal antibodies. Intraglomerular T cells, monocytes, total leucocytes and other mononuclear subsets were sought in renal biopsies from patients with glomerulonephritis, using monoclonal antibodies and immunoperoxidase techniques. Twenty–four biopsies with no significant glomerular proliferation on optical microscopy, thirty–two with only endocapillary hypercellularity, and twenty–one with extra capillary crescentic glomerular disease were

Fernando E B Nolasco; John Stewart Cameron; Barrie Hartley; Adolfo Coelho; Gillian Hildreth; Rowena Reuben

1987-01-01

60

Activated T lymphocytes suppress osteoclastogenesis by diverting early monocyte/macrophage progenitor lineage commitment towards dendritic cell differentiation through down-regulation of receptor activator of nuclear factor-kappaB and c-Fos.  

PubMed

Activated T lymphocytes either stimulate or inhibit osteoclastogenesis from haematopoietic progenitors in different experimental models. To address this controversy, we used several modes of T lymphocyte activation in osteoclast differentiation--mitogen-pulse, anti-CD3/CD28 stimulation and in vivo and in vitro alloactivation. Osteoclast-like cells were generated from non-adherent immature haematopoietic monocyte/macrophage progenitors in murine bone-marrow in the presence of receptor activator of nuclear factor (NF)-kappaB ligand (RANKL) and monocyte-macrophage colony-stimulating factor (M-CSF). All modes of in vivo and in vitro T lymphocyte activation and both CD4(+) and CD8(+) subpopulations produced similar inhibitory effects on osteoclastogenesis paralleled by enhanced dendritic cell (DC) differentiation. Osteoclast-inhibitory effect was associated with T lymphocyte activation and not proliferation, and could be replaced by their culture supernatants. The stage of osteoclast differentiation was crucial for the inhibitory action of activated T lymphocytes on osteoclastogenesis, because the suppressive effect was visible only on early osteoclast progenitors but not on committed osteoclasts. Inhibition was associated specifically with increased granulocyte-macrophage colony-stimulating factor (GM-CSF) expression by the mechanism of progenitor commitment toward lineages other than osteoclast because activated T lymphocytes down-regulated RANK, CD115, c-Fos and calcitonin receptor expression, and increased differentiation towards CD11c-positive DC. An activated T lymphocyte inhibitory role in osteoclastogenesis, confirmed in vitro and in vivo, mediated through GM-CSF release, may be used to counteract activated bone resorption mediated by T lymphocyte-derived cytokines in inflammatory and immune disorders. We also demonstrated the importance of alloactivation in osteoclast differentiation and the ability of cyclosporin A to abrogate T lymphocyte inhibition of osteoclastogenesis, thereby confirming the functional link between alloreaction and bone metabolism. PMID:16968409

Grcevi?, D; Luki?, I K; Kovaci?, N; Ivcevi?, S; Katavi?, V; Marusi?, A

2006-10-01

61

Activated T lymphocytes suppress osteoclastogenesis by diverting early monocyte/macrophage progenitor lineage commitment towards dendritic cell differentiation through down-regulation of receptor activator of nuclear factor-kappaB and c-Fos  

PubMed Central

Activated T lymphocytes either stimulate or inhibit osteoclastogenesis from haematopoietic progenitors in different experimental models. To address this controversy, we used several modes of T lymphocyte activation in osteoclast differentiation ? mitogen-pulse, anti-CD3/CD28 stimulation and in vivo and in vitro alloactivation. Osteoclast-like cells were generated from non-adherent immature haematopoietic monocyte/macrophage progenitors in murine bone-marrow in the presence of receptor activator of nuclear factor (NF)-?B ligand (RANKL) and monocyte–macrophage colony-stimulating factor (M-CSF). All modes of in vivo and in vitro T lymphocyte activation and both CD4+ and CD8+ subpopulations produced similar inhibitory effects on osteoclastogenesis paralleled by enhanced dendritic cell (DC) differentiation. Osteoclast-inhibitory effect was associated with T lymphocyte activation and not proliferation, and could be replaced by their culture supernatants. The stage of osteoclast differentiation was crucial for the inhibitory action of activated T lymphocytes on osteoclastogenesis, because the suppressive effect was visible only on early osteoclast progenitors but not on committed osteoclasts. Inhibition was associated specifically with increased granulocyte–macrophage colony-stimulating factor (GM-CSF) expression by the mechanism of progenitor commitment toward lineages other than osteoclast because activated T lymphocytes down-regulated RANK, CD115, c-Fos and calcitonin receptor expression, and increased differentiation towards CD11c-positive DC. An activated T lymphocyte inhibitory role in osteoclastogenesis, confirmed in vitro and in vivo, mediated through GM-CSF release, may be used to counteract activated bone resorption mediated by T lymphocyte-derived cytokines in inflammatory and immune disorders. We also demonstrated the importance of alloactivation in osteoclast differentiation and the ability of cyclosporin A to abrogate T lymphocyte inhibition of osteoclastogenesis, thereby confirming the functional link between alloreaction and bone metabolism.

Grcevic, D; Lukic, I K; Kovacic, N; Ivcevic, S; Katavic, V; Marusic, A

2006-01-01

62

Corticosteroid-resistant bronchial asthma is associated with increased c-fos expression in monocytes and T lymphocytes.  

PubMed Central

Unstimulated peripheral blood mononuclear cells (PBMCs) from corticosteroid-resistant (CR) but not corticosteroid-sensitive (CS) asthmatics demonstrate increased activating peptide-1 (AP-1)- and decreased glucocorticoid receptor (GR)-DNA binding. We test whether these abnormalities are associated with excessive generation of c-fos, the inducible component of AP-1. The c-fos transcription rate, mRNA and protein levels, and GR-DNA binding were quantitated in PBMCs, T cells, and monocytes from CS, CR, and nonasthmatic subjects. There was a 1.7-, 4.2-, and 2.3-fold greater increase in the baseline c-fos transcription rate, mRNA expression, and protein levels, respectively, in PBMCs derived from CR compared with CS patients. At optimal stimulation with PMA, there was a 5.7-, 3.4-, and 2-fold greater increase in the c-fos transcription rate, mRNA accumulation, and protein levels, respectively, in CR compared with CS PBMCs. These abnormalities were detected in both the T cell and monocyte subpopulations. PMA stimulation converted PBMCs from a CS to a CR phenotype and was associated with direct interaction between c-Fos and the GR. Pretreatment of PBMCs from CR patients with c-fos antisense oligonucleotides enhanced GR-DNA binding activity in CR PBMCs stimulated with dexamethasone. We suggest that increased c-fos synthesis provides a major mechanism for the increased AP-1- and decreased GR- DNA binding seen in CR asthma.

Lane, S J; Adcock, I M; Richards, D; Hawrylowicz, C; Barnes, P J; Lee, T H

1998-01-01

63

HIV-1 regulation of latency in the monocyte-macrophage lineage and in CD4+ T lymphocytes.  

PubMed

The introduction in 1996 of the HAART raised hopes for the eradication of HIV-1. Unfortunately, the discovery of latent HIV-1 reservoirs in CD4+ T cells and in the monocyte-macrophage lineage proved the optimism to be premature. The long-lived HIV-1 reservoirs constitute a major obstacle to the eradication of HIV-1. In this review, we focus on the establishment and maintenance of HIV-1 latency in the two major targets for HIV-1: the CD4+ T cells and the monocyte-macrophage lineage. Understanding the cell-type molecular mechanisms of establishment, maintenance, and reactivation of HIV-1 latency in these reservoirs is crucial for efficient therapeutic intervention. A complete viral eradication, the holy graal for clinicians, might be achieved by strategic interventions targeting latently and productively infected cells. We suggest that new approaches, such as the combination of different kinds of proviral activators, may help to reduce dramatically the size of latent HIV-1 reservoirs in patients on HAART. PMID:19801499

Redel, Laetitia; Le Douce, Valentin; Cherrier, Thomas; Marban, Céline; Janossy, Andrea; Aunis, Dominique; Van Lint, Carine; Rohr, Olivier; Schwartz, Christian

2010-04-01

64

A phase I first-in-human study with tefinostat - a monocyte/macrophage targeted histone deacetylase inhibitor - in patients with advanced haematological malignancies.  

PubMed

Tefinostat (CHR-2845) is a monocyte/macrophage targeted histone deacetylase inhibitor (HDACi). This first-in-human, standard 3 + 3 dose escalating trial of oral, once daily tefinostat was conducted to determine the safety, tolerability, pharmacokinetic and pharmacodynamic profile of tefinostat in relapsed/refractory haematological diseases. Eighteen patients were enrolled at doses of 20-640 mg. Plasma concentrations of tefinostat exceeded those demonstrated to give in vitro anti-proliferative activity. Flow cytometric pharmacodynamic assays demonstrated monocyte-targeted increases in protein acetylation, without corresponding changes in lymphocytes. Dose-limiting toxicities (DLTs) were not observed and dose escalation was halted at 640 mg without identification of the maximum tolerated dose. Drug-related toxicities were largely Common Toxicity Criteria for Adverse Events grade 1/2 and included nausea, anorexia, fatigue, constipation, rash and increased blood creatinine. A patient with chronic monomyelocytic leukaemia achieved a bone marrow response, with no change in peripheral monocytes. An acute myeloid leukaemia type M2 patient showed a >50% decrease in bone marrow blasts and clearance of peripheral blasts. In conclusion, tefinostat produces monocyte-targeted HDACi activity and is well tolerated, without the DLTs, e.g. fatigue, diarrhoea, thrombocytopenia, commonly seen with non-targeted HDACi. The early signs of efficacy and absence of significant toxicity warrant further evaluation of tefinostat in larger studies. (clinicaltrials.gov identifier: NCT00820508). PMID:23647373

Ossenkoppele, Gert J; Lowenberg, Bob; Zachee, Pierre; Vey, Norbert; Breems, Dimitri; Van de Loosdrecht, Arjan A; Davidson, Alan H; Wells, Graham; Needham, Lindsey; Bawden, Lindsay; Toal, Martin; Hooftman, Leon; Debnam, Phillip M

2013-07-01

65

Effect of Salmonella-infected human monocytes on natural killer cell cytotoxicity. In vitro studies.  

PubMed

Various chemicals, including some bacteria-derived components, modulate natural killer cell (NKC) activity. We have analyzed the effect of wild-type Ty2 and of mutant strain TYT1231 Salmonella typhi-infected monocytes (U937 cells and human autologous monocytes) on NKC cytotoxicity of peripheral blood mononuclear cell (PBMC) and highly purified NKC (HPNKC; CD16+/56+ > 95%; the rest corresponding to CD3+ T-cells). PBMC's co-culture with either S. typhi strain infected U937 cells (medium or non-infected U937 cells as controls) resulted in the induction of lymphocyte activated killer (LAK) cell activity showing cytotoxicity against target human NKC-resistant lymphoblastoid Daudi cell line. Comparable experiments using autologous monocytes gave similar results. Co-culture of HPNKC preparations with either S. typhi strain infected U937 cells resulted in increased LAK cell activity against target Daudi cells in each and everyone of the five samples tested; paired Student's t-test p < 0.01 for both times (20 and 40 h) tested. Similar to the results observed in the experiments using PBMC, we did not find significant differences in the ability between medium and non-infected cells, or between wild-type S. typhi Ty2 and mutant strain TYT1231 infected U937 cells, to induce LAK activity in HPNKC preparations. PBMC co-incubation with either S. typhi strain infected U937 cells or autologous monocytes resulted in significant increases in IL-12, TNF-alpha, and IFN-gamma secretion. In similar experiments using HPNKC samples instead, infected U937 cells significantly increased IL-12 and IFN-gamma, but not TNF-alpha secretion. PBMC co-incubation with non-infected U937 cells, but not with non-infected monocytes, significantly increased supernatant IL-12 and TNF-alpha levels (no significant changes in IFN-gamma were recorded). Secreted cytokines remained essentially unchanged after co-incubating HPNKC preparation with non-infected U-937 cells. Incubation of PBMC or HPNKC preparations with either S. typhi strain infected U937 cells failed to produce significant changes in the expression of NKC lineage (CD16+/56+) or activation (CD28+, CD69+ and CD95+) markers. The ability of infected monocytes to induce LAK activity, release NKC cytokines and upmodulate NKC's CD95+ marker expression was essentially the same for both infecting Salmonella strains used. These results suggest a role for NKC in the physiological defensive response against intracellularly infected monocytes representing, perhaps one of the earliest antimicrobial mechanisms of the innate immune system. PMID:11460309

Blanco, L; Puente, J; Carrasco, C; Miranda, D; Wolf, M E; Mosnaim, A D

2001-07-01

66

The marginal blood pool of the rat contains not only granulocytes, but also lymphocytes, NK-cells and monocytes: a second intravascular compartment, its cellular composition, adhesion molecule expression and interaction with the peripheral blood pool.  

PubMed

To leave the blood, leucocytes marginate to the vessel wall. Granulocytes thereby form the so-called marginal pool. It is unclear to what extent such a second intravascular compartment also exists for lymphocytes subsets, NK-cells and monocytes. Samples of the peripheral blood and the marginal pool of the LEW rat were analysed by flow cytometry. In the marginal pool the percentage of granulocytes and monocytes was significantly higher compared to that of the peripheral blood, and the proportion of 'naive' T and B lymphocytes was decreased. The expression of LFA-1 was higher on all leucocyte subsets of the marginal pool except the granulocytes, whereas no differences were seen for the expression of other adhesion molecules (alpha 4-integrins, ICAM-1, CD2, L-selectin, and CD44). In addition, splenectomy influenced the cellular composition of peripheral blood and marginal pool differently and, after injection of blood leucocytes, these cells were found in both compartments showing its characteristic cellular composition. Thus, not only granulocytes, but also B and T lymphocyte subsets, NK-cells and monocytes form a second distinct intravascular compartment. This marginal pool probably influences the cellular composition of leucocyte subsets available for entry into the tissues. PMID:8947597

Klonz, A; Wonigeit, K; Pabst, R; Westermann, J

1996-11-01

67

Kisspeptin Effect on Endothelial Monocyte Activating Polypeptide II (EMAP-II)-Associated Lymphocyte Cell Death and Metastases in Colorectal Cancer Patients  

PubMed Central

Kisspeptin is an antimetastatic agent in some cancers that has also been associated with lymphoid cell apoptosis, a phenomenon favoring metastases. Our aim was to determine the association of kisspeptin with lymphocyte apoptosis and the presence of metastases in colorectal cancer patients. Blood was drawn from 69 colon cancer patients and 20 healthy volunteers. Tissue specimens from healthy and pathological tissue were immunohistochemically analyzed for kisspeptin and endothelial monocyte activating polypeptide II (EMAP-II) expression. Blood EMAP-II and soluble Fas ligand (sFasL) levels were examined by an enzyme-linked immunosorbent assay method. The kisspeptin and EMAP-II expression and secretion levels in the DLD-1 and HT-29 colon cancer cell lines were examined by quantitative real-time polymerase chain reaction, Western analysis and enzyme-linked immunosorbent assay, whereas lymphocyte viability was assessed by flow cytometry. The effect of kisspeptin on the viability of colon cancer cells was examined by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide]. Exogenous, synthetic and naturally produced, kisspeptin induces through the G-protein-coupled receptor 54 (GPR54; also known as the kisspeptin receptor) the EMAP-II expression and secretion in colon cancer cell lines, inducing in vitro lymphocyte apoptosis, as verified by the use of an anti-EMAP-II antibody. These results were reversed with the use of kisspeptin inhibitors and by kisspeptin-silencing experiments. Tumor kisspeptin expression was associated with the tumor EMAP-II expression (p < 0.001). Elevated kisspeptin and EMAP-II expression in colon cancer tissues was associated with lack of metastases (p < 0.001) in colon cancer patients. These data indicate the antimetastatic effect of tumor-elevated kisspeptin in colon cancer patients that may be mediated by the effect of kisspeptin on EMAP-II expression in colon cancer tumors in patients with normal serum EMAP-II levels. These findings provide new insight into the role of kisspeptin in the context of metastases in colon cancer patients.

Stathaki, Martha; Armakolas, Athanasios; Dimakakos, Andreas; Kaklamanis, Loukas; Vlachos, Ioannis; Konstantoulakis, Manoussos M; Zografos, George; Koutsilieris, Michael

2014-01-01

68

Kisspeptin effect on endothelial monocyte activating polypeptide II (EMAP-II)-associated lymphocyte cell death and metastases in colorectal cancer patients.  

PubMed

Kisspeptin is an antimetastatic agent in some cancers that has also been associated with lymphoid cell apoptosis, a phenomenon favoring metastases. Our aim was to determine the association of kisspeptin with lymphocyte apoptosis and the presence of metastases in colorectal cancer patients. Blood was drawn from 69 colon cancer patients and 20 healthy volunteers. Tissue specimens from healthy and pathological tissue were immunohistochemically analyzed for kisspeptin and endothelial monocyte activating polypeptide II (EMAP-II) expression. Blood EMAP-II and soluble Fas ligand (sFasL) levels were examined by an enzyme-linked immunosorbent assay method. The kisspeptin and EMAP-II expression and secretion levels in the DLD-1 and HT-29 colon cancer cell lines were examined by quantitative real-time polymerase chain reaction, Western analysis and enzyme-linked immunosorbent assay, whereas lymphocyte viability was assessed by flow cytometry. The effect of kisspeptin on the viability of colon cancer cells was examined by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide]. Exogenous, synthetic and naturally produced, kisspeptin induces through the G-protein-coupled receptor 54 (GPR54; also known as the kisspeptin receptor) the EMAP-II expression and secretion in colon cancer cell lines, inducing in vitro lymphocyte apoptosis, as verified by the use of an anti-EMAP-II antibody. These results were reversed with the use of kisspeptin inhibitors and by kisspeptin-silencing experiments. Tumor kisspeptin expression was associated with the tumor EMAP-II expression (p < 0.001). Elevated kisspeptin and EMAP-II expression in colon cancer tissues was associated with lack of metastases (p < 0.001) in colon cancer patients. These data indicate the antimetastatic effect of tumor-elevated kisspeptin in colon cancer patients that may be mediated by the effect of kisspeptin on EMAP-II expression in colon cancer tumors in patients with normal serum EMAP-II levels. These findings provide new insight into the role of kisspeptin in the context of metastases in colon cancer patients. PMID:24395571

Stathaki, Martha; Armakolas, Athanasios; Dimakakos, Andreas; Kaklamanis, Loukas; Vlachos, Ioannis; Konstantoulakis, Manoussos M; Zografos, George; Koutsilieris, Michael

2014-01-01

69

Peripheral type benzodiazepine receptor in T lymphocyte rich preparation  

Microsoft Academic Search

Some types of mood disorders and drugs are suggested to affect peripheral type benzodiazepine receptors (PBR), but their mechanisms are unclear. The isolation of pure lymphocytes is requisite for the investigation of the function of PBR on lymphocytes, since platelets and monocytes also have many PBR. The objective of this study was to establish a method of binding assay for

Shigeru Maeda; Takuya Miyawaki; Tohru Nakanishi; Masaharu Takigawa; Masahiko Shimada

1998-01-01

70

Altered monocyte activation markers in Tourette's syndrome: a case-control study  

PubMed Central

Background Infections and immunological processes are likely to be involved in the pathogenesis of Tourette’s syndrome (TS). To determine possible common underlying immunological mechanisms, we focused on innate immunity and studied markers of inflammation, monocytes, and monocyte-derived cytokines. Methods In a cross-sectional study, we used current methods to determine the number of monocytes and levels of C-reactive protein (CRP) in 46 children, adolescents, and adult patients suffering from TS and in 43 healthy controls matched for age and sex. Tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), soluble CD14 (sCD14), IL1-receptor antagonist (IL1-ra), and serum neopterin were detected by immunoassays. Results We found that CRP and neopterin levels and the number of monocytes were significantly higher in TS patients than in healthy controls. Serum concentrations of TNF-alpha, sIL1-ra, and sCD14 were significantly lower in TS patients. All measured values were within normal ranges and often close to detection limits. Conclusions The present results point to a monocyte dysregulation in TS. This possible dysbalance in innate immunity could predispose to infections or autoimmune reactions.

2012-01-01

71

Cannabidiol induced a contrasting pro-apoptotic effect between freshly isolated and precultured human monocytes  

SciTech Connect

It has been documented that cannabidiol (CBD) induced apoptosis in a variety of transformed cells, including lymphocytic and monocytic leukemias. In contrast, a differential sensitivity between normal lymphocytes and monocytes to CBD-mediated apoptosis has been reported. The present study investigated the pro-apoptotic effect of CBD on human peripheral monocytes that were either freshly isolated or precultured for 72 h. CBD markedly enhanced apoptosis of freshly isolated monocytes in a time- and concentration-dependent manner, whereas precultured monocytes were insensitive. By comparison, both cells were sensitive to doxorubicin-induced apoptosis. CBD significantly diminished the cellular thiols and glutathione in freshly isolated monocytes. The apoptosis induced by CBD was abrogated in the presence of N-acetyl-{sub L}-cysteine, a precursor of glutathione. In addition, precultured monocytes contained a significantly greater level of glutathione and heme oxygenase-1 (HO-1) compared to the freshly isolated cells. The HO-1 competitive inhibitor zinc protoporphyrin partially but significantly restored the sensitivity of precultured monocytes to CBD-mediated apoptosis. Collectively, our results demonstrated a contrasting pro-apoptotic effect of CBD between precultured and freshly isolated monocytes, which was closely associated with the cellular level of glutathione and the antioxidative capability of the cells.

Wu, Hsin-Ying; Chang, An-Chi; Wang, Chia-Chi; Kuo, Fu-Hua; Lee, Chi-Ya [Department and Graduate Institute of Veterinary Medicine, School of Veterinary Medicine, National Taiwan University, Taipei, Taiwan (China); Liu, Der-Zen [Graduate Institute of Biomedical Materials and Engineering, Taipei Medical University, Taipei, Taiwan (China); Jan, Tong-Rong, E-mail: tonyjan@ntu.edu.t [Department and Graduate Institute of Veterinary Medicine, School of Veterinary Medicine, National Taiwan University, Taipei, Taiwan (China)

2010-08-01

72

Impact of Human Granulocyte and Monocyte Isolation Procedures on Functional Studies  

PubMed Central

One of the first lines of defense against infection is the activation of the innate immune system. It is becoming clear that autoimmune diseases, such as rheumatoid arthritis and Crohn's disease, may be caused by disturbed innate immunity, and relating granulocyte and monocyte functions to the patient genotype has become an important part of contemporary research. Although it is essential to move this field forward, a systematic study comparing the efficacy and suitability for functional studies of the various available protocols for the isolation of these immune cells has not been performed. Here, we compare human granulocyte functionality under three enrichment protocols: (i) Ficoll density gradient centrifugation, (ii) anti-CD15 antibody-conjugated microbeads (positive selection), and (iii) Polymorphoprep. Primary monocytes were isolated in parallel using (i) anti-CD14 magnetic microbeads, (ii) non-monocyte depletion by antibody-conjugated magnetic microbeads (negative selection), (iii) RosetteSep antibody cocktail, and (iv) the classical adherence protocol. The best results in terms of purity and cell functionality were obtained with positive selection by magnetic microbeads for both human granulocytes and monocytes. Whereas phagocytosis of Escherichia coli bacteria was identical in all isolation procedures tested, the granulocyte respiratory burst was higher in positively selected cells. In addition, different granulocyte enrichment procedures affect cell surface receptor expression to different extents. In toto, we propose that positive selection of granulocytes and monocytes be adopted as the procedure of choice for studies of human granulocyte and monocyte functions but caution investigators to be aware of possible alterations in cell phenotypes with different isolation procedures.

Zhou, Lu; Somasundaram, Rajesh; Nederhof, Rosa F.; Dijkstra, Gerard; Faber, Klaas Nico; Peppelenbosch, Maikel P.

2012-01-01

73

Peripheral blood lymphocyte/monocyte ratio at the time of first relapse predicts outcome for patients with relapsed or primary refractory diffuse large B-cell lymphoma  

PubMed Central

Background Despite the use of modern immunochemotherapy regimens, a significant proportion of diffuse large B-cell lymphoma (DLBCL) patients will relapse. We proposed absolute lymphocyte count/absolute monocyte count ratio (ALC/AMC ratio) as a new prognostic factor in relapsed or primary refractory DLBCL. Methods We retrospectively analyzed 163 patients who have been diagnosed with relapsed or primary refractory DLBCL. The overall survival (OS) and progression-free survival (PFS) were measured from the time of first relapse. The Cox proportional hazards model was used to evaluate ALC/AMC ratio as prognostic factors for OS and PFS. Results On univariate and multivariate analysis performed with factors included in the saaIPI, early relapse, prior exposure to rituximab and autologous stem-cell transplantation (ASCT), the ALC/AMC ratio at the time of first relapse remained an independent predictor of PFS and OS (PFS: P?

2014-01-01

74

Microsatellite polymorphisms in the gene promoter of monocyte chemotactic protein-3 and analysis of the association between monocyte chemotactic protein-3 alleles and multiple sclerosis development  

Microsoft Academic Search

Monocyte chemotactic protein 3 (MCP-3) is a chemokine that attracts mononuclear cells, including monocytes and lymphocytes, the inflammatory cell types that predominate in multiple sclerosis lesions. We studied the possible association between the presence of a CA\\/GA microsatellite repeat polymorphism in the promoter\\/enhancer region of the MCP-3 gene and the occurrence of multiple sclerosis. DNA samples from 192 Swedish multiple

Pierre Fiten; Koen Vandenbroeck; Bénédicte Dubois; Els Van Coillie; Inge Nelissen; Jo Van Damme; Arturs Ligers; Jan Hillert; Magnus Andersson; Tomas Olsson; Ghislain Opdenakker

1999-01-01

75

Granulopoietic studies in acute lymphocytic leukemia of children  

Microsoft Academic Search

Summary Studies have been carried out on the levels of serum and urine colony stimulating activity (CSA) and peripheral blood and bone marrow colony forming cell numbers in children with acute lymphocytic leukemia (ALL) during various phases of their disease. These studies have suggested that serum and urine levels of colony stimulating factor are reduced during the initial or relapse

Asha Mangalik; William A. Robinson; Charlene P. Holton

1977-01-01

76

Recombinant Brugia malayi pepsin inhibitor (rBm33) induced monocyte function and absence of apoptotic cell death: An in vitro study  

PubMed Central

The effect of recombinant Brugia malayi pepsin inhibitor (rBm33) on human monocytes/macrophages has been examined using THP-1 cells. THP-1 cells stimulated with rBm33 showed enhanced levels of expression of pro-inflammatory cytokines (IL-1?, TNF-?, IL-6) and diminished levels of IL-12, iNOS and anti-inflammatory cytokine (IL-10) expression suggesting the predominant features of Th1 response. Phorbol-12-myristate-13-acetate (PMA) treated THP-1 cells stimulated with rBm33 and subsequent incubation with GFP expressing Escherichia coli (E. coli) for 2 h enhanced the uptake of E. coli. Nitric oxide (NO) levels measured in the supernatants of these cultures did not show significant changes. Apoptotic studies with Peripheral Blood Mononuclear Cells (PBMCs) from normal individuals stimulated with rBm33 did not induce apoptosis of monocytes or lymphocytes. These observations suggest that rBm33 stimulates macrophages to induce Th1 response and does not promote apoptosis.

Sreenivas, Kirthika; Vijayan, Kamalakannan; Babu, Subash; Narayanan, Rangarajan Badri

2012-01-01

77

Mitogenic signal transduction in T lymphocytes in microgravity  

NASA Technical Reports Server (NTRS)

The activation by concanavalin A Con A of human peripheral blood lymphocytes (PBLs) in the presence of monocytes as accessory cells was investigated in cultures exposed to microgravity conditions in Spacelab. Activation of T cells was measured as incorporation of [3H]thymidine into DNA, secretion of interleukin-2 (IL-2), and interferon-gamma, and expression of IL-2 receptors. Whereas, as discovered in earlier experiments, the activation of resuspended T cells is strongly inhibited, activation of cells attached to microcarrier beads is more than doubled in microgravity. The results suggest that the depression of the activation in resuspended cells may be attributed to a malfunction of monocytes acting as accessory cells. In fact, although the ultrastructure of resuspended monocytes is not altered in microgravity, the secretion of IL-1 is strongly inhibited. Our data suggest that (1) IL-2 is produced independently of IL-1, (2) IL-1 production is triggered only when monocytes (and lymphocytes?) adhere to microcarriers, (3) the expression of IL-2 receptors depends on IL-1, and (4) provided sufficient IL-1 is available, activation is enhanced in microgravity. Finally, cultures of resuspended PBLs and monocytes in microgravity constitute a complete and natural system in which monocytes are not operational. This may be useful for studies of the role of accessory cells and cell-cell interactions in T lymphocyte activation.

Cogoli, A.; Bechler, B.; Cogoli-Greuter, M.; Criswell, S. B.; Joller, H.; Joller, P.; Hunzinger, E.; Muller, O.

1993-01-01

78

Angiogenic Activity is Defective in Monocytes from Patients with Alopecia Universalis  

Microsoft Academic Search

Monocyte\\/macrophages are important components of cell-mediated immune responses in presentation of antigen, as regulators of lymphocyte function, and as sources of cytokines that modulate functions of cells other than those of the immune system. Their role in the pathogenesis of alopecia areata (AA) and universalis (AU) has not been explored. This study is an investigation of the function of peripheral

Alexandra Skoutelis; Ruth K. Freinkel; Daniel S. Kaufman; S. Joseph Leibovich

1990-01-01

79

Studies of Lymphocyte Growth and Differentiation. Progress Report, April 15, 1974--April 1, 1975.  

National Technical Information Service (NTIS)

Progress is reported on studies of growth in cultured lymphocytes in which it was demonstrated that ribonuclear protein maturation in lymphocyte nucleoli depends on the interaction between nascent RNA and proteins and that phytohemagglutinin (PHA) can dir...

A. D. Rubin

1975-01-01

80

A New Prognostic Score for Elderly Patients with Diffuse Large B-Cell Lymphoma Treated with R-CHOP: The Prognostic Role of Blood Monocyte and Lymphocyte Counts Is Absent  

PubMed Central

Background Absolute lymphocyte count (ALC) and absolute monocyte count (AMC) have been documented as independent predictors of survival in patients with newly diagnosed Diffuse Large B-cell Lymphoma (DLBCL). Analysis of the prognostic impact of ALC and AMC in the context of International Prognostic Index (IPI) and other significant variables in elderly population treated in the R-CHOP regime has not been carried out yet. Methodology/Principal Findings In this retrospective study, a cohort of 443 newly diagnosed DLBCL patients with age ?60 was analyzed. All patients were treated with the R-CHOP therapy. An extensive statistical analysis was performed to identify risk factors of 3-year overall survival (OS). In multivariate analysis, only three predictors proved significant: Eastern Cooperative Oncology Group performance status (ECOG), age and bulky disease presence. These predictors were dichotomized (ECOG ?1, age ?70, bulk ?7.5) to create a novel four-level score. This score predicted 3-year OS of 94.0%, 77.4%, 62.7% and 35.4% in the low-, low-intermediate, high-intermediate and high-risk groups, respectively (P<0.001). Further, a three-level score was tested which stratifies the population better (3-year OS: 91.9%, 67.2%, 36.2% in the low, intermediate and high-risk groups, respectively) but is more difficult to interpret. Both the 3- and 4-level scores were compared to standard scoring systems and, in our population, were shown to be superior in terms of patients risk stratification with respect to 3-year OS prediction. The results were successfully validated on an independent cohort of 162 patients of similar group characteristics. Conclusions The prognostic role of baseline ALC, AMC or their ratio (LMR) was not confirmed in the multivariate context in elderly population with DLBCL treated with R-CHOP. The newly proposed age-specific index stratifies the elderly population into risk groups more precisely than the conventional IPI and its existing variants.

Prochazka, Vit; Pytlik, Robert; Janikova, Andrea; Belada, David; Salek, David; Papajik, Tomas; Campr, Vit; Furst, Tomas; Furstova, Jana; Trneny, Marek

2014-01-01

81

Caspase 1 Involvement in Human Monocyte Lysis Induced by Actinobacillus actinomycetemcomitans Leukotoxin  

PubMed Central

Actinobacillus actinomycetemcomitans, an oral bacterium implicated in the etiology of periodontal diseases, produces a leukotoxin that selectively lyses primate neutrophils and monocytes, the major populations of defense cells in the periodontium. Though lysis requires expression of the receptor lymphocyte function-associated molecule 1 (LFA-1) on the cell surface, not all LFA-1-expressing leukocyte populations are equally susceptible to the toxin. In this study, the susceptibility of human leukocytes to leukotoxin-induced lysis is compared to their expression of LFA-1 and the activity of caspase 1. Cytolysis was determined by the activity of lactate dehydrogenase released from peripheral human leukocytes after 1-h exposure to leukotoxin. Monocytes were lysed at leukotoxin concentrations of ?5 ng/ml, while the corresponding values for neutrophils and lymphocytes were approximately 10 times greater. Similar LFA-1 expression was found in all susceptible cell populations irrespective of their degree of sensitivity to the toxin. Exposure of monocytes to leukotoxin increased their caspase 1 activity about fivefold within 10 to 20 min. Presence of the caspase 1 inhibitor Ac-YVAD-CMK significantly blocked the leukotoxin-induced lysis of monocytes only. At sublytic concentrations, leukotoxin induced no apoptotic activity in monocytes, as revealed by the lack of caspase 3 activation and DNA fragmentation. Monocytes are the most lysis-sensitive leukocytes for A. actinomycetemcomitans leukotoxin. Their lysis by this toxin depends on caspase 1 activation and proceeds through a process that differs from classical apoptosis.

Kelk, P.; Johansson, A.; Claesson, R.; Hanstrom, L.; Kalfas, S.

2003-01-01

82

STUDIES ON HUMAN PERIPHERAL BLOOD LYMPHOCYTES IN VITRO  

PubMed Central

A study of the kinetics of RNA and DNA synthesis in PWM-stimulated lymphocytes revealed that RNA synthesis preceded the onset of DNA synthesis by approximately 24 hr and that DNA synthesis and transformation was maximal between 66 to 78 hr. Histochemical and radioautographic studies on PWM stimulated cultures indicated that at 72 hr 50 to 60% of the cell population had been transformed by PWM, and that a distinct cell type bearing cytologic resemblance to the early plasma cell had emerged. The RNA sedimentation profile for newly synthesized RNA in PWM-stimulated cells showed that a large peak of 45 to 50 S material was formed after 24 and 40 hr. PWM thus produces a distinctive transformation of human peripheral blood lymphocytes.

Chessin, Lawrence N.; Borjeson, Jan; Welsh, Patricia D.; Douglas, Steven D.; Cooper, Herbert L.

1966-01-01

83

Lymphocyte colony forming units and its application to the study of radiosensitivity.  

National Technical Information Service (NTIS)

Kinetics and radiosensitivity of human lymphocytes were studied by the techniques of monolayer agar culture and liquid culture in vitro. In the experiments of lymphocyte kinetics, PHA was designated as a motogen for T lymphocyte. LPS, MEBC and BSA were ch...

X. Ma T. Wang H. Wang

1991-01-01

84

A bacterial flagellin in combination with proinflammatory cytokines activates human monocyte-derived dendritic cells to generate cytotoxic T lymphocytes having increased homing signals to cancer.  

PubMed

Flagellin, the cognate ligand for toll-like receptor 5, has potent adjuvant activity in various vaccines. However, its efficacy in generating dendritic cells (DCs) remains contentious. This study assessed how efficaciously Vibrio vulnificus FlaB (v-FlaB) could be used in generating a potent DC to induce antigen-specific cytotoxic T lymphocytes (CTLs). Mature DCs (mDCs) induced by the combination of v-FlaB/TNF?/IFN? were significantly more potent in inducing specific anticancer immune responses compared with the standard DCs that were maturated by the conventional cytokine cocktail of TNF?/IL-1?/IL-6/PGE(2). The potent mDCs produced a higher level of interleukin (IL)-12p70 and polarized naive CD4(+) T cells more towards Th1-type cells, markedly increased antigen-specific CD8(+) T-cell number and significantly enhanced the induction of lytic enzymes in antigen-specific CD8(+) CTLs and sensitized CD3(+) T cells to produce higher number of interferon (IFN)?-secreting cells. As a result, the mDCs produced more potent antigen-specific CTLs against the MART-1 and expressed higher levels of homing receptors CCR5 and CXCR3. More importantly, the v-FlaB/TNF?/IFN?-DCs generated from melanoma patients produced strong autologous CTLs with efficient cytotoxic activities. In conclusion, v-FlaB combined with tumor necrosis factor (TNF)? and IFN? can generate potent DCs which produce functionally active CTLs and that may have potential as a potent cancer vaccine. PMID:24316552

Hong, Cheol Yi; Kim, Soo Young; Lee, Hyun-Ju; Lee, Shee Eun; Lim, Sang Chul; Rhee, Joon Haeng; Lee, Je-Jung

2014-01-01

85

TRANSFORMATION OF MONOCYTES IN TISSUE CULTURE INTO MACROPHAGES, EPITHELIOID CELLS, AND MULTINUCLEATED GIANT CELLS: An Electron Microscope Study  

Microsoft Academic Search

The scqucntial transformation of chickcn monocytcs into macrophages, cpithelioid cells, and multinucleatcd giant cells in vitro was studied by electron microscopy after fixation and cmbcdment in situ. The following changes occur. In the nucleus, margination of chro- matin, cvidcnt in monocytes, decreases in later forms. Nucleoli become more complcx and nuclear pores increase in number. In cytoplasm, a progressive increase

JERRY S. SUTTON; LEON WEISS

1966-01-01

86

Prion protein induced signaling cascades in monocytes  

SciTech Connect

Prion proteins play a central role in transmission and pathogenesis of transmissible spongiform encephalopathies. The cellular prion protein (PrP{sup C}), whose physiological function remains elusive, is anchored to the surface of a variety of cell types including neurons and cells of the lymphoreticular system. In this study, we investigated the response of a mouse monocyte/macrophage cell line to exposure with PrP{sup C} fusion proteins synthesized with a human Fc-tag. PrP{sup C} fusion proteins showed an attachment to the surface of monocyte/macrophages in nanomolar concentrations. This was accompanied by an increase of cellular tyrosine phosphorylation as a result of activated signaling pathways. Detailed investigations exhibited activation of downstream pathways through a stimulation with PrP fusion proteins, which include phosphorylation of ERK{sub 1,2} and Akt kinase. Macrophages opsonize and present antigenic structures, contact lymphocytes, and deliver cytokines. The findings reported here may become the basis of understanding the molecular function of PrP{sup C} in monocytes and macrophages.

Krebs, Bjarne [Center for Neuropathology and Prion Research, Ludwig-Maximilians-University Munich, Muenchen (Germany); Dorner-Ciossek, Cornelia [CNS Research III, Boehringer Ingelheim Pharma GmbH and Co KG, Biberach/Riss (Germany); Schmalzbauer, Ruediger [Center for Neuropathology and Prion Research, Ludwig-Maximilians-University Munich, Munich (Germany); Vassallo, Neville [Department of Physiology and Biochemistry, University of Malta, Msida (Malta); Herms, Jochen [Center for Neuropathology and Prion Research, Ludwig-Maximilians-University Munich, Munich (Germany); Kretzschmar, Hans A. [Center for Neuropathology and Prion Research, Ludwig-Maximilians-University Munich, Munich (Germany)]. E-mail: Hans.Kretzschmar@med.uni-muenchen.de

2006-02-03

87

Prion protein induced signaling cascades in monocytes.  

PubMed

Prion proteins play a central role in transmission and pathogenesis of transmissible spongiform encephalopathies. The cellular prion protein (PrP(C)), whose physiological function remains elusive, is anchored to the surface of a variety of cell types including neurons and cells of the lymphoreticular system. In this study, we investigated the response of a mouse monocyte/macrophage cell line to exposure with PrP(C) fusion proteins synthesized with a human Fc-tag. PrP(C) fusion proteins showed an attachment to the surface of monocyte/macrophages in nanomolar concentrations. This was accompanied by an increase of cellular tyrosine phosphorylation as a result of activated signaling pathways. Detailed investigations exhibited activation of downstream pathways through a stimulation with PrP fusion proteins, which include phosphorylation of ERK(1,2) and Akt kinase. Macrophages opsonize and present antigenic structures, contact lymphocytes, and deliver cytokines. The findings reported here may become the basis of understanding the molecular function of PrP(C) in monocytes and macrophages. PMID:16343423

Krebs, Bjarne; Dorner-Ciossek, Cornelia; Schmalzbauer, Rüdiger; Vassallo, Neville; Herms, Jochen; Kretzschmar, Hans A

2006-02-01

88

Hyperketonemia increases monocyte adhesion to endothelial cells and is mediated by LFA-1 expression in monocytes and ICAM-1 expression in endothelial cells.  

PubMed

Frequent episodes of hyperketonemia are associated with a higher incidence of vascular disease. The objective of this study was to examine the hypothesis that hyperketonemia increases monocyte-endothelial cell (EC) adhesion and the development of vascular disease in diabetes. Human U937 and THP-1 monocyte cell lines and human umbilical vein endothelial cells (HUVECs) were cultured with acetoacetate (AA) (0-10 mM) or ?-hydroxybutyrate (BHB) (0-10 mM) for 24 h prior to evaluating adhesion and adhesion molecule expression. The results demonstrate a significant (P < 0.01) increase in both U937 and THP-1 adhesion to HUVEC monolayers treated with 4 mM AA compared with control. Equal concentrations of BHB resulted in similar increases in monocyte-EC adhesion. Similarly, treatments of AA or BHB to isolated monocytes from human blood also show increases in adhesion to endothelial cells. intercellular adhesion molecule-1 (ICAM-1) was significantly increased on the surface of HUVECs and an increase in total protein expression with AA treatment compared with control. The expression level of lymphocyte function-associated antigen-1 (LFA-1) was increased in monocytes treated with AA, and LFA-1 affinity was altered from low to high affinity following treatment with both AA and BHB. Monocyte adhesion could be blocked when cells were preincubated with an antibody to ICAM-1 or LFA-1. Results also show a significant increase in IL-8 and MCP-1 secretion in monocytes and HUVECs treated with 0-10 mM AA. These results suggest that hyperketonemia can induce monocyte adhesion to endothelial cells and that it is mediated via increased ICAM-1 expression in endothelial cells and increased expression and affinity of LFA-1 in monocytes. PMID:21540444

Rains, Justin L; Jain, Sushil K

2011-08-01

89

Biocompatibility of implants: lymphocyte\\/macrophage interactions  

Microsoft Academic Search

The monocyte-derived macrophage is recognized as a critical determinant in biocompatibility, but its appearance in the chronic\\u000a inflammatory phase is accompanied by the presence of lymphocytes, which have been much less studied in this regard. Here,\\u000a we first present an overview of the physiologic continuum comprising host reactions to the surgical implantation of biomaterial.\\u000a Secondly, we describe our collective research

James M. Anderson; Amy K. McNally

2011-01-01

90

Specific Role of Each Human Leukocyte Type in Viral Infections I. Monocyte as Host Cell for Vesicular Stomatitis Virus Replication In Vitro  

PubMed Central

Each major leukocyte type of the peripheral blood of healthy donors was studied in vitro for its ability to support vesicular stomatitis virus (VSV) replication. Purified cultures of each white blood cell type were prepared by the selective adsorption and elution of cells from silicone-treated glass beads. It was found that monocytes and macrophages (derived from the rapid transformation of monocytes in vitro) were the principal host cells for VSV replication. Interferon added to mixed leukocyte cultures, prior to virus inoculation, reduced virus yields and prevented destruction of macrophages. Cultures of small lymphocytes, containing no detectable monocytes or macrophages, produced amounts of virus equivalent to 1% of that produced in leukocyte cultures which contained 7% monocytes. Small lymphocytes did not undergo demonstrable cytopathic alterations in virus-infected cultures. VSV neither replicated nor produced cytopathic effects in polymorphonuclear leukocytes. Images

Edelman, Robert; Wheelock, E. Frederick

1967-01-01

91

Ultrastructural and Immunocytochemical Study of the Uptake and Distribution of Bacterial Lipopolysaccharide in Human Monocytes.  

National Technical Information Service (NTIS)

Interaction of bacterial lipopolysaccharide (LPS) with monocytes stimulates production of a variety of mediators that are involved in the pathogenesis of septic shock and wound repair. The mechanisms of LPS uptake and intracellular distribution of LPS in ...

Y. H. Kang R. S. Dwivedi C. H. Lee

1990-01-01

92

Pathology Case Study: Chronic Lymphocytic Leukemia (CLL) and Malignant Melanoma  

NSDL National Science Digital Library

The Department of Pathology at the University of Pittsburgh Medical Center has compiled a wide range of pathology case studies to aid students and instructors in the medical/health science field. This specific case documents the condition of a 74 year-old man suspected of having either chronic lymphocytic leukemia or malignant melanoma. The patientâÂÂs history, images from his bone marrow biopsy, and final diagnosis are provided in this case for your review. Students will find this resource especially helpful, as it provides experience with patient history, lab results, and diagnostics.

Callahan, Debra L.

2009-09-01

93

Monocyte matrix metalloproteinase production in Type 2 diabetes and controls – a cross sectional study  

Microsoft Academic Search

Background  Coronary plaque rupture may result from localised over expression of matrix metalloproteinases (MMPs) within the plaque by\\u000a infiltrating monocyte – macrophages. As MMP expression can be promoted by the modified lipoproteins, oxidative stress and\\u000a hyperglycaemia that characterises Type 2 diabetes, we hypothesised that peripheral monocytes in these patients, exposed to\\u000a these factors in vivo, would demonstrate increased MMP production compared

Mark D Baugh; Jelena Gavrilovic; Isabel R Davies; David A Hughes; Mike J Sampson

2003-01-01

94

Effect of salmonella-infected human monocytes on natural killer cell cytotoxicity. In vitro studies  

Microsoft Academic Search

Various chemicals, including some bacteria-derived components, modulate natural killer cell (NKC) activity. We have analyzed the effect of wild-type Ty2 and of mutant strain TYT1231 Salmonella typhi-infected monocytes (U937 cells and human autologous monocytes) on NKC cytotoxicity of peripheral blood mononuclear cell (PBMC) and highly purified NKC (HPNKC; CD16+\\/56+>95%; the rest corresponding to CD3+ T-cells).PBMC's co-culture with either S. typhi

Luz Blanco; Javier Puente; Carolina Carrasco; Dante Miranda; Marion E Wolf; Aron D Mosnaim

2001-01-01

95

Inhibition of macrophage inflammatory protein-1 alpha expression by IL-10. Differential sensitivities in human blood monocytes and alveolar macrophages.  

PubMed

IL-10 is a pleiotropic cytokine produced by monocytes and T cells that has potent inhibitory effects on monocyte/macrophage function. Because monocytes and macrophages are capable of releasing the C-C chemokine, macrophage inflammatory protein-1 alpha (MIP-1 alpha), which is a potent chemoattractant for activated T cells, we studied the effects of IL-10 on the expression of MIP-1 alpha in these cells. Low levels of MIP-1 alpha were detectable in resting monocytes and macrophages. Both LPS (1 micrograms/ml) and IL-1 beta (10 ng/ml) induced the expression of MIP-1 alpha mRNA and the release of MIP-1 alpha protein from these cells. The addition of exogenous human rIL-10 inhibited induced MIP-1 alpha mRNA expression as well as the release of MIP-1 alpha protein measured after 24 h. This inhibition was significantly higher in monocytes compared with alveolar macrophages. In monocytes, IL-10-induced inhibition of MIP-1 alpha was only partially accounted for by alterations in mRNA stability and was dependent on de novo protein synthesis. In the presence of an anti-human IL-10-neutralizing Ab, the release of MIP-1 alpha induced by LPS and IL-1 beta was further enhanced in monocytes but unchanged in alveolar macrophages. MIP-1 alpha mRNA was also increased in monocytes. There was no detectable release of IL-10 from alveolar macrophages after LPS or IL-1 beta in contrast to modest amounts released from monocytes. Thus, IL-10 is an inhibitor of the induced transcription of MIP-1 alpha mRNA and of the release of MIP-1 alpha protein, with a greater effect on monocytes as compared with alveolar macrophages. IL-10 may indirectly regulate effects on cells such as activated T lymphocytes partly through the inhibition of MIP-1 alpha expression from monocytes and macrophages. PMID:7594602

Berkman, N; John, M; Roesems, G; Jose, P J; Barnes, P J; Chung, K F

1995-11-01

96

Interactions between comorbidity and treatment of chronic lymphocytic leukemia: results of German Chronic Lymphocytic Leukemia Study Group trials  

PubMed Central

This study investigated the impact of comorbidity in 555 patients with chronic lymphocytic leukemia enrolled in two trials of the German Chronic Lymphocytic Leukemia Study Group on first-line treatment with fludarabine plus cyclophosphamide, fludarabine, or chlorambucil. Patients with two or more comorbidities and patients with less than two comorbidities differed in overall survival (71.7 versus 90.2 months; P<0.001) and progression-free survival (21.0 versus 31.5 months; P<0.01). After adjustment for other prognostic factors and treatment, comorbidity maintained its independent prognostic value in a multivariate Cox regression analysis. Chronic lymphocytic leukemia was the major cause of death in patients with two or more comorbidities. Disease control in patients with two or more comorbidities was better with fludarabine plus cyclophosphamide than with fludarabine treatment, but not with fludarabine compared to chlorambucil treatment. These results give insight into interactions between comorbidity and therapy of chronic lymphocytic leukemia and suggest that durable control of the hematologic disease is most critical to improve overall outcome of patients with increased comorbidity. The registration numbers of the trials reported are NCT00276848 and NCT00262795.

Goede, Valentin; Cramer, Paula; Busch, Raymonde; Bergmann, Manuela; Stauch, Martina; Hopfinger, Georg; Stilgenbauer, Stephan; Dohner, Hartmut; Westermann, Anne; Wendtner, Clemens M.; Eichhorst, Barbara; Hallek, Michael

2014-01-01

97

Interactions between comorbidity and treatment of chronic lymphocytic leukemia: results of German Chronic Lymphocytic Leukemia Study Group trials.  

PubMed

This study investigated the impact of comorbidity in 555 patients with chronic lymphocytic leukemia enrolled in two trials of the German Chronic Lymphocytic Leukemia Study Group on first-line treatment with fludarabine plus cyclophosphamide, fludarabine, or chlorambucil. Patients with two or more comorbidities and patients with less than two comorbidities differed in overall survival (71.7 versus 90.2 months; P<0.001) and progression-free survival (21.0 versus 31.5 months; P<0.01). After adjustment for other prognostic factors and treatment, comorbidity maintained its independent prognostic value in a multivariate Cox regression analysis. Chronic lymphocytic leukemia was the major cause of death in patients with two or more comorbidities. Disease control in patients with two or more comorbidities was better with fludarabine plus cyclophosphamide than with fludarabine treatment, but not with fludarabine compared to chlorambucil treatment. These results give insight into interactions between comorbidity and therapy of chronic lymphocytic leukemia and suggest that durable control of the hematologic disease is most critical to improve overall outcome of patients with increased comorbidity. The registration numbers of the trials reported are NCT00276848 and NCT00262795. PMID:24584349

Goede, Valentin; Cramer, Paula; Busch, Raymonde; Bergmann, Manuela; Stauch, Martina; Hopfinger, Georg; Stilgenbauer, Stephan; Döhner, Hartmut; Westermann, Anne; Wendtner, Clemens M; Eichhorst, Barbara; Hallek, Michael

2014-06-01

98

Alteration of monocytic cell oxidative burst caused by methacrylic monomers present in dental materials: a chemiluminescence study.  

PubMed

Methacrylates are present in dental composite resins used in clinical practice. Methacrylates are photo-polymerized, but this reaction is never complete, so release of uncured monomers in the periapical tissues and in biological fluids may happen and, potentially, alter the repair of pulpal and of periapical lesions by interfering with local phagocytes. The aim of this study was the evaluation of the functional activity of the monocyte-macrophage system after incubation with methacrylic monomers. The oxidative burst of two cellular systems was analysed using the chemiluminescence technique. Data were collected and statistically analysed. Monomers were found to reduce the in vitro oxidative burst of phagocytes independently from their cytotoxicity. These findings demand further evaluation of the effects of oxidative burst alteration in monocyte-macrophage function and may prompt the inclusion of the described chemiluminescence test in biocompatibility preliminary studies of dental materials. PMID:16645960

Nocca, Giuseppina; De Sole, Pasquale; Gambarini, Gianluca; De Palma, Francesco; Parziale, Vito; Giardina, Bruno; Lupi, Alessandro

2006-01-01

99

A study of porcine lymphocyte populations. II. Characterization of porcine lymphocyte populations.  

PubMed

The percentage of E rosette forming cells amounted to 26% of the blood lymphocytes and 34% of the spleen cells in German Landrace pigs. 10% of the live lymphocytes in the peripheral blood and 22% of the spleen cells were EAC rosette forming cells. The number of E rosettes could be increased by treatment of sheep erythrocytes with neuraminidase. The number of lymphoid cells reacting with protein A in the peripheral blood and in the spleen of pigs correlated well with the number of EAC rosette forming cells. The mitogens phytohemagglutinin (PHA), concanavalin A (Con A) and pokeweed mitogen (PWM) are potent stimulators of pig lymphoid cells. The mitogenic stimulation of pig lymphocytes could not be influenced significantly by the removal of phagocytic cells. By neuraminidase treatment the mitogen induced stimulation rate was decreased. For the mitogenic stimulation of porcine lymphoid cells in the presence of PHA, Con A and PWM T cells were required. Bacterial lipopolysaccharides (LPS) stimulated only B cells to a small degree. PMID:15615057

Buschmann, H; Pawlas, S

1980-08-01

100

Monocytic differentiation induced by 1,25 dihydroxyvitamin D3 in myeloid cells: an ultrastructural immunocytochemical study.  

PubMed

We have studied, by ultrastructural morphology and immunocytochemistry, the alterations that occur in cells from the HL60 leukaemia cell line and from patients with CGL following incubation in vitro with 1,25(OH)2D3 for 2-5 days. The main morphological changes observed were in the nuclear shape, the development of autophagic vacuoles and the appearance of a population of small granules in the cytoplasm. These changes were associated with a significant reduction in MPO activity and increased expression of membrane antigens detected by the monocyte-specific McAb FMC17 and FMC32, as shown by the IGM at EM level, and a decrease in granulocyte-specific antigens demonstrated by the McAb FMC10. These observations suggest that promyelocytes and myelocytes could transform into monocyte-like cells and that this remodelling of cells was associated with autophagic digestion of cellular structures. PMID:3857411

Polli, N; O'Brien, M; Tavares de Castro, J; Rodriguez, B; McCarthy, D; Catovsky, D

1985-01-01

101

Abnormal bronchoalveolar lavage in asymptomatic dairy farmers. Study of lymphocytes.  

PubMed

Bronchoalveolar lavage (BAL) was performed on 24 asymptomatic dairy farmers. Thirteen had serum precipitins to Micropolyspora faeni (MF) antigens (Group 1), and 11 were seronegative control subjects (Group 2). All were nonsmokers and had no history of previous lung disease. Thirteen of 24 subjects (9 in Group 1 and 4 in Group 2) had a high percentage of lymphocytes (greater than or equal to 20%) in their BAL. The T-lymphocyte subpopulations as estimated by OKT3, OKT4, and OKT8 monoclonal antibody reactivity were measured in peripheral blood lymphocytes; OKT3 = 58.5 +/- 15.6% for Group 1, and 58.5 +/- 8.7% for Group 2; OKT4 = 40.6 +/- 10.7% and 39.9 +/- 10.0%; OKT8 = 21.5 +/- 10.6% and 22.4 +/- 8.0%, respectively (p = NS). These lymphocyte characteristics were also similar when subjects with a high percentage of lymphocytes in BAL were compared to those with a normal percentage. Specific (MF-coated) chicken erythrocyte lymphocytotoxicity (Group 1, 45.2 +/- 29.5%, Group 2, 49.2 +/- 23.4%), and nonspecific lymphocytotoxicity (Group 1, 43.9 +/- 28.6%, Group 2, 37.9 +/- 18.0%) were also similar. We conclude that a large number of asymptomatic dairy farmers have an increased percentage of lymphocytes in their BAL ("alveolitis") and that peripheral blood lymphocytes in these subjects have normal subpopulations, as assessed by monoclonal antibodies, and normal lymphocytotoxicity. PMID:6508002

Cormier, Y; Bélanger, J; Beaudoin, J; Laviolette, M; Beaudoin, R; Hebert, J

1984-12-01

102

Changes in Monocyte Functions of Astronauts  

NASA Technical Reports Server (NTRS)

Monocyte cell numbers and functions, including phagocytosis, oxidative burst capacity, and degranulation and expression of related surface molecules, were studied in blood specimens from 25 astronauts and 9 healthy control subjects. Blood samples were obtained 10 days before a space flight, 3 hours after landing and 3 days after landing. The number of monocytes in astronauts did not change significantly among the three sample collection periods. Following space flight, the monocytes ability to phagocytize Escherichia coli, to exhibit an oxidative burst, and to degranulate was reduced as compared to monocytes from control subjects. These alterations in monocyte functions after space flight correlated with alterations in the expression of CD32 and CD64.

Kaur, I.; Simons, E.; Castro, V.; Ott, C. Mark; Pierson, Duane L.

2004-01-01

103

Cytogenetic studies of blood lymphocytes from cosmonauts after long-term space flights on MIR station  

Microsoft Academic Search

Long-term space missions may increase risks of unfavorable consequences for cosmonauts as a result of radiation effects. This paper presents results of a study of cytogenetic damage in cosmonauts' peripheral blood lymphocytes induced by space radiation. Cultivation of lymphocytes and analysis of chromosomal aberrations were made according to generally accepted methods. It is shown that the yields of dicentrics and

B. Fedorenko; S. Druzhinin; L. Yudaeva; V. Petrov; Yu. Akatov; G. Snigiryova; N. Novitskaya; V. Shevchenko; A. Rubanovich

2001-01-01

104

Tissue Culture Studies of Human Lymphocyte in Infectious Mononucleosis.  

National Technical Information Service (NTIS)

The site of production for the heterophile antibody in patients with infectious mononucleosis is unknown. Atypical lymphocytes from patients with infectious mononucleosis were grown in tissue culture in an attempt to demonstrate heterophile antibody produ...

R. A. Gams C. A. Coltman

1968-01-01

105

Ultrastructural studies of a lysosomal enzyme during lymphocyte activation.  

PubMed Central

A post-embedding immunogold technique has been used for the ultrastructural localization of a lysosomal enzyme, beta-glucuronidase, in resting and activated T- and B-lymphocytes. The results presented here show that mitogen-induced stimulation of T- and B-cells was associated with an increase in the amount of enzyme in the Golgi complex and rough endoplasmic reticulum, organelles which were rarely present in the resting lymphocytes. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4

Bou-Gharios, G.; Moss, J.; Abraham, D.; Partridge, T.; Olsen, I.

1988-01-01

106

Clonal Studies of CD3 - Lymphoproliferative Disease of Granular Lymphocytes  

Microsoft Academic Search

HE LYMPHOPROLIFERATIVE disease of granular T lymphocytes (LDGL) results from a chronic prolifer- ation of large granular lymphocytes (LGLs) that may have either a CD3+ or CD3- phenotype.'-' It is conceivable that LDGL could encompass both neoplastic or reactive condi- tion~.',~ Most patients with a CD3+ LGL disorder have clonal rearrangements of the T-cell receptor (TCR) \\/3 gene, sup- porting

Richard Nash; Peter McSweeney; Renato Zambello; Gianpietro Semenzato; Thomas P. Loughran

1993-01-01

107

Assessment of monocytic component in acute myelomonocytic and monocytic\\/monoblastic leukemias by a chemiluminescent assay  

Microsoft Academic Search

Introduction: Classically, the monocytic component of acute myelomonocytic (FAB-M4) and acute monocytic\\/monoblastic (FAB-M5) leukemias is demonstrated by nonspecific esterase positivity in cytochemical stainings. We have previously demonstrated that non- specific esterases from normal monocytes can be determined by a chemiluminescent method. In the present study, we investigated whether this assay can also determine the monocytic component of FAB-M4 and FAB-M5

Luiz M da Fonseca; Iguatemy L Brunetti; Ana Campa; Luiz H Catalani; Rodrigo T Calado; Roberto P Falcăo

2003-01-01

108

Lymphocyte migration into three-dimensional collagen matrices: a quantitative study  

PubMed Central

Lymphocytes have been plated onto the surface of three-dimensional gels of native collagen fibers, and their distribution throughout the three- dimensional collagen matrix has been determined in a quantitative fashion at various times thereafter. Information regarding the total number of applied cells may be obtained by this means. Lymphocyte penetration into the collagen gel does not appear to involve the expression of collagenolytic activity, nor does it require the presence of serum. Analysis of the kinetics of lymphocyte penetration into the gel matrix indicates that lymphocytes are migrating in a "random-walk" fashion. Our objective has been to establish a model system for studying the cell-matrix and cell-cell interactions which influence the pattern of lymphocyte recirculation in vivo and the results presented here are discussed in this context.

1983-01-01

109

Monocyte Function in Psoriasis  

Microsoft Academic Search

Monocytes derived from the peripheral blood of psoriatic patients demonstrated a significantly higher phagocytic capacity (36 to 40%) for both 125I-labeled Shigella flexneri and 125I-labeled Staphylococcus albus compared with monocytes from healthy subjects. Monocytes from psoriatic patients showed a 2-to-4fold increase in bactericidal capacity against S. albus when compared with normal monocytes. However, the bactericidal capacity of monocytes from diphylline-treated

Menashe Bar-Eli; Ruth Gallily; Haim A. Cohen; Asher Wahba

1979-01-01

110

Study of splenic irradiation in chronic lymphocytic leukemia  

SciTech Connect

A retrospective study was performed to assess the effect of splenic irradiation (SI) on splenomegaly, splenic pain, anemia, and thrombocytopenia in patients with chronic lymphocytic leukemia. Twenty-two patients received 32 courses of SI. Of 31 courses of SI given for splenomegaly there were 19 responders (61%). Ten courses of SI were given for splenic pain resulting in partial relief of pain in 4 courses and complete relief in 4 courses. Only 4 of 16 courses given for anemia resulted in elevations of hemoglobin of 2 g/dL or more. Of the 14 courses of SI given for thrombocytopenia there were only 2 responses with platelet counts decreasing further in another 9 courses. The median duration of response was 14 months (range: 3-116 months). There was no dose-response relationship detected for SI in CLL. Treatment related toxicity was hematologic and secondary to leucopenia and thrombocytopenia. We recommend the use of small fraction sizes of 25 cGy to 50 cGy and close monitoring of hematological parameters. Splenic irradiation effectively palliates splenomegaly and reduces spleen size in CLL. It was of limited value in correcting anemia and thrombocytopenia in this patient population.

Guiney, M.J.; Liew, K.H.; Quong, G.G.; Cooper, I.A.

1989-01-01

111

Effects of raloxifene treatment on the phenotype of blood monocytes.  

PubMed

Raloxifene (RLX), a selective oestrogen receptor modulator, has oestrogen-agonist effects on bone, lipoproteins, and homocysteine and oestrogen-antagonist activity in the breast and uterus, positioning it as a potential drug for long-term prevention of coronary heart disease in postmenopausal women. To further evaluate its influence on cardiovascular risk factors, we studied the effects of 60 mg/day RLX on serum lipid levels, inflammatory (high-sensitivity C-reactive protein, and coagulation (fibrinogen) markers, monocytes, and fibrinolysis in 15 healthy postmenopausal women. Markers were measured at baseline, after 1 month without treatment, and after 3 months of treatment. Fibrinolysis was evaluated using the euglobulin clot lysis time (ECLT) determined with a new semiautomatic optical method. Monocyte phenotype was determined by measurement of the expression of the antigens CD14, HLA-DR, and CD62-L using flow cytometry. After 3 months of RLX treatment, we observed a decrease in total cholesterol (p = 0.002), in low-density lipoprotein cholesterol (p <0.001), and in lipoprotein A (p = 0.01). Fibrinogen (p = 0.002) decreased significantly, and high-sensitivity C-reactive protein had a tendency to decrease, but this did not reach statistical significance (p = 0.06). RLX treatment had no effect on ECLT (p = 0.223) or on white blood cell, lymphocyte, and total monocyte counts (p = 0.313). Monocyte expression of HLA-DR, CD14, and CD62-L was not modified by the treatment. In conclusion, we confirm that RLX has beneficial short-term effects on levels of lipids and inflammatory markers, with no effect on fibrinolysis or monocyte phenotype. PMID:20555430

Boudjeltia, Karim Zouaoui; Durez, Patrick; Oberweis, Didier; Guillaume, Michel; Remacle, Claude; Cauchie, Philippe; Vanhaeverbeek, Michel; Brohée, Dany; Ducobu, Jean; Gregoir, Catherine

2010-05-01

112

Changes in T-Cell and Monocyte Phenotypes In Vitro by Schistosoma mansoni Antigens in Cutaneous Leishmaniasis Patients  

PubMed Central

High levels of proinflammatory cytokines such as IFN-? and TNF are associated with tissue lesions in cutaneous leishmaniasis (CL). We previously demonstrated that Schistosoma mansoni antigens downmodulate the in vitro cytokine response in CL. In the current study we evaluated whether S. mansoni antigens alter monocyte and T-lymphocyte phenotypes in leishmaniasis. Peripheral blood mononuclear cells of CL patients were cultured with L. braziliensis antigen in the presence or absence of the S. mansoni antigens rSm29, rSmTSP-2- and PIII. Cells were stained with fluorochrome conjugated antibodies and analyzed by flow cytometry. The addition of rSm29 to the cultures decreased the expression of HLA-DR in nonclassical (CD14+CD16++) monocytes, while the addition of PIII diminished the expression of this molecule in classical (CD14++CD16?) and intermediate (CD14++CD16+) monocytes. The addition of PIII and rSmTSP-2 resulted in downmodulation of CD80 expression in nonclassical and CD86 expression in intermediate monocytes, respectively. These two antigens increased the expression of CTLA-4 in CD4+ T cells and they also expanded the frequency of CD4+CD25highFoxp3+ T cells. Taken together, we show that S. mansoni antigens, mainly rSmTSP-2 and PIII, are able to decrease the activation status of monocytes and also to upregulate the expression of modulatory molecules in T lymphocytes.

Bafica, Aline Michelle Barbosa; Cardoso, Luciana Santos; Oliveira, Sergio Costa; Loukas, Alex; Goes, Alfredo; Oliveira, Ricardo Riccio; Carvalho, Edgar M.; Araujo, Maria Ilma

2012-01-01

113

Facilitative glucose transporter gene expression in human lymphocytes, monocytes, and macrophages: a role for GLUT isoforms 1, 3, and 5 in the immune response and foam cell formation  

Microsoft Academic Search

Cellular glucose uptake is mediated by a family of facilitative glucose transporters (GLUT) exhibiting differences in kinetics, substrate specificity, and tissue-specific expression. GLUT isoform expression has not been comprehensively studied in human leukocytes, which participate in immune and inflammatory responses and are critical for host defense. Therefore, we studied the regulated expression of GLUT 1–5 mRNA and protein in isolated

Yuchang Fu; Lidia Maianu; Barry R Melbert; W. Timothy Garvey

2004-01-01

114

Studies of Lymphocyte Growth and Differentiation. Progress Report, September 1, 1975--July 31, 1976.  

National Technical Information Service (NTIS)

Studies were continued on ribonuclear protein synthesis and the assembly of ribosomes in resting and stimulated lymphocytes. We demonstrated the interdependency of protein synthesis and RNA synthesis in the formation and processing of nascent ribonuclear ...

A. D. Rubin

1976-01-01

115

Monocyte-mediated defense against microbial pathogens.  

PubMed

Circulating blood monocytes supply peripheral tissues with macrophage and dendritic cell (DC) precursors and, in the setting of infection, also contribute directly to immune defense against microbial pathogens. In humans and mice, monocytes are divided into two major subsets that either specifically traffic into inflamed tissues or, in the absence of overt inflammation, constitutively maintain tissue macrophage/DC populations. Inflammatory monocytes respond rapidly to microbial stimuli by secreting cytokines and antimicrobial factors, express the CCR2 chemokine receptor, and traffic to sites of microbial infection in response to monocyte chemoattractant protein (MCP)-1 (CCL2) secretion. In murine models, CCR2-mediated monocyte recruitment is essential for defense against Listeria monocytogenes, Mycobacterium tuberculosis, Toxoplasma gondii, and Cryptococcus neoformans infection, implicating inflammatory monocytes in defense against bacterial, protozoal, and fungal pathogens. Recent studies indicate that inflammatory monocyte recruitment to sites of infection is complex, involving CCR2-mediated emigration of monocytes from the bone marrow into the bloodstream, followed by trafficking into infected tissues. The in vivo mechanisms that promote chemokine secretion, monocyte differentiation and trafficking, and finally monocyte-mediated microbial killing remain active and important areas of investigation. PMID:18303997

Serbina, Natalya V; Jia, Ting; Hohl, Tobias M; Pamer, Eric G

2008-01-01

116

Monocyte-Mediated Defense Against Microbial Pathogens  

PubMed Central

Circulating blood monocytes supply peripheral tissues with macrophage and dendritic cell (DC) precursors and, in the setting of infection, also contribute directly to immune defense against microbial pathogens. In humans and mice, monocytes are divided into two major subsets that either specifically traffic into inflamed tissues or, in the absence of overt inflammation, constitutively maintain tissue macrophage/DC populations. Inflammatory monocytes respond rapidly to microbial stimuli by secreting cytokines and antimicrobial factors, express the CCR2 chemokine receptor, and traffic to sites of microbial infection in response to monocyte chemoattractant protein (MCP)-1 (CCL2) secretion. In murine models, CCR2-mediated monocyte recruitment is essential for defense against Listeria monocytogenes, Mycobacterium tuberculosis, Toxoplasma gondii, and Cryptococcus neoformans infection, implicating inflammatory monocytes in defense against bacterial, protozoal, and fungal pathogens. Recent studies indicate that inflammatory monocyte recruitment to sites of infection is complex, involving CCR2-mediated emigration of monocytes from the bone marrow into the bloodstream, followed by trafficking into infected tissues. The in vivo mechanisms that promote chemokine secretion, monocyte differentiation and trafficking, and finally monocyte-mediated microbial killing remain active and important areas of investigation.

Serbina, Natalya V.; Jia, Ting; Hohl, Tobias M.; Pamer, Eric G.

2010-01-01

117

Specificity studies on cytolytic T lymphocytes directed against murine leukemia virus-induced tumors. Analysis of monoclonal cytolytic T lymphocytes  

PubMed Central

The specificities of cloned cytolytic T lymphocytes (CTL) were studied for the analysis of CTL populations generated against murine leukemia viruses (MuLV) in H-2 congenic BALB/c (H-2d) and BALB.B (H-2b) mice. In particular, CTL generated in response to tumors induced by Gross MuLV and Friend MuLV were studied; these tumors expressed virus-induced antigens that do not cross-react and that can be distinguished from each other. The systematic study of 92 CTL clones clearly indicated that MuLV-immune CTL were highly heterogeneous with respect to both the intensities of target cell lysis that they mediated and to their specificity of recognition of MuLV-induced tumor target cells. Various categories of CTL clones were identified, ranging from CTL clones tht were tightly H-2 restricted and specific for the immunizing tumor to CTL clones that displayed no discernible patterns of specificity and that attacked a large number of different target cells. In addition, the surface markers of these cloned CTL were defined, and the best conditions for their prolonged maintenance in culture were determined. The present data indicate that future efforts in the definition of target antigens recognized by tumor-specific CTL should be performed with monoclonal lymphocytes.

1982-01-01

118

Standardized flow cytometry assay for identification of human monocytic heterogeneity and LRP1 expression in monocyte subpopulations: Decreased expression of this receptor in nonclassical monocytes.  

PubMed

In this article, we present a flow cytometry assay by which human blood monocyte subpopulations-classical (CD14(++) CD16(-) ), intermediate (CD14(++) CD16(+) ), and nonclassical (CD14(+) CD16(++) ) monocytes-can be determined. Monocytic cells were selected from CD45(+) leukocyte subsets by differential staining of the low-density lipoprotein receptor-related protein 1 (LRP1), which allows reducing the spill-over of natural killer cells and granulocytes into the CD16(+) monocyte gate. Percentages of monocyte subpopulations established by this procedure were significantly comparable with those obtained by a well-standardized flow cytometry assay based on the HLA-DR monocyte-gating strategy. We also demonstrated that LRP1 is differentially expressed at cell surface of monocyte subpopulations, being significantly lower in nonclassical monocytes than in classical and intermediate monocytes. Cell surface expression of LRP1 accounts for only 20% of the total cellular content in each monocyte subpopulation. Finally, we established the within-individual biological variation (bCV%) of circulating monocyte subpopulations in healthy donors, obtaining values of 21%, 20%, and 17% for nonclassical, intermediate, and classical monocytes, respectively. Similar values of bCV% for LRP1 measured in each monocyte subpopulation were also obtained, suggesting that its variability is mainly influenced by the intrinsic biological variation of circulating monocytes. Thus, we conclude that LRP1 can be used as a third pan-monocytic marker together with CD14 and CD16 to properly identify monocyte subpopulations. The combined determination of monocyte subpopulations and LRP1 monocytic expression may be relevant for clinical studies of inflammatory processes, with special interest in atherosclerosis and cardiovascular disease. © 2014 International Society for Advancement of Cytometry. PMID:24639232

Ferrer, Darío G; Jaldín-Fincati, Javier R; Amigone, José L; Capra, Raul H; Collino, César J; Albertini, Ricardo A; Chiabrando, Gustavo A

2014-07-01

119

The human leukemia cell line, THP1: A multifacetted model for the study of monocyte-macrophage differentiation  

Microsoft Academic Search

Summary THP-1 is a human monocytic leukemia cell line. After treatment with phorbol esters, THP-1 cells differentiate into macrophage-like cells which mimic native monocyte-derived macrophages in several respects. Compared to other human myeloid cell lines, such as HL-60, U937, KG-1, or HEL cell lines, differentiated THP-1 cells behave more like native monocyte-derived macrophages. Because of these characteristics, the THP-1 cell

J. Auwerx

1991-01-01

120

HIV-1 latency in monocytes/macrophages.  

PubMed

Human immunodeficiency virus type 1 (HIV-1) targets CD4+ T cells and cells of the monocyte/macrophage lineage. HIV pathogenesis is characterized by the depletion of T lymphocytes and by the presence of a population of cells in which latency has been established called the HIV-1 reservoir. Highly active antiretroviral therapy (HAART) has significantly improved the life of HIV-1 infected patients. However, complete eradication of HIV-1 from infected individuals is not possible without targeting latent sources of infection. HIV-1 establishes latent infection in resting CD4+ T cells and findings indicate that latency can also be established in the cells of monocyte/macrophage lineage. Monocyte/macrophage lineage includes among others, monocytes, macrophages and brain resident macrophages. These cells are relatively more resistant to apoptosis induced by HIV-1, thus are important stable hideouts of the virus. Much effort has been made in the direction of eliminating HIV-1 resting CD4+ T-cell reservoirs. However, it is impossible to achieve a cure for HIV-1 without considering these neglected latent reservoirs, the cells of monocyte/macrophage lineage. In this review we will describe our current understanding of the mechanism of latency in monocyte/macrophage lineage and how such cells can be specifically eliminated from the infected host. PMID:24759213

Kumar, Amit; Abbas, Wasim; Herbein, Georges

2014-04-01

121

HIV-1 Latency in Monocytes/Macrophages  

PubMed Central

Human immunodeficiency virus type 1 (HIV-1) targets CD4+ T cells and cells of the monocyte/macrophage lineage. HIV pathogenesis is characterized by the depletion of T lymphocytes and by the presence of a population of cells in which latency has been established called the HIV-1 reservoir. Highly active antiretroviral therapy (HAART) has significantly improved the life of HIV-1 infected patients. However, complete eradication of HIV-1 from infected individuals is not possible without targeting latent sources of infection. HIV-1 establishes latent infection in resting CD4+ T cells and findings indicate that latency can also be established in the cells of monocyte/macrophage lineage. Monocyte/macrophage lineage includes among others, monocytes, macrophages and brain resident macrophages. These cells are relatively more resistant to apoptosis induced by HIV-1, thus are important stable hideouts of the virus. Much effort has been made in the direction of eliminating HIV-1 resting CD4+ T-cell reservoirs. However, it is impossible to achieve a cure for HIV-1 without considering these neglected latent reservoirs, the cells of monocyte/macrophage lineage. In this review we will describe our current understanding of the mechanism of latency in monocyte/macrophage lineage and how such cells can be specifically eliminated from the infected host.

Kumar, Amit; Abbas, Wasim; Herbein, Georges

2014-01-01

122

Studies in chronic lymphocytic leukaemia II. Lymphocyte markers, cellular and humoral immunity and the effect of treatment.  

PubMed Central

Observations were made on 15 patients with chronic lymphocytic leukaemia, 3 with non-Hodgkin's lymphoma, and 18 healthy controls. These include characterization of lymphocytes, assessment of humoral and cell-mediated immunity and the effect of treatment. Those responding to therapy showed a disappearance of 'null' lymphocytes from the blood with improvement in clinical and haematological parameters. Their immune capacity, however, remained unchanged or continued to deteriorate.

Bazerbashi, M. B.; Chanarin, I.; Denman, A. M.

1980-01-01

123

Green fluorescent protein-transgenic mice: immune functions and their application to studies of lymphocyte development  

Microsoft Academic Search

Green fluorescent protein (GFP) transgenic (GFP+) mice express GFP in most tissues except erythrocytes and hair. Immune responses of GFP+ mouse and their application to studies of lymphocyte development were investigated. Flow cytometric analyses revealed that differentiation patterns of lymphocytes from GFP+ mice are equivalent to those from parental C57BL\\/6 mice. There was no difference in mature T-cell proliferative ability

Naoto Kawakami; Naoki Sakane; Fumiko Nishizawa; Mutsumi Iwao; So-ichiro Fukada; Kazutake Tsujikawa; Yasuhiro Kohama; Masahito Ikawa; Masaru Okabe; Hiroshi Yamamoto

2000-01-01

124

Experimental Study on Effect of Simulated Microgravity on Structural Chromosome Instability of Human Peripheral Blood Lymphocytes  

PubMed Central

Experimental study was made by keeping human peripheral blood lymphocytes under simulated microgravity in a Rotary Cell Culture System bioreactor to investigate the changes that occur in the number of chromosomes, the expression rate of chromosome fragile site, and the expressions of DNA replication- and repair-related genes. Experimental results indicate simulated microgravity has no effect on the numerical chromosome instability of human peripheral blood lymphocytes, but it enhances the structural chromosome instability of human peripheral blood lymphocytes through the inhibition of DNA replication and the reduction of DNA repair. So, the mechanism of chromosome fragile site induced by simulated microgravity can be explained using the changes that occur in the chromosome structure of human peripheral blood lymphocytes, the DNA replication and repair under the effect of simulated microgravity.

Wei, Lijun; Liu, Chuanpeng; Kang, Li; Liu, Yufeng; Shi, Shuliang; Wu, Qiong; Li, Yu

2014-01-01

125

Toxicity of cylindrospermopsin in human lymphocytes: Proliferation, viability and cell cycle studies.  

PubMed

The global expansion of cylindrospermopsin (CYN) producing cyanobacteria in surface freshwater increases the risk of human exposure and poisoning. Following ingestion, CYN is transported with blood in general circulation to the liver and kidneys, and can potentially interact with immune system cells. In the present study, we investigated whether CYN (0.01-1.0?gml(-1)) can alter the function of human peripheral blood lymphocytes isolated from healthy donors. It was found that CYN demonstrates significant antiproliferative activity in lymphocytes during different phases of their activation. The most remarkable effects (decrease by>90%) were observed in lymphocytes exposed to 1?gml(-1) CYN at the beginning of activation. Further analyses revealed a cell-cycle arrest at G0/G1 and prolonged S phase in lymphocytes undergoing activation and significant apoptosis inducement in activated cells. Reduced abilities to fight pathogenic microorganisms or malignant cells should be taken into consideration in CYN exposure and risk assessments. PMID:24780216

Poniedzia?ek, Barbara; Rzymski, Piotr; Wiktorowicz, Krzysztof

2014-08-01

126

[Study of the changes in the expression of histocompatibility antigens on the monocyte surface in the evaluation of the macrophage component of the immune system in rheumatoid arthritis].  

PubMed

Peripheral blood monocytes from 23 healthy persons and 25 RA patients were studied by cytohistochemistry, indirect immunofluorescence and cytophotometry to reveal interrelationship between cellular function of the system of mononuclear phagocytes and the expression of HLA-complex antigens in health and in RA. An increase in the phagocytic and metabolic activity of circulating monocytes was shown to be associated with a degree of the activity of an inflammatory process. A decrease in the level of the expression of HLA antigens class I was established in parallel with the rearrangement of the numerical ratio of cells expressing low and high levels of class II HLA-molecules. A degree of disorders of the expression of HLA-molecules and monocytic function was associated with a degree of RA activity. PMID:3394104

Konenkov, V I; Naumov, Iu N; Mikheenko, T V; Shirinski?, V S

1988-01-01

127

Phase I Study of Ofatumumab, a Human Anti-CD20 Antibody, in Japanese Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma  

PubMed Central

Objectives Ofatumumab is a human IgG1? monoclonal antibody that targets a membrane proximal epitope encompassing the small and large loops of CD20. This Phase I study evaluated the safety, tolerability, efficacy and pharmacokinetics of ofatumumab monotherapy in Japanese patients with relapsed/refractory B-cell chronic lymphocytic leukemia and small lymphocytic lymphoma. Methods Ofatumumab was administered intravenously weekly for a total of eight doses (dose escalation: 500 and 1000 mg). Six patients (two chronic lymphocytic leukemia and four small lymphocytic lymphoma) were enrolled into two dose cohorts (500 mg, three patients; 1000 mg, three patients). All six patients received 300 mg ofatumumab at the first infusion and either 500 or 1000 mg at seven subsequent weekly infusions. Results No dose-limiting toxicities or serious adverse events were observed. Grade 3–4 adverse events observed were grade 3 lymphocytopenia (n = 1) and neutropenia (n = 1). Grade 1–2 infusion-related adverse events leading to temporary interruption of ofatumumab infusion were observed in all six patients on the first infusion day, and all patients completed the planned eight infusions. The overall response rate was 50% (3/6). Conclusions Ofatumumab was well tolerated at doses up to 1000 mg and showed preliminary evidence of activity in relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma, warranting further investigations. This study was registered at ClinicalTrials.gov (NCT00742144).

Ogura, Michinori; Hatake, Kiyohiko; Tobinai, Kensei; Uchida, Toshiki; Suzuki, Tatsuya; Terui, Yasuhito; Yokoyama, Masahiro; Maruyama, Dai; Mori, Masakazu; Jewell, Roxanne C.; Katsura, Koichi; Hotta, Tomomitsu

2013-01-01

128

Human monocytes CD36 and CD16 are signaling molecules. Evidence from studies using antibody-induced chemiluminescence as a tool to probe signal transduction.  

PubMed Central

A panel of monoclonal antibodies (mAb) directed against human monocyte surface antigens was tested for their capacity to mediate signal transduction by measuring luminol-enhanced chemiluminescence (CL). The response patterns fell into three categories. The mAb Mo4, OKM3, OKM6 and antibodies specific for Fc receptor (FcR) type I and II did not mediate signal transduction directly or were weak triggers, but upon second-order cross-linking by goat anti-mouse immunoglobulin (Ig) F(ab')2 or rabbit anti-mouse Ig, a strong CL response was induced. The mAb recognizing different epitopes on CD11b (complement receptor type III alpha chain) were unique in their ability to induce a CL response either by direct stimulation or by second-order cross-linking. The mAb 3G8 recognizing FcR type III (FcRIII; CD16) on a monocyte subpopulation and CD36-specific monoclonals directly elicited a CL response. A response of similar magnitude was obtained with 3G8 F(ab')2 or with intact 3G8. Furthermore, elutriation-centrifugation-purified monocytes were stimulated by 3G8 to a similar extent as unseparated mononuclear cells, whereas lymphocytes did not respond. This suggests that a FcRIII-expressing monocyte subpopulation may mediate effector functions, including the generation of reactive oxygen species, via FcRIII triggering. Our finding that anti-CD36 F(ab')2 directly induces an oxidative burst is the first evidence that CD36 itself is a trigger molecule. CD36, which is thought to interact with erythrocytes infected with Plasmodium falciparum and with thrombospondin, may constitute a signal-transducing element and thus may have functions extending beyond mediation of adherence. The present CL system constitutes a simple assay for detecting mAb directed against monocyte surface signalling elements. Probing mAb for signal transduction requires suspended cells and antibodies in the fluid phase in order to avoid inadvertent FcR triggering, which may occur when cells are stimulated by surface-adherent whole antibodies.

Trezzini, C; Jungi, T W; Spycher, M O; Maly, F E; Rao, P

1990-01-01

129

Monocyte Subpopulations in Angiogenesis  

PubMed Central

Growing understanding of the role of the tumor microenvironment in angiogenesis has brought monocyte-derived cells into focus. Monocyte subpopulations are an increasingly attractive therapeutic target in many pathologic states, including cancer. Before monocyte-directed therapies can be fully harnessed for clinical use, understanding of monocyte-driven angiogenesis in tissue development and homeostasis, as well as malignancy, is required. Here, we provide an overview of the mechanisms by which monocytic subpopulations contribute to angiogenesis in tissue and tumor development, highlight gaps in our existing knowledge, and discuss opportunities to exploit these cells for clinical benefit.

Dalton, Heather J.; Armaiz-Pena, Guillermo; Gonzalez-Villasana, Vianey; Lopez-Berestein, Gabriel; Bar-Eli, Menashe; Sood, Anil K.

2014-01-01

130

Human monocytes recognize porcine endothelium via the interaction of galectin 3 and alpha-GAL.  

PubMed

Monocytes are one of the key inflammatory cells recruited to xenografts and play an important role in delayed xenograft rejection. Previous studies have demonstrated the ability of monocytes to bind to the major xenoantigen Gal-alpha(1,3)Gal-beta(1,4)GlcNAc-R; however, the receptor that mediates this interaction has yet to be identified. We provide evidence that it is Galectin-3, a approximately 30-kDa lectin that recognizes beta-galactosides (Gal-beta(1-3/4)GlcNAc) and plays diverse roles in many physiological and pathological events. Human monocyte binding is strikingly increased on porcine aortic endothelial cells (PAEC), which express high levels of Gal-alpha(1,3)Gal-beta(1,4)GlcNAc-R, compared with human aortic endothelial cells. Human monocytes obtained from healthy donors bind to Gal-alpha(1,3)Gal-beta(1,4)GlcNAc-R at variable intensities. This variation of binding intensity was consistent and reproducible in individual donors. Galectin-3 is mainly expressed in human monocytes, not lymphocytes. Purified Galectin-3 is able to bind directly to Gal-alpha(1,3)Gal-beta(1,4)GlcNAc-R. Galectin-3 can also be affinity isolated from monocytes (and not lymphocytes) using an Gal-alpha(1,3)Gal-beta(1,4)GlcNAc-R-biotin/streptavidin-bead pull-down system. Soluble Galectin-3 binds preferentially to PAEC vs human aortic endothelial cells, and this binding can be inhibited by lactose, indicating dependence on the carbohydrate recognition domain of Galectin-3. Gal-alpha(1,3)Gal-beta(1,4)GlcNAc-R is at least partly responsible for this phenomenon, as binding decreased after digestion of PAEC with alpha-galactosidase. Furthermore, monocytes pretreated with a blocking anti-Galectin-3 Ab show decreased adhesion to PAEC when compared with isotype control in a parallel plate flow chamber perfusion assay. Thus, we conclude that Galectin-3 expressed in human monocytes is a receptor for the major xenoantigen (Gal-alpha(1,3)Gal-beta(1,4)GlcNAc-R), expressed on porcine endothelial cells. PMID:16818789

Jin, Rongyu; Greenwald, Allen; Peterson, Mark D; Waddell, Thomas K

2006-07-15

131

Comparative study on saponin fractions from Panax notoginseng inhibiting inflammation-induced endothelial adhesion molecule expression and monocyte adhesion  

PubMed Central

Background Panax notoginseng is commonly used for the treatment of cardiovascular diseases in China. The present study investigates the effects of three different saponin fractions (ie total saponins, PNS; protopanaxadiol-type saponin, PDS; and protopanaxatriol-type saponin, PTS) and two major individual ingredients (ie ginsenoside Rg1 and Rb1) from P. notoginseng on the endothelial inflammatory response in vitro and in vivo. Methods Recombinant human tumor necrosis factor-? (TNF-?) was added to the culture medium of human coronary artery endothelial cells (HCAECs) to induce an inflammatory response. A cell adhesion assay was used to determine the effect of the P. notoginseng saponin fractions on endothelial-monocyte interaction. The cell adhesion molecule (CAMs) expression, including ICAM-1 and VCAM-1, in the protein level on the surface of endothelial cells were measured by cellular ELISA. CAMs expression in mRNA level was also assayed by qRT-PCR in the HCAECs and the aorta of rat fed with high cholesterol diet (HCD). Western blotting was used to detect effect of the saponin fractions on CAMs protein expression in HCAECs. In addition, nuclear translocation of p65, a surrogate marker for NF-?B activation, was measured by immunostaining. Results Three saponin fractions and two individual ginsenosides exhibited the inhibitory effects on monocyte adhesion on TNF-?-activated HCAECs and expression of ICAM-1 and VCAM-1 at both mRNA and protein levels in vitro. The saponin fractions exhibited a similar trend of the inhibitory effects on the mRNA expression of CAMs in the aorta of HCD-fed rat in vivo. These inhibitory effect of saponin fractions maybe attribute partially to the suppression of the TNF-?-induced NF-?B activation. Conclusion Our data demonstrate that saponin fractions (ie PNS, PDS and PTS) and major individual ginsenosides (ie Rg1 and Rb1) have potential anti-atherogenic effects. Among the tested saponin fractions, PDS is the most potent saponin fraction against TNF-?-induced monocyte adhesion as well as the expression of adhesion molecules in vitro and in vivo.

2011-01-01

132

Modulation of monocytic leukemia cell function and survival by high gradient magnetic fields and mathematical modeling studies.  

PubMed

The influence of spatially modulated high gradient magnetic fields on cellular functions of human THP-1 leukemia cells is studied. We demonstrate that arrays of high-gradient micrometer-sized magnets induce i) cell swelling, ii) prolonged increased ROS production, and iii) inhibit cell proliferation, and iv) elicit apoptosis of THP-1 monocytic leukemia cells in the absence of chemical or biological agents. Mathematical modeling indicates that mechanical stress exerted on the cells by high magnetic gradient forces is responsible for triggering cell swelling and formation of reactive oxygen species followed by apoptosis. We discuss physical aspects of controlling cell functions by focused magnetic gradient forces, i.e. by a noninvasive and nondestructive physical approach. PMID:24439412

Zablotskii, Vitalii; Syrovets, Tatiana; Schmidt, Zoe W; Dejneka, Alexandr; Simmet, Thomas

2014-03-01

133

Sources of heterogeneity in human monocyte subsets  

PubMed Central

Human monocytes are commonly defined and discriminated by the extent of their cell surface expression of CD14 and CD16, with associated differences in function and phenotype related to the intensity of expression of these markers. With increasing interest into the function and behaviour of monocytes, it is important to have a clear understanding of how differing strategies of analysis can affect results and how different protocols and population backgrounds can affect this highly morphogenic cell type. Using PBMCs from populations with differing ethnicities and histories of parasite exposure we have characterized monocyte phenotype based on intensity of CD14 and CD16 expression. Using the surface markers HLA-DR, CCR2 and CX3CR1, we compared monocyte phenotype between populations and further assessed changes in monocytes with freezing and thawing of PBMCs. Our results reveal that there is a progression of surface marker expression based on intensity of CD14 or CD16 expression, stressing the importance of careful gating of monocyte subtypes. Freezing and thawing of the PBMCs has no effect generally on the monocytes, although it does lead to a decrease in CD16 and CX3CR1 expression. We show that there are differences in the monocyte populations based on ethnicity and history of exposure to the common parasites Plasmodium falciparum and Schistosoma haematobium. This study highlights that blood monocytes consist of a continuous population of cells, within which the dominant phenotype may vary dependent on the background of the study population. Comparing results from monocyte studies therefore needs to be done with great care, as ethnic background of donor population, gating strategy and processing of PBMCs may all have an effect on outcome of monocyte phenotype.

Appleby, Laura J.; Nausch, Norman; Midzi, Nicholas; Mduluza, Takafira; Allen, Judith E.; Mutapi, Francisca

2013-01-01

134

Multiphoton intravital microscopy to study lymphocyte motility in lymph nodes.  

PubMed

Intravital microscopy (IVM) allows for the direct in vivo visualization of dynamic biological processes in their physiological context at high spatial and temporal resolution. Novel nonlinear optical imaging modalities, most prominently multiphoton microscopy, have extended the spectrum of cellular functions amenable to IVM investigation to include migration and cell-cell interactions occurring deep inside the highly light-scattering environments of solid tissues, which had so far been inaccessible to conventional microscopy techniques. This has led to important new insights into immune cell behavior at steady state, as well as their change in behavior during an immune response. Here, we describe in detail a technique that allows for the monitoring of lymphocyte motility in the lymph nodes of mice at the single cell level using multiphoton intravital microscopy (MP-IVM). PMID:21909917

Murooka, Thomas T; Mempel, Thorsten R

2012-01-01

135

Oxidative mechanisms of monocyte-mediated cytotoxicity.  

PubMed Central

Human monocytes stimulated with phorbol myristate acetate were able to rapidly destroy autologous erythrocyte targets. Monocyte-mediated cytotoxicity was related to phorbol myristate acetate concentration and monocyte number. Purified preparations of lymphocytes were incapable of mediating erythrocyte lysis in this system. The ability of phorbol myristate acetate-stimulated monocytes to lyse erythrocyte targets was markedly impaired by catalase or superoxide dismutase but not by heat-inactivated enzymes or albumin. Despite a simultaneous requirement for superoxide anion and hydrogen peroxide in the cytotoxic event, a variety of hydroxyl radical and singlet oxygen scavengers did not effect cytolysis. However, tryptophan significantly inhibited cytotoxicity. The myeloperoxidase inhibitor cyanide enhanced erythrocyte destruction, whereas azide reduced it modestly. The inability of cyanide to reduce cytotoxicity coupled with the protective effect of superoxide dismutase suggests that cytotoxicity is independent of the classic myeloperoxidase system. We conclude that monocytes, stimulated with phorbol myristate acetate, generate superoxide anion and hydrogen peroxide, which together play an integral role in this cytotoxic mechanism.

Weiss, S J; LoBuglio, A F; Kessler, H B

1980-01-01

136

Detection and properties of the human proliferative monocyte subpopulation  

Microsoft Academic Search

Peripheral blood monocyte subpopula- tions have been reported and can give rise to di- verse, differentiated phenotypes. A subpopula- tion(s) of human monocytes can proliferate in vitro in response to macrophage-colony stimulating fac- tor (M-CSF; or CSF-1). This population, termed the proliferative monocyte (PM), is presumably less mature than other monocytes; however, it has not been defined further. Previous studies

Felix I. L. Clanchy; Alice C. Holloway; Roya Lari; Paul U. Cameron; John A. Hamilton

2006-01-01

137

Hematologic variables and venous thrombosis: red cell distribution width and blood monocyte count are associated with an increased risk  

PubMed Central

Recent studies suggest that leukocytes and erythrocytes play a role in coagulation. However, whether leukocytes, erythrocytes and other hematologic variables are associated with risk of venous thrombosis is not well known. To study this, we used data from 2473 patients with venous thrombosis and 2935 controls. The variables assessed were: total leukocytes, granulocytes, lymphocytes, monocytes, hematocrit, hemoglobin, erythrocytes and red cell indices (mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration and red cell distribution width). We found a strong dose-response relation for higher red cell distribution width and monocyte count with risk of venous thrombosis, with odds ratios of 3.1 (95% confidence interval, 2.0–4.8) and 2.8 (95% confidence interval, 1.3–5.8), respectively, after adjustment for age, sex, C-reactive protein level, malignancy and co-morbidities. Monocyte count and red cell distribution width were associated with venous thrombosis even within reference ranges. A low monocyte count (<0.12×109/L) was associated with a lower risk of venous thrombosis after full adjustment (odds ratios 0.6; 95% confidence interval, 0.4–0.8). In summary, high red cell distribution width and blood monocyte count, two parameters that are inexpensive and easily obtainable, were clearly associated with an increased risk of venous thrombosis. Future studies should evaluate the underlying mechanism and the use of these variables in prediction models for first and recurrent thrombosis.

Rezende, Suely Meireles; Lijfering, Willem M.; Rosendaal, Frits R.; Cannegieter, Suzanne C.

2014-01-01

138

Impaired monocyte activation in schizophrenia.  

PubMed

An inflammatory process is hypothesized in schizophrenia. Innate immunity, in particular the monocyte/macrophage system, has rarely been studied in this disorder, although alterations in microglia indicate a role for this system. Increased monocyte numbers have repeatedly been described. Toll-like receptors (TLRs) mediate the activation of monocytes. We studied the expression of the toll-like receptors TLR-2, TLR-3 and TLR-4 on CD14(+) monocytes in 31 schizophrenia patients and 31 sex- and age-matched healthy controls. Blood samples were taken and stimulated with either lipopolysaccharides (LPS), to mimic a bacterial infection, or polyI:C, to mimic a viral infection. Moreover, the intracellular concentration of interleukin-1ß (IL-1ß) in CD33(+) monocytes was estimated before and after stimulation. The intracellular concentrations of IL-1ß and the TLR surface markers were analyzed by flow cytometry. Receptor expression of TLR-3 and TLR-4, but not of TLR-2, was significantly higher in the schizophrenia patients. After stimulation, patients showed less increase in the expression of TLR-3 and TLR-4 than controls did. The IL-1ß concentration was significantly lower in patients both before and after stimulation with polyI:C, and there was a trend towards a lower concentration after LPS stimulation. The higher expression of TLR-3 and TLR-4 receptors might compensate for a functional deficit, and the lower intracellular concentrations of IL-1ß might reflect the blunted monocytic function in schizophrenia. The immunological dysfunctions might be associated with a poor clearance of pathogens in schizophrenia, which in turn could lead to a low-grade inflammatory process. PMID:22429483

Müller, Norbert; Wagner, Jenny K; Krause, Daniela; Weidinger, Elif; Wildenauer, Agnes; Obermeier, Michael; Dehning, Sandra; Gruber, Rudolf; Schwarz, Markus J

2012-08-15

139

Chlorobenzenes, lindane and dieldrin induce apoptotic alterations in human peripheral blood lymphocytes (in vitro study).  

PubMed

In this study, we have assessed apoptotic effect of 1,2,4-trichlorobenzene, hexachlorobenzene, lindane and dieldrin on human peripheral blood lymphocytes. We observed an increase in ROS formation and a decrease in mitochondrial transmembrane potential in the cells incubated with low concentrations of all compounds studied, in particular lindane and dieldrin. ROS formation and changes in mitochondrial transmembrane potential may have influenced caspase-3 activation, a crucial enzyme in the apoptotic process. Moreover, chlorobenzenes, and in particular lindane and dieldrin changed cells' membrane permeability and induced phosphatidylserine translocation, which confirmed that they are capable of inducing apoptosis in human lymphocytes. Apoptotic changes in human lymphocytes provoked by biologically relevant concentrations of these substances suggest that they may disturb function of immunological system especially among people occupationally exposed to their action. PMID:24077485

Micha?owicz, Jaromir; Mokra, Katarzyna; Rosiak, Karolina; Sici?ska, Paulina; Bukowska, Bo?ena

2013-11-01

140

Studies on the nature of EA binding by lymphocytes from rheumatoid arthritis patients  

PubMed Central

Investigation of the nature of the increased erythrocyte-antibody (EA) binding activity of peripheral blood lymphocytes (PBL) from rheumatoid arthritis (RA) patients reported in the preceding paper has revealed that IgG is the active class of antibody in this rosette formation. Some IgM binding also occurs. SRBC sensitized with F(ab)2 preparations of IgG do not give rosette formation even at high concentrations. EA binding is inhibited by prior incubation of lymphocytes with heat-aggregated human IgG but antigen-antibody complexes did not give significant inhibition. The majority of these rosettes were found to be stable at 4°C and room temperature but labile at 37°C. Enzyme studies with pronase, trypsin, neuraminidase and treatment with sodium azide gave results strongly supporting the conclusion that the increased binding observed is increased Fc-receptor activity. This activity appears not to be a result of Fc binding by cell-bound rheumatoid factor. A range of titres of antibody and of IgG was used to sensitize erythrocytes to form EA and the enhanced EA-rosette formation by PBL from RA patients occurred throughout the range of concentrations of sensitizing antibody. Significantly more EA were bound by individual lymphocytes from RA patients than control subjects. This data suggest that the Fc receptors on RA lymphocytes are more avid for EA than receptors on lymphocytes from healthy people.

Sharpin, Rosemary K. C.; Wilson, J. D.

1977-01-01

141

The use of the alkaline comet assay with lymphocytes in human biomonitoring studies  

Microsoft Academic Search

We reviewed the data of 45 alkaline comet assay studies with lymphocytes published during the last three years with the objective of monitoring human exposure to genotoxic agents as a result of occupation, drug treatment, diseases or environmental pollution. The strengths of the studies were that: (i) a lot of data could be obtained within a relatively short period of

Floriane Faust; Fekadu Kassie; Siegfried Knasmüller; Rolf Hasso Boedecker; Marion Mann; Volker Mersch-Sundermann

2004-01-01

142

A new method for separating lymphocytes and granulocytes from human peripheral blood using programmed gradient sedimentation in an isokinetic gradient  

PubMed Central

Isopycnic sedimentation and programmed rate-zonal sedimentation in an isokinetic gradient of Ficoll (polysucrose) in tissue culture medium were used for the purification of individual kinds of cells from human peripheral blood. Following centrifugation in the isokinetic gradient, lymphocytes were 99.9±0.1 per cent and granulocytes 90.1±3.8 per cent of nucleated cells in their respective fractions. While monocytes were concentrated in one zone of the gradient, they were not as highly purified as monocytes prepared using established methods. Purification of lymphocytes and granulocytes using the isokinetic gradient offers one of the most effective and rapid means for obtaining purified sterile lymphocytes and granulocytes for in vitro or biochemical studies. ImagesFIG. 3FIG. 4FIG. 2

Pretlow, T. G.; Luberoff, D. E.

1973-01-01

143

Studies on the glycolipids of sheep thymus and of normal and concanavalin A-stimulated sheep peripheral lymphocytes.  

PubMed

The neutral glycolipids and gangliosides of sheep thymus and of sheep peripheral lymphocytes were compared. The patterns of both of these major classes of glycolipids were more complex in thymus than in the lymphocytes. The incorporation of radioactivity from D-[1-14C]galactose into the individual glycolipids of control and concanavalin A-stimulated sheep peripheral lymphocytes was also studied. A marked enhancement of incorporation into trihexosylceramide and an alteration of the pattern of incorporation into gangliosides were noted in the mitogen-treated cells. The results suggest that significant alterations of glycolipid composition and metabolism may occur during at least certain stages of lymphocyte differentiation. PMID:949491

Narasimhan, R; Hay, J B; Greaves, M F; Murray, R K

1976-06-22

144

Monocyte-endothelial adhesion in chronic rheumatoid arthritis. In situ detection of selectin and integrin-dependent interactions.  

PubMed Central

Blood monocytes are the principal reservoir for tissue macrophages in rheumatoid synovitis. Receptor-mediated adhesive interactions between circulating cells and the synovial venules initiate recruitment. These interactions have been studied primarily in cultured endothelial cells. Thus the functional activities of specific adhesion receptors, such as the endothelial selectins and the leukocytic integrins, have not been evaluated directly in diseased tissues. We therefore examined monocyte-microvascular interactions in rheumatoid synovitis by modifying the Stamper-Woodruff frozen section binding assay initially developed to study lymphocyte homing. Specific binding of monocytes to venules lined by low or high endothelium occurred at concentrations as low as 5 x 10(5) cells/ml. mAbs specific for P-selectin (CD62, GMP-140/PADGEM) blocked adhesion by > 90% in all synovitis specimens examined. In contrast, P-selectin-mediated adhesion to the microvasculature was either lower or absent in frozen sections of normal foreskin and placenta. mAbs specific for E-selectin (ELAM-1) blocked 20-50% of monocyte attachment in several RA synovial specimens but had no effect in others. mAbs specific for LFA-1, Mo1/Mac 1, the integrin beta 2-chain, and L-selectin individually inhibited 30-40% of adhesion. An mAb specific for the integrin beta 1-chain inhibited the attachment of elutriated monocytes up to 20%. We conclude that P-selectin associated with the synovial microvasculature initiates shear-resistant adhesion of monocytes in the Stamper-Woodruff assay and stabilizes bonds formed by other selectins and the integrins. Thus the frozen section binding assay permits direct evaluation of leukocyte-microvascular adhesive interactions in inflamed tissues and suggests a prominent role for P-selectin in monocyte recruitment in vivo. Images

Grober, J S; Bowen, B L; Ebling, H; Athey, B; Thompson, C B; Fox, D A; Stoolman, L M

1993-01-01

145

Class II major histocompatibility complex antigen expression on peripheral blood monocytes in patients with inflammatory bowel disease.  

PubMed Central

Macrophage major histocompatibility complex (MHC) class II antigen expression is associated with defective antigen presentation to T lymphocytes in animals and is predictive of patient outcome after major trauma or sepsis. In this study, class II antigen (HLA-DR and DQ) expression on peripheral blood monocytes was investigated in patients with inflammatory bowel disease in relation to disease activity and outcome. The percentage positivity and fluorescent intensity of expression of HLA-DR and DQ antigens on monocytes were determined in whole blood samples using dual colour immunofluorescence labelling and flow cytometry. Disease activity was assessed using clinical and laboratory indices. There was no significant difference in percentage positivity or fluorescent intensity of class II antigen expression between patients with Crohn's disease, those with ulcerative colitis, and healthy volunteers. The percentage of monocytes displaying HLA-DR positivity was significantly decreased in patients with active ulcerative colitis (active %: 49.5 (5.6); inactive %: 78.9 (6.9); p = 0.01). Data expressed as mean (SEM). In patients requiring surgical resection of diseased bowel, the percentage of monocytes displaying HLA-DR positivity (51.9 (4.0) %) was significantly reduced compared with patients receiving medical treatment alone (81.1 (3.5) %; p < 0.001). Reduced monocyte HLA-DR expression is therefore associated with disease activity and seems to predict outcome in patients with inflammatory bowel disease.

Gardiner, K R; Crockard, A D; Halliday, M I; Rowlands, B J

1994-01-01

146

2-Chlorodeoxyadenosine (cladribine) induces apoptosis in human monocyte-derived dendritic cells.  

PubMed

2-Chlorodeoxyadenosine (cladribine, CdA) is an immunosuppressive drug that is licensed to treat hairy cell leukaemia, and has been shown recently to have beneficial effects in patients with multiple sclerosis (MS). The therapeutic effects of CdA have been suggested to be mediated partly through its potent toxicity towards lymphocytes. However, the effects of CdA on other immune cells are poorly understood. In the present study, we investigated the effects of CdA on the induction of apoptosis in human monocytes, monocyte-derived immature (ImDC) and mature (mDC) dendritic cells. Treatment of monocytes with CdA strongly induced apoptosis after 24 h, while apoptosis induction in DC was evident after 72 h. Furthermore, CdA treatment strongly induced caspase-3 and caspase-9 in monocytes, whereas activation of caspases was undetected in DC. The mitochondrial membrane potential in DC was reduced significantly after CdA treatment. DNA hypodiploid assessment showed fragmented nuclei in DC after CdA treatment together with activation of p53 protein. These results revealed that CdA induces caspase-independent apoptosis in DC and suggest cell type specific effects of CdA. This mechanism may contribute to the effect of CdA in autoimmune diseases. PMID:23607690

Singh, V; Prajeeth, C K; Gudi, V; Bénardais, K; Voss, E V; Stangel, M

2013-08-01

147

Osteoclastic differentiation of mouse and human monocytes in a plasma clot/biphasic calcium phosphate microparticles composite.  

PubMed

We recently demonstrated that blood clotted around biphasic calcium phosphate (BCP) microparticles constituted a composite biomaterial that could be used for bone defect filling. In addition, we showed that mononuclear cells, i.e. monocytes and lymphocytes, play a central role in the osteogenic effect of this biomaterial. Hypothesizing that osteoclast progenitors could participate to the pro-osteogenic effect of mononuclear cells we observed previously, we focus on this population through the study of mouse monocyte/macrophage cells (RAW264.7 cell line), as well as human pre-osteoclastic cells derived from mononuclear hematopoietic progenitor cells (monocytes-enriched fraction from peripheral blood). Using monocyte-derived osteoclast progenitors cultured within plasma clot/BCP microparticles composite, we aimed in the present report at the elucidation of transcriptional profiles of genes related to osteoclastogenesis and to bone remodelling. For both human and mouse monocytes, real-time PCR experiments demonstrated that plasma clot/BCP scaffold potentiated the expression of marker genes of the osteoclast differentiation such as Nfactc1, Jdp2, Fra2, Tracp and Ctsk. By contrast, Mmp9 was induced in mouse but not in human cells, and Ctr expression was down regulated for both species. In addition, for both mouse and human precursors, osteoclastic differentiation was associated with a strong stimulation of VegfC and Sdf1 genes expression. At last, using field-emission scanning electron microscopy analysis, we observed the interactions between human monocytes and BCP microparticles. As a whole, we demonstrated that plasma clot/BCP microparticles composite provided monocytes with a suitable microenvironment allowing their osteoclastic differentiation, together with the production of pro-angiogenic and chemoattractant factors. PMID:21154244

Mouline, Caroline C; Quincey, Danielle; Laugier, Jean-Pierre; Carle, Georges F; Bouler, Jean-Michel; Rochet, Nathalie; Scimeca, Jean-Claude

2010-01-01

148

Safety and Tolerability Study of PCI-32765 in B Cell Lymphoma and Chronic Lymphocytic Leukemia  

ClinicalTrials.gov

B-cell Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma; Diffuse Well-differentiated Lymphocytic Lymphoma; B Cell Lymphoma; Follicular Lymphoma,; Mantle Cell Lymphoma; Non-Hodgkin's Lymphoma; Waldenstrom Macroglobulinemia; Burkitt Lymphoma; B-Cell Diffuse Lymphoma

2013-10-30

149

CYTOTOXIC T-LYMPHOCYTE IMMUNOTHERAPY FOR OVARIAN CANCER: A PILOT STUDY  

PubMed Central

The objective was to evaluate the toxicity and feasibility of intraperitoneal (IP) infusion of tumor-specific cytotoxic T-lymphocytes (CTL) as therapy for recurrent ovarian cancer, and to determine if repetitive cycles of CTL generation and infusion measurably increases the host’s ovarian cancer immune response. In this study, seven subjects with recurrent ovarian cancer confined to the peritoneal cavity underwent up to 4 cycles, each cycle beginning with a leukapheresis for collection of precursor lymphocytes, which were stimulated in vitro with MUC1, a tumor-specific antigen found commonly in ovarian cancer cells. The resulting new CTL for each cycle were re-introduced into the host via IP infusion. Immunological parameters (killer cells, cytokine production, memory T-lymphocytes and natural killer (NK) cells) were studied. Toxicity, CA-125, and survival data were also evaluated. The tumor marker CA-125 was non statistically significantly reduced after the first month of immunotherapy. However, after that, it rose. Killer cells, cytokine production and memory T-lymphocytes increased after the first cycle of stimulation, but plateaued or reduced thereafter. The percent of NK cells inversely correlated with other immune parameters. Median survival was 11.5 months. One subject is free of disease since December, 2000. Multiple cycles, beyond one cycle, of T-cell stimulation followed by adoptive T cell infusion, may not enhance the in vivo immune response.

Wright, Stephen E.; Rewers-Felkins, Kathleen A.; Quinlin, Imelda S.; Phillips, Catherine A.; Townsend, Mary; Philip, Ramila; Dobrzanski, Mark J.; Lockwood-Cooke, Pamela R.; Robinson, William

2012-01-01

150

Static adhesion assay for the study of integrin activation in T lymphocytes.  

PubMed

T lymphocyte adhesion is required for multiple T cell functions, including migration to sites of inflammation and formation of immunological synapses with antigen presenting cells. T cells accomplish regulated adhesion by controlling the adhesive properties of integrins, a class of cell adhesion molecules consisting of heterodimeric pairs of transmembrane proteins that interact with target molecules on partner cells or extracellular matrix. The most prominent T cell integrin is lymphocyte function associated antigen (LFA)-1, composed of subunits ?L and ?2, whose target is the intracellular adhesion molecule (ICAM)-1. The ability of a T cell to control adhesion derives from the ability to regulate the affinity states of individual integrins. Inside-out signaling describes the process whereby signals inside a cell cause the external domains of integrins to assume an activated state. Much of our knowledge of these complex phenomena is based on mechanistic studies performed in simplified in vitro model systems. The T lymphocyte adhesion assay described here is an excellent tool that allows T cells to adhere to target molecules, under static conditions, and then utilizes a fluorescent plate reader to quantify adhesiveness. This assay has been useful in defining adhesion-stimulatory or inhibitory substances that act on lymphocytes, as well as characterizing the signaling events involved. Although described here for LFA-1 - ICAM-1 mediated adhesion; this assay can be readily adapted to allow for the study of other adhesive interactions (e.g. VLA-4 - fibronectin). PMID:24961998

Strazza, Marianne; Azoulay-Alfaguter, Inbar; Pedoeem, Ariel; Mor, Adam

2014-01-01

151

Making a difference: Monocyte Heterogeneity in Cardiovascular Disease  

PubMed Central

Monocytes are frequently described as bone marrow-derived precursors of macrophages. Although many studies support this view, we now appreciate that monocytes neither develop exclusively in the bone marrow nor give rise to all macrophages and dendritic cells. In addition to differentiating to specific leukocyte populations, monocytes, as monocytes, are functionally and ontogenically heterogeneous. In this review we will focus on the development and activity of monocytes and their subsets in mice (Ly-6Chigh/low) and humans (CD14+/dim/? CD16+/?) in the context of atherosclerosis and its complications.

Hilgendorf, Ingo; Swirski, Filip K

2012-01-01

152

From proliferation to proliferation: monocyte lineage comes full circle.  

PubMed

Monocytes are mononuclear circulating phagocytes that originate in the bone marrow and give rise to macrophages in peripheral tissue. For decades, our understanding of monocyte lineage was bound to a stepwise model that favored an inverse relationship between cellular proliferation and differentiation. Sophisticated molecular and surgical cell tracking tools have transformed our thinking about monocyte topo-ontogeny and function. Here, we discuss how recent studies focusing on progenitor proliferation and differentiation, monocyte mobilization and recruitment, and macrophage differentiation and proliferation are reshaping knowledge of monocyte lineage in steady state and disease. PMID:24435095

Swirski, Filip K; Hilgendorf, Ingo; Robbins, Clinton S

2014-03-01

153

The Use of Human T-Lymphocyte Clones to Study T-Cell Function in Allergic Contact Dermatitis to Urushiol  

Microsoft Academic Search

Allergic contact dermatitis to poison ivy (Toxicodendron radicans) is believed to be mediated by T lymphocytes specific for the hapten urushiol. Activated T lymphocytes may produce pathology by a variety of mechanisms including direct cytotoxicity, production of lymphokines, recruitment of non-specific effector cells, non-specific cytotoxicity, and possibly autologous DR reactivity. The regulation and pathogenesis of this condition was studied by

Richard S. Kalish

1990-01-01

154

Proteome Comparison of Alveolar Macrophages with Monocytes Reveals Distinct Protein Characteristics  

Microsoft Academic Search

Alveolar macrophages (AMs) are a subset of tissue macrophages situated in the alveolar milieu. Compared with their precursor blood monocytes, AMs exhibit distinct physiologic functions unique to their anatomic location. However, the molecular details that control monocyte differentiation into AMs remain unknown. This study employed a proteomic approach to define protein characteristics that distinguish AMs from monocytes. AMs and monocytes

Ming Jin; Judy M. Opalek; Clay B. Marsh; Haifeng M. Wu

2004-01-01

155

Adaptation of Ehrlichia sennetsu to canine blood monocytes: preliminary structural and serological studies with cell culture-derived Ehrlichia sennetsu.  

PubMed Central

Ehrlichia sennetsu, the causative agent of human sennetsu rickettsiosis, was successfully propagated in primary canine blood monocyte cultures. The growth cycle of this organism appears to be similar to that of Ehrlichia canis. The antigen derived from our E. sennetsu cultures was used to develop an indirect fluorescent antibody test for detection and titration of serum antibodies to the organism. Using this test system, we found that five human serum samples obtained from patients clinically diagnosed as having sennetsu rickettsiosis were positive for anti-E. sennetsu antibodies. In addition, 29% of the serum samples obtained from 200 patients having a fever of unknown origin and residing in various regions of Malaysia were also serologically positive. All sera from apparently healthy individuals were negative in the test. Dogs inoculated with cell culture-adapted E. sennetsu developed a significant specific antibody titer to E. sennetsu, and the organism was subsequently isolated from their blood. These animals showed no clinical evidence of disease. The possibility of a higher prevalence of human sennetsu rickettsiosis in Southeast Asia and the potential usefulness of the canine model for studies of human sennetsu rickettsiosis are discussed. Images

Holland, C J; Ristic, M; Huxsoll, D L; Cole, A I; Rapmund, G

1985-01-01

156

Radiation effects on cultured human monocytes and on monocyte-derived macrophages  

SciTech Connect

Prior to administration, leukocyte transfusions are commonly irradiated with up to 5,000 R to eliminate lymphocytes and thereby prevent graft-versus-host disease in the recipient. It has been widely believed that phagocytes are resistant to this irradiation. In a recent report, it was noted that phagocyte oxidative metabolism was compromised during preparation of white cells for transfusion. As part of the effort to examine the basis for this inhibition of phagocyte function during white cell preparation, an assessment was made of the effects of irradiation on the long-lived monocytes that have been shown to persist at inflammatory foci posttransfusion. Human monocytes were irradiated for up to 3 min, receiving 2,500-5,000 R. This irradiation damaged human monocytes, significantly decreasing their in vitro survival for the first 3 wk of culture, and growth as assessed by two-dimensional cell size measurements during the first 2 wk of culture. Despite smaller cell size, total cell protein was significantly increased over time in irradiated cultures. Extracellular release of lysozyme and beta-glucuronidase per cell was not affected by irradiation, but extracellular lactate dehydrogenase (LDH) release was significantly increased after irradiation. Irradiated monocytes killed Listeria monocytogenes at a slower rate than the nonirradiated controls. Thus, the data indicate that irradiation in doses used to prevent graft-versus-host disease in leukocyte transfusion recipients has a deleterious effect on in vitro human monocyte survival and function.

Buescher, E.S.; Gallin, J.I.

1984-06-01

157

Monocyte Chemoattractant Protein-1 (MCP-1): An Overview  

PubMed Central

Chemokines constitute a family of chemoattractant cytokines and are subdivided into four families on the basis of the number and spacing of the conserved cysteine residues in the N-terminus of the protein. Chemokines play a major role in selectively recruiting monocytes, neutrophils, and lymphocytes, as well as in inducing chemotaxis through the activation of G-protein-coupled receptors. Monocyte chemoattractant protein-1 (MCP-1/CCL2) is one of the key chemokines that regulate migration and infiltration of monocytes/macrophages. Both CCL2 and its receptor CCR2 have been demonstrated to be induced and involved in various diseases. Migration of monocytes from the blood stream across the vascular endothelium is required for routine immunological surveillance of tissues, as well as in response to inflammation. This review will discuss these biological processes and the structure and function of CCL2.

Deshmane, Satish L.; Kremlev, Sergey; Amini, Shohreh

2009-01-01

158

Variation in the monocyte proteome.  

PubMed

We have determined the variability of the monocyte proteome and identified those proteins that demonstrate the greatest variation in the general control population. Monocytes were isolated from 18 healthy (9 male and 9 female) donors ages 18-50 and with no known genetic or blood disorder. A combination of Ficoll-Paque PLUS density centrifugation of cells found in the buffy coat and positive selection with monoclonal antibodies against CD14, coupled to magnetic beads, led to >98% purity of monocytes. A 100,000 g microsomal membrane fraction or 100,000 g supernatant fraction from a control subject was compared to the equivalent fractions from a distinct control subject by two-dimensional differential gel electrophoresis (2D DIGE). Those protein spots that demonstrated Cy3-/Cy5- ratios greater than 2.5-fold in at least one experiment were selected for further statistical analysis. We determined variability for 31 cytosolic and 12 membrane protein spots. Proteins have been identified for 27 of the cytosolic protein spots and 9 of the microsomal membrane protein spots by in-gel digestion with trypsin followed by reverse-phase high-performance liquid chromatography in line with tandem mass spectrometry. We identified 24 distinct monocyte proteins that demonstrated the greatest variability in this general control population. The proteins demonstrating the greatest variance in the cytosolic fraction were enolase-1 and WD (tryptophan-aspartate) repeat-containing protein 1, and in the membrane fraction they were lamin B1 and L-plastin. This study demonstrates the importance of considering variance in the control population when performing future protein profiling comparisons of monocytes derived from disease versus control populations. PMID:17609514

Hryniewicz-Jankowska, Anita; Choudhary, Pankaj K; Goodman, Steven R

2007-07-01

159

Induction of selective biological responses to chemoattractants in a human monocyte-like cell line.  

PubMed Central

The availability of monocyte cell lines that can be induced to differentiate in a predictable fashion can provide important tools for the study of the biochemical mechanisms of specific cellular responses. The U937 human monocyte cell line was previously shown to differentiate into chemotactically responsive cells when incubated with supernatants of lectin-stimulated lymphocytes (conditioned medium). Considering the heterogeneous nature of stimulated lymphocyte supernatants, attempts were made to identify well-defined agents that could reproducibly induce U937 cell differentiation. Both dimethyl sulfoxide and dibutyryl cAMP induced expression of receptors for the N-formylated oligopeptide chemoattractants in U937 cells. Unstimulated U937 cells contained no detectable receptors. After cells were exposed to 1 mM dibutyryl cAMP, 1.3% dimethyl sulfoxide, or 5% conditioned medium for 72 h, the average number of oligopeptide chemoattractant receptors per U937 cell was 33,000, 4,000, and 3,400, respectively. Specific binding proteins for the chemoattractants were identified by covalent affinity labeling on the differentiated U937 cells as well as on normal human monocytes. Cells exposed to conditioned medium responded chemotactically, secreted lysosomal enzymes, and formed superoxide anion when incubated with the chemoattractant. Treatment of U937 cells with dibutyryl cAMP resulted in the most reproducible and rapid increase in the number of chemoattractant receptors as well as in chemotactic responsiveness. The receptors on dibutyryl cAMP-treated cells and on dimethyl sulfoxide-treated cells initiated chemotaxis and lysosomal enzyme secretion in response to chemoattractants, but not the formation of superoxide anion. These findings demonstrate that development of the chemotactic and respiratory burst functions during the differentiation of a monocyte-like cell line can occur independently. Images

Kay, G E; Lane, B C; Snyderman, R

1983-01-01

160

THE INTERACTION BETWEEN HUMAN MONOCYTES AND RED CELLS  

PubMed Central

Red cells coated with IgG globulin were bound firmly to human mononuclear cells and formed rosettes. Rosette formation occurred when red cells were coated with IgG attached either immunologically (anti-D, anti-penicillin, or Donath-Landsteiner antibodies) or nonimmunologically with chromic chloride; no attachment was observed with cells coated with albumin. Rosette formation was blocked by pretreatment of white cells with sulfhydryl-binding reagents. Metabolic inhibitors did not prevent red cell adherence. White cells of other primates demonstrated a high degree of species specificity. Ultrastructural studies showed that the predominant leukocytes involved in rosette formation were monocytes, but some cells with characteristics of lymphocytes also formed rosettes. Considerable interdigitation of cell surfaces occurred at attachment sites and bound red cells appeared deformed. Thus, these studies confirm the presence of specific surface receptors for IgG on human monocytes and suggest that such receptors may provide a mechanism by which large numbers of red cells are eventually destroyed.

Abramson, N.; Lo Buglio, A. F.; Jandl, J. H.; Cotran, R. S.

1970-01-01

161

Monocyte B7 and Sialyl Lewis X modulates the efficacy of IL-10 down-regulation of LPS-induced monocyte tissue factor in whole blood.  

PubMed

Recent studies have investigated the use of anti-inflammatory cytokine, interleukin 10 (IL-10) to control the development of disseminated intravascular coagulation (DIC) in sepsis by down-regulation of monocyte tissue factor (MTF) induced by lipopolysaccharide (LPS) in the initial phase of the disease. In vitro and in vivo human studies have shown that a minimal (<1 h) delay in IL-10 treatment significantly reduces the cytokines ability to inhibit LPS-induced MTF expression and the end products of coagulation. In this whole blood in vitro study we investigated the role of lymphocyte and platelet interactions with monocytes to up-regulate MTF expression in the presence of IL-10 in the initial phase of exposure to LPS. Individual blockade of monocyte B7 or platelet P-selectin significantly (35%) reduced MTF expression (P<0.05). IL-10 showed a dose-dependent inhibition of LPS (0.1 microg/ml) induced MTF expression, with 56% inhibition at 1 ng/ml, maximizing at 5 ng/ml IL-10 (75%; P<0.05). Simultaneous exposure to LPS and IL-10 (1 ng/ml) or addition of IL-10 1 h after LPS, with individual B7 and P-selectin blockade significantly enhanced the inhibition of MTF expression by IL-10 (P<0.05). We conclude that the efficacy of IL-10 to control DIC could be enhanced by a simultaneous B7 and P-selectin blockade. PMID:9695978

Warnes, G; Biggerstaff, J P; Francis, J L

1998-07-01

162

[Are lymphocytic and collagenous colitis two forms of a single disease? Arguments taken from a biopsy quantitative study].  

PubMed

Collagenous colitis and lymphocytic colitis are defined by a clinicopathologic syndrome with chronic watery diarrhea, microscopic lesions of colonic biopsies, and normal barium enema and colonoscopy. A histopathological study was performed on multiple colorectal biopsies to compare 12 cases of collagenous colitis (defined by a subepithelial collagen thicker than 10 microns) and 7 cases of lymphocytic colitis (defined by a number of intraepithelial lymphocytes more than 20 per 100 epithelial cells at least in one biopsied site). The study included a semiquantitative analysis of inflammatory infiltrate in the lamina propria, crypts distortion and epithelial detachment. The number of intraepithelial lymphocytes per 100 epithelial cells was determined in surface epithelium and crypts. The subepithelial collagen thickening was studied by computerised morphometry. The intraepithelial lymphocytes, villous atrophy and thickness of the subepithelial collagen were also determined in gastric and duodenal biopsies. In collagenous colitis, the subepithelial collagenous thickness ranged from 10 to 40 microns in the colon (median 20.99 microns). In 4 cases of collagenous colitis, no thickening of the collagen plate was seen in the rectum. We found constant epithelial detachment and mucosal distortion. In lymphocytic colitis, the thickness of the subepithelial collagen ranged from 6 to 10 microns in 4 cases and was less than 6 microns in 3 cases (median 6.24 microns). The median number of intraepithelial lymphocytes in surface epithelium was 22.35 (range 18.2 to 40) in lymphocytic colitis versus 12.22 (range 4.6 to 24.4) in collagenous colitis. In conclusion, we observed an overlap of both the collagenous plate thickness and the number of intraepithelial lymphocytes in collagenous colitis and lymphocytic colitis. This result favours a unified histogenesis for these two entities. PMID:9090931

Cymes, K; Potet, F; Dauge-Geffroy, M C; Fléjou, J F; Rampal, A; Klein, O; Rampal, P; Goldfain, D; Rotenberg, A

1996-12-01

163

Soluble fibrin inhibits lymphocyte adherence and cytotoxicity against tumor cells: implications for cancer metastasis and immunotherapy.  

PubMed

Circulating soluble fibrin (sFn) is elevated in many cancer patients. It is a marker for ongoing disseminated intravascular coagulation and may have prognostic significance. We have demonstrated that sFn inhibited monocyte adherence and cytotoxicity by a mechanism involving blockade of monocyte alphaMbeta2 and tumor cell CD54. It was, therefore, hypothesized that sFn also inhibits lymphocyte and interleukin-2-activated lymphocyte (LAK) adherence and cytotoxicity against tumor cells. This study sought to identify the lymphocyte subset responsible for adherence and killing of A375 melanoma cells and whether sFn inhibited these parameters. Lymphocyte and LAK cell adherence and cytotoxicity, which was adherence dependent, were inhibited by preincubation with purified or plasma-derived sFn. The lymphocyte and LAK cell activities were primarily a result of CD8(+) MHC (major histocompatibility complex) unrestricted cytotoxic T cells. These results suggest that elevated levels of circulating sFn may be immunosuppressive and may reduce the efficacy of adoptive immunotherapies. PMID:18160582

Biggerstaff, John P; Weidow, Brandy; Dexheimer, Judith; Warnes, Gary; Vidosh, Jacqueline; Patel, Shonak; Newman, Michael; Patel, Pretesh

2008-04-01

164

Histamine type I (H/sub 1/) receptor radioligand binding studies on normal T cell subsets, B cells, and monocytes  

SciTech Connect

A single, specific binding site for (/sup 3/H)pyrilamine on normal human T helper, T suppressor, B cells, and monocytes was documented. The binding of the radioligand to its receptor is reversible with cold H/sub 1/ antagonist, saturates at 40 to 60 nM, and binding equilibrium is achieved in 2 to 4 min. Using a computer program (Ligand), the authors calculated the dissociation constants, binding capacities, and numbers of receptors per cell for each of the different cell types. Monocytes were found to have the highest affinity for (/sup 3/H)pyrilamine, followed by T helper cells, B cells and T suppressor cells (K/sub D/ = 44.6 +/- 49.4 nM). T suppressor cells were found to express the higher number of H/sub 1/ receptors per cell followed by B cells, T helper cells, and monocytes. The binding affinity for (/sup 3/H)pyrilamine increased over a 48-hr period, whereas the number of receptors per T cell was essentially unchanged. In contrast, T cells stimulated with Con A or PHA were shown to have a greater than fourfold increase in the number of receptors per cell, whereas the binding affinity for (/sup 3/H)pyrilamine decreased over the 48-hr period. Although the function of H/sub 1/ receptors on T cells, B cells, and monocytes has not been completely defined, this receptor has the potential of playing an important role in the modulating the immune response.

Cameron, W.; Doyle, K.; Rocklin, R.E.

1986-03-15

165

Pivotal Roles of Monocytes/Macrophages in Stroke  

PubMed Central

Stroke is an important issue in public health due to its high rates both of morbidity and mortality, and high rate of disability. Hypertension, cardiovascular disease, arterial fibrillation, diabetes mellitus, smoking, and alcohol abuse are all risk factors for stroke. Clinical observations suggest that inflammation is also a direct risk factor for stroke. Patients with stroke have high levels of inflammatory cytokines in plasma, and immune cells, such as macrophages and T-lymphocytes, are noted within stroke lesions. These inflammatory events are considered as a result of stroke. However, recent studies show that plasma levels of inflammatory cytokines or soluble adhesion molecules are high in patients without stroke, and anti-inflammatory therapy is effective at reducing stroke incidence in not only animal models, but in humans as well. Statins have been shown to decrease the stroke incidence via anti-inflammatory effects that are both dependent and independent of their cholesterol-lowering effects. These reports suggest that inflammation might directly affect the onset of stroke. Microglial cells and blood-derived monocytes/macrophages play important roles in inflammation in both onset and aggravation of stroke lesions. We review the recent findings regarding the role of monocytes/macrophages in stroke.

Chiba, Tsuyoshi; Umegaki, Keizo

2013-01-01

166

TNF-? and TGF-? Counter-Regulate PD-L1 Expression on Monocytes in Systemic Lupus Erythematosus  

PubMed Central

Monocytes in patients with systemic lupus erythematosus (SLE) are hyperstimulatory for T lymphocytes. We previously found that the normal program for expression of a negative costimulatory molecule programmed death ligand-1 (PD-L1) is defective in SLE patients with active disease. Here, we investigated the mechanism for PD-L1 dysregulation on lupus monocytes. We found that PD-L1 expression on cultured SLE monocytes correlated with TNF-? expression. Exogenous TNF-? restored PD-L1 expression on lupus monocytes. Conversely, TGF-? inversely correlated with PD-L1 in SLE and suppressed expression of PD-L1 on healthy monocytes. Therefore, PD-L1 expression in monocytes is regulated by opposing actions of TNF-? and TGF-?. As PD-L1 functions to fine tune lymphocyte activation, dysregulation of cytokines resulting in reduced expression could lead to loss of peripheral T cell tolerance.

Ou, Jing-Ni; Wiedeman, Alice E.; Stevens, Anne M.

2012-01-01

167

Anti-CD20 B-cell depletion enhances monocyte reactivity in neuroimmunological disorders  

PubMed Central

Background Clinical trials evaluating anti-CD20-mediated B-cell depletion in multiple sclerosis (MS) and neuromyelitis optica (NMO) generated encouraging results. Our recent studies in the MS model experimental autoimmune encephalomyelitis (EAE) attributed clinical benefit to extinction of activated B-cells, but cautioned that depletion of naďve B-cells may be undesirable. We elucidated the regulatory role of un-activated B-cells in EAE and investigated whether anti-CD20 may collaterally diminish regulatory B-cell properties in treatment of neuroimmunological disorders. Methods Myelin oligodendrocyte glycoprotein (MOG) peptide-immunized C57Bl/6 mice were depleted of B-cells. Functional consequences for regulatory T-cells (Treg) and cytokine production of CD11b+ antigen presenting cells (APC) were assessed. Peripheral blood mononuclear cells from 22 patients receiving anti-CD20 and 23 untreated neuroimmunological patients were evaluated for frequencies of B-cells, T-cells and monocytes; monocytic reactivity was determined by TNF-production and expression of signalling lymphocytic activation molecule (SLAM). Results We observed that EAE-exacerbation upon depletion of un-activated B-cells closely correlated with an enhanced production of pro-inflammatory TNF by CD11b+ APC. Paralleling this pre-clinical finding, anti-CD20 treatment of human neuroimmunological disorders increased the relative frequency of monocytes and accentuated pro-inflammatory monocyte function; when reactivated ex vivo, a higher frequency of monocytes from B-cell depleted patients produced TNF and expressed the activation marker SLAM. Conclusions These data suggest that in neuroimmunological disorders, pro-inflammatory APC activity is controlled by a subset of B-cells which is eliminated concomitantly upon anti-CD20 treatment. While this observation does not conflict with the general concept of B-cell depletion in human autoimmunity, it implies that its safety and effectiveness may further advance by selectively targeting pathogenic B-cell function.

2011-01-01

168

Monocyte and macrophage heterogeneity in the heart  

PubMed Central

Monocytes and macrophages are innate immune cells that reside and accumulate in the healthy and injured heart. The cells and their subsets pursue distinct functions in steady state and disease, and their tenure may range between hours to months. Some subsets are highly inflammatory, while others support tissue repair. This review discusses current concepts of lineage relationships and systems’ cross talk, highlights open questions, and describes tools for studying monocyte and macrophage subsets in the murine and human heart.

Nahrendorf, Matthias; Swirski, Filip K.

2013-01-01

169

Monocyte and macrophage heterogeneity in the heart.  

PubMed

Monocytes and macrophages are innate immune cells that reside and accumulate in the healthy and injured heart. The cells and their subsets pursue distinct functions in steady-state and disease, and their tenure may range between hours and months. Some subsets are highly inflammatory, whereas others support tissue repair. This review discusses current concepts of lineage relationships and crosstalk of systems, highlights open questions, and describes tools for studying monocyte and macrophage subsets in the murine and human heart. PMID:23743228

Nahrendorf, Matthias; Swirski, Filip K

2013-06-01

170

Immunologic studies in two patients with persistent lymphocytic thyroiditis, thyrotoxicosis, and low radioactive iodine uptake  

SciTech Connect

Two patients with persistent lymphocytic thyroiditis and thyrotoxicosis were studied. Both patients presented with severe hyperthyroidism of nine months' duration and had nontender, small thyroid glands. Uptake of radioactive iodine (131I) was consistently low. Serum thyroxine and triiodothyronine levels remained elevated without remission until thyroidectomy. The serum thyroglobulin level was normal, but testing for microsomal antibody gave weakly positive results in one case. Thyroglobulin and thyroid stimulatory antibodies were not found. The ratio of helper to suppressor T cells was elevated in one case. Neither patient showed response to propranolol, prednisone, or iodine. Light microscopic and immunohistologic studies showed severe lymphocytic thyroiditis with formation of secondary lymphoid follicles. Lymphocytes were predominately T cells (OKT11-positive), primarily helper/inducer T cells (OKT4-positive). Hyperplastic nodules contained high immunoreactive thyroglobulin and thyroxine levels. Aberrant thymus was seen within the thyroid. These studies suggest the possibility of intrathyroidal stimulation and hydrolysis of thyroglobulin within thyroid cells and also support the hypothesis that T and B cell immunoregulatory defects are important in the pathogenesis of this disease.

Elliot, I.; Gupta, M.; Hostetter, A.; Sheeler, L.; Skillern, P.; Tubbs, R.

1984-08-01

171

In-111 tropolone complex for study of lymphocyte kinetics: Evidence for an induced defect in structure, function and viability  

SciTech Connect

The lipid soluble In-111 and tropolone complex (In-T) has been proposed as a desirable cell labeling moiety for in vivo studies. Its advantages over In-111 complexed to oxy/sup -/ or acetylacetonate are water solubility and efficient cell labeling in plasma. The authors examined the effect of In-T on lymphocyte integrity and function in preparation for studies of lymphocyte kinetics in traffic. At equal concentrations, both normal and lymphocytes from patients with chronic lymphocytic leukemia had cellular In-T uptake consistently 20% greater than that achieved with In-111 oxine. This desirable uptake led to studies of function and viability. Lymphocyte mitogenmediated blastogenic capability (an intrinsic lymphocyte function) was measured in vitro in ficoll-hypaque isolated normal lymphocytes with varying concentrations and intervals of exposure of In-T. Marked impairment of lymphocyte blastogenic responsiveness was seen with 3 different mitogens (concanavalin A, phytohemmagglutinin P, and pokeweed mitogen). Severe functional impairment was seen when cells were exposed to a In-T concentration of 10 ..mu..l/ml for 20 minutes; and a lesser effect was noted even at 10-minute incubation exposure. Cell viability, evaluated by trypan blue exclusion, was normal immediately following cell labeling, but rapidly and progressively failed to exclude (i.e. effective viability). Scanning electron microscopy demonstrated loss of the normal surface villous architecture within 36 hours of in vitro incubation following a 20-minute exposure. Thus, although In-T has attractive features, its effect on lymphocyte structure, function and viability eliminate it for in vivo studies in traffic kinetics.

Balaban, E.; Simon, T.R.; Kulkarni, P.; White, J.; Newton, M.; Frenkel, E.

1984-01-01

172

Bovine Lymphocytic Leukemia: Studies of Etiology, Pathogenesis, and Mode of Transmission. Progress Report No. 16, July 1975--July 1976.  

National Technical Information Service (NTIS)

We have consistently demonstrated viral like particles in mitogen stimulated lymphocyte cultures from leukemic cows and cows with a persistent lymphocytosis. Our electron microscopic studies of these particles have shown them to be similar to the known on...

D. K. Sorensen

1976-01-01

173

A Phase I/II Study of Etanercept and Rituximab in Patients with Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma  

PubMed Central

Rituximab has modest activity in relapsed Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) but is associated with TNF-? release that can cause CLL proliferation and inhibit apoptosis. We examined whether disruption of TNF-? by etanercept improves response to rituximab in CLL. Eligible patients had previously treated CLL with performance status 0–3. Patients received etanercept 25 mg subcutaneously twice weekly (weeks 1–5) and rituximab 375 mg/m2 intravenously thrice weekly (weeks 2–5) using a phase I/II design. Primary endpoints were response and toxicity. The 36 enrolled patients had a median of 2 prior treatments; 50% were fludarabine-refractory, and 22% had del(17p13.1). Of the 34 response-evaluable patients, ten (29%) responded, including 9 partial responses and 1 complete remission. Response was not affected by prior rituximab nor fludarabine-refractory status, but no patients with del(17p13.1) responded. Median PFS for responders was 9.0 months (range 1–43). Ten patients have had treatment-free intervals exceeding 12 months, including four who have remained untreated for 32, 43, 46 and 56 months. Adverse events were mild, including mild infusion reactions, transient cytopenias and grade 3 infections in 14%. The combination of etanercept and thrice weekly rituximab produces durable remissions in non-del(17p13.1) CLL patients and is well tolerated.

Woyach, Jennifer A; Lin, Thomas S; Lucas, Margaret S; Heerema, Nyla; Moran, Mollie E.; Cheney, Carolyn; Lucas, David M.; Wei, Lai; Caligiuri, Michael A.; Byrd, John C.

2014-01-01

174

Studies on the differentiation of T lymphocytes in sheep. II. Two monoclonal antibodies that recognize all ovine T lymphocytes.  

PubMed Central

Two mouse monoclonal cytotoxic antibodies (ST-1a and ST-1b) recognize an antigen present on the large majority of thymocytes and all T cells in the periphery, but not B cells or other haemopoietic cells in sheep. Examination of frozen sections of various fetal tissues revealed that the cells expressing this antigen first appeared in the thymus, and these cells markedly increase in numbers in the peripheral lymphoid tissues after mid-gestation. Large accumulations of positive cells were located in the paracortex of lymph nodes, the periarteriolar lymphoid sheath of the spleen, and interfollicular areas of jejunal Peyer's patches, all of which are known to be T-dependent areas. Treatment of lymphocytes with ST-1a and complement resulted in the abrogation of T-proliferative responses, but the response to a B-cell mitogen, lipopolysaccharide, was not reduced. Neither ST-1a nor ST-1b cross-reacted to lymphocytes obtained from other species of animals (man, monkey, mouse, rat, guinea-pig, chicken, frog, pig, horse, goat and cattle). Based on these findings, it was concluded that the expression of the antigen recognized by ST-1a and ST-1b is restricted to the T-cell lineage of sheep, and that all ovine T cells express this antigen. Furthermore, ST-1a and ST-1b were determined to recognize the same antigen by reciprocal blocking experiments. Images Figure 3

Beya, M F; Miyasaka, M; Dudler, L; Ezaki, T; Trnka, Z

1986-01-01

175

A study on binding of suspended nodal lymphocytes to high endothelial venules in sections of frozen rat lymph nodes.  

PubMed Central

Live lymphocytes were previously shown to bind selectively to endothelial cells (HEV cells) of the high endothelial venules (HEVs) in sections of frozen lymph nodes. This study examines aspects of the assay that have so far not been considered or which have been incompletely addressed. It was found that bound lymphocytes form a cytoplasmic veil, and that about half of them form small groups in which they are linked together by cytoplasmic bridges. It was also found that at least 83% of the lymphocytes bind to HEV walls, but very unevenly, and that 5% also bind to medullary venules. In addition, 31% of the lymphocytes were estimated to bind to the abluminal face of HEV cells and probably to tissue lymphocytes present in subendothelial spaces or in perivascular channels (spaces). This would reflect cell interactions occurring, in vivo, between HEV cells and/or subendothelial lymphocytes. It is suggested that antigen specificity of lymphocyte retention by HEV cells accounts for the uneven binding to HEVs. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 Fig. 11 Fig. 12 Fig. 13 Fig. 14 Fig. 15 Fig. 17 Fig. 18 Fig. 19 Fig. 20 Fig. 21 Fig. 22 Fig. 23

Sainte-Marie, G; Peng, F S

1995-01-01

176

Combined cytogenotoxic effects of bee venom and bleomycin on rat lymphocytes: an in vitro study.  

PubMed

This study was carried out to determine the cytotoxic and genotoxic effects of bee venom (BV) and/or the chemotherapeutic agent bleomycin (BLM) on healthy isolated rat lymphocytes utilizing morphometric and molecular techniques. Using the Ficoll-Histopaque density gradient centrifugation technique, lymphocytes were isolated, divided into groups, and subjected to BV and/or BLM at incubation medium concentrations of 10 or 20? ? g/mL respectively for 24 and 72?hrs. An MTT assay and fluorescent microscopy examinations were used to assess the cytotoxic effects. To determine the predominant type of BV and/or BLM-induced cell death, LDH release assay was employed beside quantitative expression analyses of the apoptosis-related genes (Caspase-3 and Bcl-2). The genotoxic effects of the tested compounds were evaluated via DNA fragmentation assay. The results of these assays demonstrated that BV potentiates BLM-induced cytotoxicity through increased LDH release and diminished cell viability. Nevertheless, BV significantly inhibited the BLM-induced DNA damage. The results verify that BV significantly attenuates the genotoxic effects of BLM on noncancerous isolated rat lymphocytes but does not diminish BLM cytotoxicity. PMID:24822179

Abd-Elhakim, Yasmina M; Khalil, Samah R; Awad, Ashraf; Al-Ayadhi, Laila Y

2014-01-01

177

Combined Cytogenotoxic Effects of Bee Venom and Bleomycin on Rat Lymphocytes: An In Vitro Study  

PubMed Central

This study was carried out to determine the cytotoxic and genotoxic effects of bee venom (BV) and/or the chemotherapeutic agent bleomycin (BLM) on healthy isolated rat lymphocytes utilizing morphometric and molecular techniques. Using the Ficoll-Histopaque density gradient centrifugation technique, lymphocytes were isolated, divided into groups, and subjected to BV and/or BLM at incubation medium concentrations of 10 or 20??g/mL respectively for 24 and 72?hrs. An MTT assay and fluorescent microscopy examinations were used to assess the cytotoxic effects. To determine the predominant type of BV and/or BLM-induced cell death, LDH release assay was employed beside quantitative expression analyses of the apoptosis-related genes (Caspase-3 and Bcl-2). The genotoxic effects of the tested compounds were evaluated via DNA fragmentation assay. The results of these assays demonstrated that BV potentiates BLM-induced cytotoxicity through increased LDH release and diminished cell viability. Nevertheless, BV significantly inhibited the BLM-induced DNA damage. The results verify that BV significantly attenuates the genotoxic effects of BLM on noncancerous isolated rat lymphocytes but does not diminish BLM cytotoxicity.

Abd-Elhakim, Yasmina M.; Khalil, Samah R.; Awad, Ashraf; AL-Ayadhi, Laila Y.

2014-01-01

178

Glatiramer acetate treatment effects on gene expression in monocytes of multiple sclerosis patients  

PubMed Central

Background Glatiramer acetate (GA) is a mixture of synthetic peptides used in the treatment of patients with relapsing-remitting multiple sclerosis (RRMS). The aim of this study was to investigate the effects of GA therapy on the gene expression of monocytes. Methods Monocytes were isolated from the peripheral blood of eight RRMS patients. The blood was obtained longitudinally before the start of GA therapy as well as after one day, one week, one month and two months. Gene expression was measured at the mRNA level by microarrays. Results More than 400 genes were identified as up-regulated or down-regulated in the course of therapy, and we analyzed their biological functions and regulatory interactions. Many of those genes are known to regulate lymphocyte activation and proliferation, but only a subset of genes was repeatedly differentially expressed at different time points during treatment. Conclusions Overall, the observed gene regulatory effects of GA on monocytes were modest and not stable over time. However, our study revealed several genes that are worthy of investigation in future studies on the molecular mechanisms of GA therapy.

2013-01-01

179

Monocytic HLA DR antigens in schizophrenic patients.  

PubMed

A genetic association of specific human leukocyte antigens (HLA) DR genes and schizophrenia has recently been shown. These HLA play a fundamental role in the control of immune responses. Furthermore infectious agents have been proposed to be involved in the pathogenesis of schizophrenia. In this study we investigated the rate of HLA DR positive monocytes in schizophrenic patients compared to controls with a special focus on the adaption to in vitro stimulation with toll-like receptor ligands. Patients with schizophrenia and matched controls were included. For each individual, we evaluated the rate of HLA DR positive monocytes (either incubated at 37 °C or after stimulation with lipopolysaccharide or Poly I:C). We found a significantly higher percentage of schizophrenic patients with elevated HLA DR positive cells (p=0.045) as compared to controls. The adjustment rate from baseline levels of monocytic HLA DR positive cells to stimulation with Poly I:C was significantly lower in schizophrenic patients (p=0.038). The increased monocytic HLA DR in schizophrenic patients and the maladjustment of their monocytic HLA DR levels to an infectious stimulus might be a sign for a disturbed monocytic immune balance in schizophrenic individuals. PMID:21964165

Krause, Daniela; Wagner, Jenny; Matz, Judith; Weidinger, Elif; Obermeier, Michael; Riedel, Michael; Gruber, Rudolf; Schwarz, Markus; Mueller, Norbert

2012-01-01

180

Human Lymphocyte Apoptosis after Exposure to Influenza A Virus  

PubMed Central

Infection of humans with influenza A virus (IAV) results in a severe transient leukopenia. The goal of these studies was to analyze possible mechanisms behind this IAV-induced leukopenia with emphasis on the potential induction of apoptosis of lymphocytes by the virus. Analysis of lymphocyte subpopulations after exposure to IAV showed that a portion of CD3+, CD4+, CD8+, and CD19+ lymphocytes became apoptotic (terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling positive). The percentage of cells that are infected was shown to be less than the percentage of apoptotic cells, suggesting that direct effects of cell infection by the virus cannot account fully for the high level of cell death. Removal of monocytes-macrophages after IAV exposure reduced the percent of lymphocytes that were apoptotic. Treatment of virus-exposed cultures with anti-tumor necrosis factor alpha did not reduce the percentage of lymphocytes that were apoptotic. In virus-exposed cultures treated with anti-FasL antibody, recombinant soluble human Fas, Ac-DEVD-CHO (caspase-3 inhibitor), or Z-VAD-FMK (general caspase inhibitor), apoptosis and production of the active form of caspase-3 was reduced. The apoptotic cells were Fas-high-density cells while the nonapoptotic cells expressed a low density of Fas. The present studies showed that Fas-FasL signaling plays a major role in the induction of apoptosis in lymphocytes after exposure to IAV. Since the host response to influenza virus commonly results in recovery from the infection, with residual disease uncommon, lymphocyte apoptosis likely represents a part of an overall beneficial immune response but could be a possible mechanism of disease pathogenesis.

Nichols, Joan E.; Niles, Jean A.; Roberts, Norbert J.

2001-01-01

181

Role of the ERK Pathway for Oxidant-Induced Parthanatos in Human Lymphocytes  

PubMed Central

Reactive oxygen species (ROS) are formed by myeloid cells as a defense strategy against microorganisms. ROS however also trigger poly(ADP-ribose) polymerase 1- (PARP-1) dependent cell death (parthanatos) in adjacent lymphocytes, which has been forwarded as a mechanism of immune escape in several forms of cancer. The present study assessed the role of mitogen-activated protein kinases (MAPKs), in particular the extracellular signal-regulated kinase (ERK), in ROS-induced signal transduction leading to lymphocyte parthanatos. We report that inhibitors of ERK1/2 phosphorylation upheld natural killer (NK) cell-mediated cytotoxicity under conditions of oxidative stress and rescued NK cells and CD8+ T lymphocytes from cell death induced by ROS-producing monocytes. ERK1/2 phosphorylation inhibition also protected lymphocytes from cell death induced by exogenous hydrogen peroxide (H2O2) and from ROS generated by xanthine oxidase or glucose oxidase. Phosphorylation of ERK1/2 was observed in lymphocytes shortly after exposure to ROS. ROS-generating myeloid cells and exogenous H2O2 triggered PARP 1-dependent accumulation of poly ADP-ribose (PAR), which was prevented by ERK pathway inhibitors. ERK1/2 phosphorylation was induced by ROS independently of PARP-1. Our findings are suggestive of a role for ERK1/2 in ROS-induced lymphocyte parthanatos, and that the ERK axis may provide a therapeutic target for the protection of lymphocytes against oxidative stress.

Akhiani, Ali A.; Werlenius, Olle; Aurelius, Johan; Movitz, Charlotta; Martner, Anna; Hellstrand, Kristoffer; Thoren, Fredrik B.

2014-01-01

182

Efficient generation of dendritic cells from alveolar and pleural macrophages as well as blood monocytes in patients with lung cancer.  

PubMed

In this study, we investigated the generation of dendritic cells (DCs) from blood monocytes and mature macrophages from untreated primary lung cancer patients. Blood monocytes were separated by adherence from blood mononuclear cells (MNC) from ten lung cancer patients and ten control subjects, and cultured for 7 days in medium with granulocyte/macrophage colony-stimulating factor (GM-CSF) plus interleukin (IL-) 4. In all cases examined, DCs with typical characteristics were obtained even in lung cancer patients after 7 days culture with these cytokines, and there was no significant difference in phenotype and stimulatory activity in allogeneic lymphocyte proliferation between DCs derived from monocytes from lung cancer patients and those from control subjects. Next, we examined whether alveolar and pleural macrophages in malignant pleural effusion separated by magnetic beads could differentiate to immunostimulatory DCs. Conventional culture conditions with GM-CSF and IL-4 did not induce efficient numbers of DCs from mature macrophages, whereas the addition of tumor necrosis factor-alpha (TNF-alpha) to GM-CSF and IL-4 effectively contributed to generate DCs. These findings suggest that both mature macrophages and blood monocytes from lung cancer patients could differentiate to DCs, and might be a useful source of DCs for immunotherapy. PMID:11679178

Suzuki, Y; Yanagawa, H; Nishioka, Y; Nishimura, N; Takeuchi, E; Sone, S

2001-11-01

183

Clinical and immunological evaluation of primary splenic irradiation in chronic lymphocytic leukemia: a study of 24 cases  

Microsoft Academic Search

Little is known about the effects of primary splenic irradiation (SI) in B-cell chronic lymphocytic leukemia (B-CLL) on subpopulations of lymphocytes, immunoglobulins, and the induction of autoantibodies against erythrocytes and platelets. Twenty-four untreated patients with B-CLL were studied prospectively. One patient was excluded from analysis because of intercurrent death. Of the remaining 23 patients, 7 were female and 16 were

W. N. K. A. van Mook; M. M. F. Fickers; T. A. M. Verschueren

2001-01-01

184

Human Brucellosis Is Characterized by an Intense Th1 Profile Associated with a Defective Monocyte Function?  

PubMed Central

In animal models, a defective Th1 response appears to be critical in the pathogenesis of brucellosis, but the Th1 response in human brucellosis patients remains partially undefined. Peripheral blood from 24 brucellosis patients was studied before and 45 days after antibiotherapy. Twenty-four sex- and age-matched healthy donors were analyzed in parallel. Significantly increased levels of interleukin 1? (IL-1?), IL-2, IL-4, IL-6, IL-12p40, gamma interferon (IFN-?), and tumor necrosis factor alpha (TNF-?), but not of IL-10, in serum and/or significantly increased percentages of samples with detectable levels of these cytokines, measured by enzyme-linked immunosorbent assays (ELISA), were found for untreated brucellosis patients, but these levels were reduced and/or normalized after treatment. Flow cytometry studies showed that the intracytoplasmic expression of IFN-?, IL-2, and TNF-?, but not that of IL-4, by phorbol myristate-activated CD4+ CD3+ and CD8+ CD3+ T lymphocytes was significantly increased in untreated brucellosis patients and was also partially normalized after antibiotherapy. The percentage of phagocytic cells, the mean phagocytic activity per cell, and the phagocytic indices for monocytes at baseline were defective and had only partially reverted at follow-up. T lymphocytes from untreated brucellosis patients are activated in vivo and show Th1 cytokine production polarization, with strikingly high serum IFN-? levels. In spite of this Th1 environment, we found deficient effector phagocytic activity in peripheral blood monocytes.

Rodriguez-Zapata, Manuel; Matias, Marlene J.; Prieto, Alfredo; Jonde, Marco A.; Monserrat, Jorge; Sanchez, Lorenzo; Reyes, Eduardo; De la Hera, Antonio; Alvarez-Mon, Melchor

2010-01-01

185

Substance P - Neurokinin-1 Receptor Interaction Upregulates Monocyte Tissue Factor  

PubMed Central

Monocytes play an important role in hemostasis. In this study, the prothrombotic effects of the neuropeptide substance P (SP) on human monocytes through neurokinin-1 receptor (NK1-R) were characterized. SP upregulated monocyte tissue factor (TF), the major coagulation cascade stimulator, in a concentration and time dependent manner. Specific inhibition of NK1-R completely blocked TF expression. Monocytes stimulated by SP released cytokines and chemokines. When monocytes were stimulated with cytokines or chemokines, TF was expressed by the cytokines (GM-CSF, IFN-? and TNF-?). Cytokines may play a major role in the mechanism of SP induced monocyte TF expression. NK1-R antagonists (NK1-RA) may have a role in developing novel therapeutic approaches to patients vulnerable to vaso-occlusive disorders.

Khan, Mohammad M; Douglas, Steven D; Benton, Tami D

2011-01-01

186

Monocytes can be induced to express lymphatic phenotypes.  

PubMed

Although it has been recently shown that monocytes can transdifferentiate into blood vascular endothelial cells which are involved in angiogenesis, little attention has been paid to their potential to transdifferentiate into lymphatic endothelial cells. Therefore, we examined this question in our study. We first stimulated monocytes with either fibronectin (FN), VEGF-C, TNF-alpha, LPS, or IL-3 for 24h. Then we examined the expression of several markers of lymphatic endothelium and found that the monocytes expressed specific lymphatic endothelial markers, LYVE-1, Podoplanin, and Prox-1, but not common endothelial markers vWF or eNOS. Next, monocytes were incubated in endothelial growth medium with FN and VEGF-C for 6d. These monocytes were also found to express LYVE-1, Podoplanin and Prox-1, but not vWF or eNOS. Our results indicate that monocytes in vitro can be easily induced to present lymphatic phenotypes in an inflammatory environment. PMID:21949973

Changming, W; Xin, L; Hua, T; Shikun, W; Qiong, X; Zhigeng, Z; Xueying, W

2011-06-01

187

Industrial Genotoxicology Group collaborative trial to investigate cell cycle parameters in human lymphocyte cytogenetics studies.  

PubMed

Human lymphocyte cultures have been used for many years for assessing the in vitro clastogenic potential of test substances. In these assays the harvest time should be based on the cell cycle time in order to ensure that cells are sampled at an appropriate time for the detection of clastogenic effects. The sources of variation in the cell cycle time in routine cytogenetic assays have not been well studied. Consequently 13 laboratories, all members of the Industrial Genotoxicology Group, participated in a collaborative study to measure the variation in cell cycle time in cultured human peripheral blood lymphocytes under various conditions. The study was performed in two phases, spaced 6 months apart. The average generation time (AGT) was measured by the incorporation of bromodeoxyuridine. Very similar AGTs were found in the presence and absence of S9 mix. The mean AGT (mean of four donors) in each laboratory varied from 11.2 to 17.1 h, indicating there is significant variability in cell cycle times of human peripheral blood lymphocytes between laboratories. There was greater variation between laboratories than within laboratories. A comparison of AGT values at 72 h performed in experiments at least 6 months apart indicated good reproducibility in most laboratories. The study indicates that a 24 h post-treatment harvest may result in the analysis of very few first division cells unless very significant cell cycle delay is induced by the test substance. It was also found that a post-harvest time equivalent to 1.5 cell cycles will result in an approximately equal mixture of first and second division cells and therefore should by suitable for assessing both the induction of chromosome aberrations and polyploidy. PMID:9175642

Henderson, L; Jones, E; Brooks, T; Chételat, A; Ciliutti, P; Freemantle, M; Howard, C A; Mackay, J; Phillips, B; Riley, S; Roberts, C; Wotton, A K; van de Waart, E J

1997-05-01

188

Defects in Mitochondrial Clearance Predispose Human Monocytes to Interleukin-1? Hypersecretion  

PubMed Central

Most hereditary periodic fever syndromes are mediated by deregulated IL-1? secretion. The generation of mature IL-1? requires two signals: one that induces synthesis of inflammasome components and substrates and a second that activates inflammasomes. The mechanisms that mediate autoinflammation in mevalonate kinase deficiency, a periodic fever disease characterized by a block in isoprenoid biosynthesis, are poorly understood. In studying the effects of isoprenoid shortage on IL-1 ? generation, we identified a new inflammasome activation signal that originates from defects in autophagy. We find that hypersecretion of IL-1? and IL-18 requires reactive oxygen species and is associated with an oxidized redox status of monocytes but not lymphocytes. IL-1? hypersecretion by monocytes involves decreased mitochondrial stability, release of mitochondrial content into the cytosol and attenuated autophagosomal degradation. Defective autophagy, as established by ATG7 knockdown, results in prolonged cytosolic retention of damaged mitochondria and increased IL-1? secretion. Finally, activation of autophagy in healthy but not mevalonate kinase deficiency patient cells reduces IL-1? secretion. Together, these results indicate that defective autophagy can prime monocytes for mitochondria-mediated NLRP3 inflammasome activation, thereby contributing to hypersecretion of IL-1? in mevalonate kinase deficiency.

van der Burgh, Robert; Nijhuis, Lotte; Pervolaraki, Kalliopi; Compeer, Ewoud B.; Jongeneel, Lieneke H.; van Gijn, Marielle; Coffer, Paul J.; Murphy, Michael P.; Mastroberardino, Pier G.; Frenkel, Joost; Boes, Marianne

2014-01-01

189

Glucocorticoid suppression of human lymphocyte DNA synthesis. Influence of phytohemagglutinin concentration  

SciTech Connect

Glucocorticoids have been shown to suppress lectin-stimulated lymphocyte DNA synthesis in some studies, whereas in other studies, the hormones have had little effect. We have found that the position on the PHA dose-response curve that is studied is the most important determinant of whether cortisol inhibits /sup 3/H-thymidine incorporation into lymphocyte DNA. The proportion of monocytes in culture also influenced the cortisol effect, but it was quantitatively less important than PHA concentration. Cortisol (5 nM to 100 ..mu..M) had little effect on blastogenesis or thymidine incorporation into DNA in cultures that contained both a high concentration (14% +- 2 (S.E.)) of monocytes and a concentration of PHA (0.6 to 1.2 ..mu..g/ml) that produced maximal stimulation of mitogenesis. When monocytes were reduced from 14 to 1.4%, cortisol (5 ..mu..M) caused a 30% reduction in thymidine incorporation in cultures stimulated by 0.6 to 1.2 ..mu..g/ml PHA. Much greater cortisol suppression of thymidine incorporation occurred if the concentration of PHA was reduced. For example, reduction of the PHA concentration from 1.2 to 0.075 ..mu..g/ml resulted in an increase in suppression by 5 ..mu..M cortisol from 5 to 90% even in the presence of 14% monocytes. These data indicate that the suppressive effects of glucocorticoids on blastogenesis and thymidine incorporation in vitro depend principally on the concentration of PHA used to stimulate blastogenesis and secondarily on the proportion of monocytes in the culture system.

Segel, G.B.; Lukacher, A.; Gordon, B.R.; Lichtman, M.A.

1980-04-01

190

Interaction between turkey monocytes and avian Chlamydia psittaci in the presence of Mycoplasma sp.: the importance of nitric oxide  

Microsoft Academic Search

The interaction between Chlamydia psittaci and turkey monocytes was studied in vitro. Purified monocytes were inoculated with C. psittaci, in the presence or absence of Mycoplasma hyorhinis. Whereas turkey monocytes produced high amounts of nitric oxide (NO) following the inoculation with M. hyorhinis, inoculation with C. psittaci did not induce NO production in these phagocytes. The monocytes strongly supported chlamydial

Anne Van Nerom; Richard Ducatelle; Gerard Charlier; Freddy Haesebrouck

2000-01-01

191

CD44 clustering is involved in monocyte differentiation.  

PubMed

Differentiation of monocytes into macrophages is an important process under physiological and pathological conditions, but the underlying mechanism of monocyte differentiation is not completely clear. Some adhesion molecules have been reported to play an important role in cell differentiation. CD44 is an important adhesion molecule that mediates cell-cell and cell-matrix interaction, and participates in a wide variety of cellular functions. As CD44 has been reported to show different activated states between monocytes and macrophages, we propose that CD44 may be involved in monocyte differentiation. In this study, we explored the role of CD44 in monocyte differentiation and further studied the mechanisms that were involved in. THP-1 cells (human monocytic leukemia cell line) were induced with phorbol 12-myristate 13-acetate (PMA) to establish the model of monocyte differentiation in vitro. It was found that CD44 expression and binding capacity to hyaluronic acid were increased significantly, and the distribution of CD44 was converted into clusters during differentiation. The PMA-induced CD44 clustering and CD44 high expression were suppressed by blocking CD44, which resulted in the inhibition of CD14 expression. PMA-induced phosphorylation of ERK1/2 signal was also suppressed by blocking CD44. Our results suggested that CD44 was involved in monocyte differentiation. The mechanisms of monocyte differentiation following CD44 activation may include CD44 high expression and clustering which in turn lead to phosphorylation of ERK1/2. PMID:24850301

Zhang, Guoliang; Zhang, Huizhen; Liu, Yiwen; He, Yiqing; Wang, Wenjuan; Du, Yan; Yang, Cuixia; Gao, Feng

2014-07-01

192

Herpes simplex virus antigens directly activate NK cells via TLR2, thus facilitating their presentation to CD4 T lymphocytes.  

PubMed

NK cells infiltrate human herpetic lesions, but their role has been underexplored. HSV can stimulate innate immune responses via surface TLR2, which is expressed on monocyte-derived dendritic cells (DCs) and NK cells. In this study, UV-inactivated HSV1/2 and immunodominant HSV2 glycoprotein D peptides conjugated to the TLR2 agonist dipalmitoyl-S-glyceryl cysteine stimulated CD4 T lymphocyte IFN-? responses within PBMCs or in coculture with monocyte-derived DCs. NK cells contributed markedly to the PBMC responses. Furthermore, NK cells alone were activated directly by both Ags, also upregulating HLA-DR and HLA-DQ and then they activated autologous CD4 T lymphocytes. Using Transwells, Ag-stimulated NK cells and CD4 T lymphocytes were shown to interact through both cell-to-cell contact and cytokines, differing in relative importance in different donors. A distinct immunological synapse between Ag-stimulated NK cells and CD4 T lymphocytes was observed, indicating the significance of their cell-to-cell contact. A large proportion (57%) of NK cells was also in contact with CD4 T lymphocytes in the dermal infiltrate of human recurrent herpetic lesions. Thus, NK cells stimulated by TLR2-activating HSV Ags can present Ag alone or augment the role of DCs in vitro and perhaps in herpetic lesions or draining lymph nodes. In addition to DCs, NK cells should be considered as targets for adjuvants during HSV vaccine development. PMID:22467654

Kim, Min; Osborne, Naomi R; Zeng, Weiguang; Donaghy, Heather; McKinnon, Kay; Jackson, David C; Cunningham, Anthony L

2012-05-01

193

Lack of autologous mixed lymphocyte reaction in patients with chronic lymphocytic leukemia: evidence for autoreactive T-cell dysfunction not correlated with phenotype, karyotype, or clinical status  

SciTech Connect

In the present study, there was a complete lack of autologous MLR between responding T cells or T subsets and unirradiated or irradiated leukemic B cells or monocytes in all 20 patients with CLL, regardless of disease status, stage, phenotype, or karyotype of the disease. The stimulating capacity of unirradiated CLL B cells and CLL monocytes or irradiated CLL B cells was significantly depressed as compared to that of respective normal B cells and monocytes in allogeneic MLR. The responding capacity of CLL T cells was also variably lower than that of normal T cells against unirradiated or irradiated normal allogeneic B cells and monocytes. The depressed allogeneic MLR between CLL B cells or CLL monocytes and normal T cells described in the present study could be explained on the basis of a defect in the stimulating antigens of leukemic B cells or monocytes. The decreased allogeneic MLR of CLL T cells might simply be explained by a defect in the responsiveness of T lymphocytes from patients with CLL. However, these speculations do not adequately explain the complete lack of autologous MLR in these patients. When irradiated CLL B cells or irradiated CLL T cells were cocultured with normal T cells and irradiated normal B cells, it was found that there was no suppressor cell activity of CLL B cells or CLL T cells on normal autologous MLR. Our data suggest that the absence or dysfunction of autoreactive T cells within the Tnon-gamma subset account for the lack of autologous MLR in patients with CLL. The possible significance of the autologous MLR, its relationship to in vivo immunoregulatory mechanisms, and the possible role of breakdown of autoimmunoregulation in the oncogenic process of certain lymphoproliferative and autoimmune diseases in man are discussed.

Han, T.; Bloom, M.L.; Dadey, B.; Bennett, G.; Minowada, J.; Sandberg, A.A.; Ozer, H.

1982-11-01

194

Selective expansion of the monocytic lineage directed by bacterial infection.  

PubMed

CCR2-mediated recruitment of Ly6C(high) monocytes is essential for defense against a range of microbial pathogens. Although our understanding of monocyte trafficking to inflammatory sites is increasing, how innate immune inflammation influences monocyte development and maturation during microbial infection remains undefined. Herein, we demonstrate that infection with the intracellular bacterial pathogen Listeria monocytogenes specifically and selectively promotes monopoiesis. Systemic infection with virulent L. monocytogenes induces marked proliferation of bone marrow monocyte precursors and results in depletion of myeloid progenitors. Proliferation of monocyte precursors correlates with the intensity of systemic infection and is unaffected by the density of monocytes in the bone marrow. Although MyD88/Trif-mediated signaling is not required for early emigration of the mature monocyte population from the bone marrow, replenishment of monocyte populations depends on MyD88/Trif. Our studies demonstrate that TLR-mediated signals play an essential role in the maintenance of monocyte homeostasis during systemic bacterial infection. PMID:19596996

Serbina, Natalya V; Hohl, Tobias M; Cherny, Mathew; Pamer, Eric G

2009-08-01

195

[Immunohistochemical studies of paraneoplastic subacute sensory neuropathy--an analysis of antineuronal antibody and infiltrated lymphocytes].  

PubMed

In order to clarify the pathogenesis of paraneoplastic syndrome, immunohistochemical studies were performed in a patient with subacute sensory neuropathy secondary to a small cell lung cancer. The case was a 73-year-old ex-farmer, whose chief complaints were pins and needles sensation of distal limbs and gait difficulty. After 6 weeks prodromata of pain in the upper limbs and numbness in all the limbs, he became unable to stand up without assistance. Neurological examinations on admission revealed marked sensory disturbances with glove and stocking type hypalgesia to pin prick and the loss of position and vibration senses in the distal extremities. His deep tendon reflexes also decreased in all the limbs. A chest X-ray showed a mass in the left upper lung field. A transbronchial lung biopsy of the mass revealed a small cell carcinoma. He was treated with anti-cancer drugs and radiation but he died of pneumonia after 8 months illness. Autopsy revealed a marked demyelination of the entire posterior column of the spinal cord. Dorsal root ganglia were infiltrated by lymphocytes with significant neuronal loss. Immunohistochemically, most of the infiltrated cells around the neurons were classified as CD8+ with fewer CD4+ lymphocytes. No B-lymphocytes were detected in the ganglia. The HLA-ABC and HLA-DR positive cells were found only among the satellite cells, not in the neurons. The serum and CSF from the patient were immunohistologically reacted with the nuclei and cytoplasm of all neurons of human as well as of rats, indicating the presence of anti-Hu type antineuronal antibody in the patient's CSF as well as serum.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1327606

Yoshioka, A; Ueda, Y; Sakai, K; Negami, T; Hirose, G

1992-04-01

196

Monocyte chemoattractant protein-1 serum levels in ovarian cancer patients  

Microsoft Academic Search

The chemokine monocyte chemoattractant protein (MCP)-1 is an important mediator of monocyte infiltration in various solid tumours of epithelial origin. The aim of the present study was to evaluate the role of MCP-1 in the natural history of ovarian cancer and to determine its value as differentiation marker and prognostic marker regarding disease free and overall survival. This retrospective study

L Hefler; C Tempfer; G Heinze; K Mayerhofer; G Breitenecker; S Leodolter; A Reinthaller; C Kainz

1999-01-01

197

Studies on Non-H-2 Linked Lymphocyte Activating Determinants. I. Description of the Cell Type Bearing the MLS Product.  

National Technical Information Service (NTIS)

The non-H-2 linked, lymphocyte activating determinants (LADs), which are coded by the minor (histocompatibility) lymphocyte stimulating locus (Mls), were detected on B lymphocytes, but not on immunoglobulin (Ig) negative or on theta positive T lymphocytes...

A. Ahmed I. Scher A. H. Smith K. W. Sell

1976-01-01

198

Human monocytes respond to extracellular cAMP through A2A and A2B adenosine receptors.  

PubMed

In this study, we test the hypothesis that cAMP, acting as an extracellular mediator, affects the physiology and function of human myeloid cells. The cAMP is a second messenger recognized as a universal regulator of several cellular functions in different organisms. Many studies have shown that extracellular cAMP exerts regulatory functions, acting as first mediator in multiple tissues. However, the impact of extracellular cAMP on cells of the immune system has not been fully investigated. We found that human monocytes exposed to extracellular cAMP exhibit higher expression of CD14 and lower amount of MHC class I and class II molecules. When cAMP-treated monocytes are exposed to proinflammatory stimuli, they exhibit an increased production of IL-6 and IL-10 and a lower amount of TNF-? and IL-12 compared with control cells, resembling the features of the alternative-activated macrophages or M2 macrophages. In addition, we show that extracellular cAMP affects monocyte differentiation into DCs, promoting the induction of cells displaying an activated, macrophage-like phenotype with reduced capacity of polarized, naive CD4(+) T cells into IFN-?-producing lymphocytes compared with control cells. The effects of extracellular cAMP on monocytes are mediated by CD73 ecto-5'-nucleotidase and A2A and A2B adenosine receptors, as selective antagonists could reverse its effects. Of note, the expression of CD73 molecules has been found on the membrane of a small population of CD14(+)CD16(+) monocytes. These findings suggest that an extracellular cAMP-adenosine pathway is active in cells of the immune systems. PMID:24652540

Sciaraffia, Ester; Riccomi, Antonella; Lindstedt, Ragnar; Gesa, Valentina; Cirelli, Elisa; Patrizio, Mario; De Magistris, Maria Teresa; Vendetti, Silvia

2014-07-01

199

1 alpha,25-Dihydroxyvitamin D3 receptors in human thymic and tonsillar lymphocytes.  

PubMed

In vitro activated human peripheral blood lymphocytes possess the receptor protein for 1 alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3). In the present study we have examined whether activated lymphocytes that occur in vivo in human thymuses and tonsils also possess receptors for 1,25(OH)2D3. Freshly isolated lymphocyte preparations, from five separate surgical specimens of thymus and tonsil, were depleted of monocytes and examined, before and after fractionation on a density gradient of Percoll, for [3H] 1,25(OH)2D3 binding by means of sucrose density gradient sedimentation, by saturation analysis of the binding, and by DNA-cellulose chromatography. The state of activation of the lymphocyte preparations was determined using [3H] thymidine incorporation, DNA and RNA quantitation (using acridine orange), and by determining the presence or absence of markers of activation (interleukin-2 receptor, transferrin receptor, and HLA-DR molecules). In both the thymic and the tonsillar lymphocyte preparations we detected a 1,25(OH)2D3-binding molecule possessing sedimentation coefficient of 3.3 S and dissociation constant of 10(-10) M as well as DNA binding capability. In thymic lymphocytes, the 1,25(OH)2D3 receptor concentration correlated positively with the number of lymphocytes expressing the transferrin receptor (r = 0.84; p less than 0.05). In addition, in both thymic and tonsillar lymphocytes the concentration of 1,25(OH)2D3 receptors correlated positively with the number of cells in the G1a phase of the cell cycle (r = 0.79, p less than 0.01, and r = 0.88, p less than 0.001 for thymic and tonsillar lymphocytes, respectively). In contrast, the 1,25(OH)2D3 receptor concentration in these preparations did not correlate with the rate of cell proliferation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2843004

Provvedini, D M; Rulot, C M; Sobol, R E; Tsoukas, C D; Manolagas, S C

1987-06-01

200

Studies of T-lymphocytes in preleukemic disorders and acute nonlymphocytic leukemia: in vitro radiosensitivity, mitogenic responsiveness, colony formation, and enumeration of lymphocytic subpopulations  

Microsoft Academic Search

Tritiated thymidine incorporation in a whole blood lymphocyte stimulation test (LST) and lymphocyte colony formation (CFU-L) from whole blood were measured following in vitro x-irradiation. Lymphocytes from patients with myelodysplastic disorders, acute nonlymphocytic leukemia, and patients at increased risk for leukemia because of their primary disease and\\/or cytotoxic therapy were found to be significantly more sensitive to in vitro x-irradiation

S. J. Knox; B. R. Greenberg; R. W. Anderson; L. S. Rosenblatt

1983-01-01

201

Ten year follow up study of lymphocytic gastritis: further evidence on Helicobacter pylori as a cause of lymphocytic gastritis and corpus gastritis.  

PubMed Central

AIMS--To examine the course of lymphocytic gastritis and its relation to Helicobacter pylori (H pylori) infection in a 10 year follow up. METHODS--Ninety six patients were originally examined for dyspepsia in 1981. Gastroscopies with stepwise biopsies were performed on all the patients initially and after an interval of 10 years. RESULTS--Nine per cent of the patients (9/96) had features of lymphocytic gastritis in gastric biopsy at the first examination, and 12.5% (12/96) at the second examination; 7/9 patients (78%) had persistent lymphocytic gastritis during the follow up; in two the diagnostic features of lymphocytic gastritis had disappeared, and five had a new diagnosis of lymphocytic gastritis at the second examination. At the second examination 9/12 lymphocytic gastritis patients (75%) were H pylori positive histologically, while all had specific antibodies to H pylori. The lymphocytic gastritis patients had higher grades of gastritis (p = 0.009), neutrophilic and eosinophilic granulocytes, mononuclear inflammatory cells, and foveolar hyperplasia in the corpus mucosa, but smaller numbers of H pylori, than the H pylori positive patients without lymphocytic gastritis. The appearance of lymphocytic gastritis during the 10 year interval was associated with increases in the grades of corpus gastritis and neutrophilic granulocytes (p = 0.043 for both). During the follow up, the patients with lymphocytic gastritis, but not the H pylori positive patients without lymphocytic gastritis, appeared to have a significant increase in the grade of intestinal metaplasia in the corpus mucosa (p = 0.043). CONCLUSIONS--In some patients H pylori may cause a gastritis that predominates in the corpus and is associated with an increase in the intraepithelial lymphocyte count. This form of gastritis may cause progression of intestinal metaplasia. Images

Niemela, S; Karttunen, T; Kerola, T; Karttunen, R

1995-01-01

202

Pregnancy and Preeclampsia Affect Monocyte Subsets in Humans and Rats  

PubMed Central

Introduction Both nonclassical and intermediate monocytes have been implicated in different inflammatory conditions. We hypothesized that these monocytes would increase during pregnancy, a condition associated with generalized activation of inflammatory responses and that they would increase even more during preeclampsia, in which inflammatory responses are further stimulated. In the present study we investigated changes in monocyte subsets during healthy pregnancy and preeclampsia in humans and rats. Methods Blood monocyte subsets of nonpregnant, preeclamptic and healthy pregnant women were identified with CD14 and CD16. In nonpregnant and pregnant rats, blood monocytes were identified with CD172a and CD43, as well as in rats infused with adenosine triphosphate (ATP), a pro-inflammatory stimulus known to induce preeclampsia-like symptoms. Total and CD206-positive macrophages were quantified in placentas of these animals. Results Lower percentages of classical monocytes were found in pregnant women (91%–[83–98%]) compared to nonpregnant women (94%–[90–98%]) and even less in preeclamptic patients (90%–[61–92%]). In contrast, the percentage of combined nonclassical/intermediate monocytes was higher in pregnant women (8.5%–[2.3–16.6%] vs. 5.6%–[1.9–9.5%]) and even higher in preeclamptic patients (9.9%–[7.8–38.7%]), which was caused by a selective increase of intermediate monocytes. In rats, we also found lower percentages of classical monocytes and higher percentages of nonclassical monocytes in pregnant versus nonpregnant rats. ATP infusion increased the percentage of nonclassical monocytes in pregnant rats even further but not in nonpregnant rats. These nonclassical monocytes showed a more activated phenotype in pregnant ATP-infused rats only. Mesometrial triangles of ATP-infused rats had less CD206-positive macrophages as compared to those of saline-infused rats. Conclusion The higher percentage of nonclassical/intermediate monocytes found in pregnancy and preeclampsia confirms their association with inflammatory responses. The observation that ATP stimulated numbers/activation of nonclassical monocytes in pregnant rats only, suggests that nonclassical monocytes are specifically altered in pregnancy and may play a role in the pathophysiology of preeclampsia.

Borghuis, Theo; Klok, Pieter A.; Groen, Bart; Bolt, Annemarie; de Vos, Paul; van Pampus, Maria G.; Wong, Tsz Y.; van Goor, Harry; Bakker, Winston W.; Faas, Marijke M.

2012-01-01

203

Distinct responses of human monocyte subsets to Aspergillus fumigatus conidia.  

PubMed

Aspergillus fumigatus is an environmental fungus that causes life-threatening infections in neutropenic patients. In the absence of intact innate immunity, inhaled A. fumigatus spores (conidia) germinate in the lung, forming hyphae that invade blood vessels and disseminate to other tissues. Although macrophages and neutrophils are postulated to provide defense against invasive fungal infection, animal models and human studies suggest that circulating monocytes also contribute to antifungal immunity. Although human monocyte subsets, defined as either CD14(+)CD16(-) or CD14(+)CD16(+), have been extensively characterized, their respective roles during fungal infection remain undefined. We isolated CD14(+)CD16(-) and CD14(+)CD16(+) monocytes from healthy allogeneic hematopoietic stem cell transplantation donors and compared their ability to phagocytose and inhibit A. fumigatus conidia. Both monocyte subsets efficiently phagocytose conidia, but only CD14(+)CD16(-) monocytes inhibit conidial germination yet secrete little TNF. In contrast CD14(+)CD16(+) do not inhibit conidial germination and secrete large amounts of TNF. Although CD14(+)CD16(-) and CD14(+)CD16(+) monocytes differ in their response to dormant conidia, responses are similar if conidia are already germinated at the time of monocyte uptake. Our study demonstrates that functional CD14(+)CD16(-) and CD14(+)CD16(+) monocytes can be isolated from allogeneic hematopoietic stem cell transplantation donors and that these subsets differ in their response to A. fumigatus conidia. PMID:19635902

Serbina, Natalya V; Cherny, Mathew; Shi, Chao; Bleau, Sharon A; Collins, Nancy H; Young, James W; Pamer, Eric G

2009-08-15

204

Monocyte Subsets in Schistosomiasis Patients with Periportal Fibrosis  

PubMed Central

A major issue with Schistosoma mansoni infection is the development of periportal fibrosis, which is predominantly caused by the host immune response to egg antigens. Experimental studies have pointed to the participation of monocytes in the pathogenesis of liver fibrosis. The aim of this study was to characterize the subsets of monocytes in individuals with different degrees of periportal fibrosis secondary to schistosomiasis. Monocytes were classified into classical (CD14++CD16?), intermediate (CD14++CD16+), and nonclassical (CD14+CD16++). The expressions of monocyte markers and cytokines were assessed using flow cytometry. The frequency of classical monocytes was higher than the other subsets. The expression of HLA-DR, IL-6, TNF-?, and TGF-? was higher in monocytes from individuals with moderate to severe fibrosis as compared to other groups. Although no differences were observed in receptors expression (IL-4R and IL-10R) between groups of patients, the expression of IL-12 was lower in monocytes from individuals with moderate to severe fibrosis, suggesting a protective role of this cytokine in the development of fibrosis. Our data support the hypothesis that the three different monocyte populations participate in the immunopathogenesis of periportal fibrosis, since they express high levels of proinflammatory and profibrotic cytokines and low levels of regulatory markers.

Fernandes, Jamille Souza; Araujo, Maria Ilma; Lopes, Diego Mota; de Souza, Robson da Paixao; Carvalho, Edgar M.; Cardoso, Luciana Santos

2014-01-01

205

In Vitro and in Vivo Activation of B-Lymphocytes: A Flow Cytometric Study of Chromatin Structure Employing 7-AminoactinomycinD1  

Microsoft Academic Search

The chromatin structure of a diploid precursor B-cell line (REH), in >>\\/fro-stimulatednormal B-lymphocytes, and reactive and malignant lymph node B-lymphocytes was studied by staining formaldehyde-fixed, permeabilized cells with the DNA-specific ftuorophore 7-aminoactino- mycin D (7-AMD) and measuring single-cell fluorescence by flow cytom- etry. Resting peripheral blood B- and T-lymphocytes (Go cells) bound low amounts of 7-AMD (7-AMIr phenotype), while (.,

Trond Stokke; Harald Holte; Harald B. Steen

206

Aphase 1 and pharmacodynamic study of depsipeptide (FK228) in chronic lymphocytic leukemia and acute myeloid leukemia  

Microsoft Academic Search

Preclinical studies with the histone deacetylase (HDAC) inhibitor depsipep- tide (FK228) in chronic lymphocytic leuke- mia (CLL) and acute myeloid leukemia (AML) have demonstrated that it effec- tively induces apoptosis at concentra- tions at which HDAC inhibition occurs. We initiated a minimum effective pharma- cologic dose study of depsipeptide, tar- geting an in vivo dose at which acetyla- tion of

John C. Byrd; Guido Marcucci; Mark R. Parthun; Jim J. Xiao; Rebecca B. Klisovic; Mollie Moran; Thomas S. Lin; Shujun Liu; Amy R. Sklenar; Melanie E. Davis; David M. Lucas; Beth Fischer; Roshini Shank; Sooraj L. Tejaswi; Philip Binkley; John Wright; Kenneth K. Chan; Michael R. Grever

2005-01-01

207

The study of different chromosomal aberrations, CD38 and ZAP-70 in chronic lymphocytic leukemia patients.  

PubMed

Chronic lymphocytic leukemia (CLL) follows an extremely variable clinical course with overall survival times ranging from months to decades. The clinical staging systems do not allow one to predict if and at what rate there will be disease progression in an individual patient diagnosed with early stage disease. There has been intensive work on clinical and biological factors of potential prognostic relevance that may add to the classic assessment provided by the staging systems. Among these are: Laboratory parameters reflecting the tumor burden or disease activity such as lymphocyte count, lactate dehydrogenase (LDH) elevation, bone marrow infiltration pattern or lymphocyte doubling time (LDT), serum markers such as soluble CD23, beta2-microglobulin (beta2-MG) or thymidine kinase (TK), and genetic markers of tumor cells such as genomic aberrations, the mutation status of the variable segments of immunoglobulin heavy chain genes (VH), or surrogate markers for these factors (CD38, ZAP-70, LPL). Thirty patients were included in our study, the investigation included CD38 expression, ZAP-70 expression, and interphase Fluorescence In Situ Hybridization (FISH) for the detection of trisomy 12, del 13q14.3, del 17p13, and del 11q22.3. Our results showed positive statistical significant correlation between ZAP-70 expression and CD38 expression with some of the chromosomal aberrations encompassing bad prognosis as ATM and p53. Also CD38 expression was positively correlated with trisomy 12 and p53 deletions. Chromosomal aberrations were found to be present in 76.6% of our patients with 13q deletion as the most frequent abnormality in our patients (46.7%), followed by trisomy 12 (36.7%), then ATM and p53 deletion (26.7%) each. Another interesting finding in our study is the fact that 100% of the ZAP-70 positive patients were of bad prognosis, 58.3% of the CD38 positive cases, 81.8% of the positive trisomy 12 cases, 100% of the ATM deletion, 62.5% of the p53 deletion, and 64.3% of the 13q- cases were also of bad prognosis, which indicates that ZAP-70, trisomy 12, and ATM deletion are powerful indicators of prognosis. We conclude that FISH for the detection of the most important chromosomal aberrations in CLL is an important laboratory parameter that is recommended for assessment and correlation with simultaneous evaluation of ZAP-70 and CD38 expression which could help in the prediction of outcome of CLL patients. PMID:23082473

Hassab, A H; Elbordiny, M M; Elghandour, A H; Sorour, A F; Swelem, R S

2011-01-01

208

Genome-Wide Association Study Identifies Single Nucleotide Polymorphism in DYRK1A Associated with Replication of HIV-1 in Monocyte-Derived Macrophages  

PubMed Central

Background HIV-1 infected macrophages play an important role in rendering resting T cells permissive for infection, in spreading HIV-1 to T cells, and in the pathogenesis of AIDS dementia. During highly active anti-retroviral treatment (HAART), macrophages keep producing virus because tissue penetration of antiretrovirals is suboptimal and the efficacy of some is reduced. Thus, to cure HIV-1 infection with antiretrovirals we will also need to efficiently inhibit viral replication in macrophages. The majority of the current drugs block the action of viral enzymes, whereas there is an abundance of yet unidentified host factors that could be targeted. We here present results from a genome-wide association study identifying novel genetic polymorphisms that affect in vitro HIV-1 replication in macrophages. Methodology/Principal Findings Monocyte-derived macrophages from 393 blood donors were infected with HIV-1 and viral replication was determined using Gag p24 antigen levels. Genomic DNA from individuals with macrophages that had relatively low (n?=?96) or high (n?=?96) p24 production was used for SNP genotyping with the Illumina 610 Quad beadchip. A total of 494,656 SNPs that passed quality control were tested for association with HIV-1 replication in macrophages, using linear regression. We found a strong association between in vitro HIV-1 replication in monocyte-derived macrophages and SNP rs12483205 in DYRK1A (p?=?2.16×10?5). While the association was not genome-wide significant (p<1×10?7), we could replicate this association using monocyte-derived macrophages from an independent group of 31 individuals (p?=?0.0034). Combined analysis of the initial and replication cohort increased the strength of the association (p?=?4.84×10?6). In addition, we found this SNP to be associated with HIV-1 disease progression in vivo in two independent cohort studies (p?=?0.035 and p?=?0.0048). Conclusions/Significance These findings suggest that the kinase DYRK1A is involved in the replication of HIV-1, in vitro in macrophages as well as in vivo.

Bol, Sebastiaan M.; Moerland, Perry D.; Limou, Sophie; van Remmerden, Yvonne; Coulonges, Cedric; van Manen, Danielle; Herbeck, Joshua T.; Fellay, Jacques; Sieberer, Margit; Sietzema, Jantine G.; van 't Slot, Ruben; Martinson, Jeremy; Zagury, Jean-Francois; Schuitemaker, Hanneke; van 't Wout, Angelique B.

2011-01-01

209

Distinct immunologic effects of different intravenous iron preparations on monocytes  

PubMed Central

Background Iron deficiency contributes to anaemia in patients with chronic kidney disease. I.v. iron is therefore widely used for anaemia treatment, although it may induce oxidative stress and activate monocytes. Different i.v. iron preparations are available, but interestingly their substance-specific immunologic effects are poorly studied. Methods We analysed the effect of iron sucrose, ferric carboxymaltose, iron isomaltoside 1000, low-molecular-weight iron dextran and ferumoxytol on classical, intermediate and nonclassical monocyte biology. We therefore stimulated in vitro mature monocytes and haematopoietic CD34+ stem cells during their differentiation into monocytes with different concentrations (0.133, 0.266, 0.533 mg/mL) of i.v. iron preparations. Alterations of monocyte subset distribution, expression of surface markers (CD86, CCR5, CX3CR1), as well as production of pro-inflammatory cytokines (TNF-?, IL-1?) and reactive oxygen species were measured using flow cytometry. Additionally, we analysed phagocytosis and antigen presentation capacity. Results We found specific immunologic effects after stimulation with iron sucrose which were not induced by the other iron preparations. Iron sucrose activated monocyte subsets leading to significantly increased CD86 expression. Simultaneously CD16 and CX3CR1 expression and monocytic phagocytosis capacity were decreased. Additionally, differentiation of monocytes from haematopoietic CD34+ stem cells was almost completely abolished after stimulation with iron sucrose. Conclusions Our findings demonstrate that specific immunologic effects of distinct i.v. iron preparations exist. The clinical relevance of these findings requires further investigation.

Fell, Lisa H.; Zawada, Adam M.; Rogacev, Kyrill S.; Seiler, Sarah; Fliser, Danilo; Heine, Gunnar H.

2014-01-01

210

Prevalence of interferon type I signature in CD14 monocytes of patients with Sj?gren's syndrome and association with disease activity and BAFF gene expression  

PubMed Central

Objective To determine the prevalence of upregulation of interferon (IFN) type I inducible genes, the so called ‘IFN type I signature’, in CD14 monocytes in 69 patients with primary Sjögren's syndrome (pSS) and 44 healthy controls (HC) and correlate it with disease manifestations and expression of B cell activating factor (BAFF). Methods Expression of IFI44L, IFI44, IFIT3, LY6E and MX1 was measured using real time quantitative PCR in monocytes. Expression values were used to calculate IFN type I scores for each subject. pSS patients positive for the IFN type I signature (IFN score?10) and patients negative for the signature (IFN score<10) were then compared for clinical disease manifestations and BAFF expression. A bioassay using a monocytic cell line was performed to study whether BAFF mRNA expression was inducible by IFN type I activity in serum of patients with pSS. Results An IFN type I signature was present in 55% of patients with pSS compared with 4.5% of HC. Patients with the IFN type I signature showed: (a) higher EULAR Sjögren's Syndrome Disease Activity Index scores; higher anti-Ro52, anti-Ro60 and anti-La autoantibodies; higher rheumatoid factor; higher serum IgG; lower C3, lower absolute lymphocyte and neutrophil counts; (b)higher BAFF gene expression in monocytes. In addition, serum of signature-positive patients induced BAFF gene expression in monocytes. Conclusions The monocyte IFN type I signature identifies a subgroup of patients with pSS with a higher clinical disease activity together with higher BAFF mRNA expression. Such patients might benefit from treatment blocking IFN type I production or activity.

Brkic, Zana; Maria, Naomi I; van Helden-Meeuwsen, Cornelia G; van de Merwe, Joop P; van Daele, Paul L; Dalm, Virgil A; Wildenberg, Manon E; Beumer, Wouter; Drexhage, Hemmo A; Versnel, Marjan A

2013-01-01

211

Correlations between Lymphocytes, Mid-Cell Fractions and Granulocytes with Human Blood Characteristics Using Low Power He-Ne Laser Radiation  

Microsoft Academic Search

In this study, the subpopulations of human blood parameters including lymphocytes, the mid-cell fractions (eosinophils, basophils, and monocytes), and granulocytes were determined by electronic sizing in the Health Centre of Universiti Sains Malaysia. These parameters have been correlated with human blood characteristics such as age, gender, ethnicity, and blood types; before and after irradiation with 0.95 mW He-Ne laser (lambda

Hend A. A. Houssein; M. S. Jaafar; R. M. Ramli; N. E. Ismail; A. L. Ahmad; M. Y. Bermakai

2010-01-01

212

Correlations between Lymphocytes, Mid-Cell Fractions and Granulocytes with Human Blood Characteristics Using Low Power He-Ne Laser Radiation  

Microsoft Academic Search

In this study, the subpopulations of human blood parameters including lymphocytes, the mid-cell fractions (eosinophils, basophils, and monocytes), and granulocytes were determined by electronic sizing in the Health Centre of Universiti Sains Malaysia. These parameters have been correlated with human blood characteristics such as age, gender, ethnicity, and blood types; before and after irradiation with 0.95 mW He-Ne laser (?

Hend A. A. Houssein; M. S. Jaafar; R. M. Ramli; N. E. Ismail; A. L. Ahmad; M. Y. Bermakai

2010-01-01

213

Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia.  

PubMed

Genome-wide association studies (GWAS) have previously identified 13 loci associated with risk of chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL). To identify additional CLL susceptibility loci, we conducted the largest meta-analysis for CLL thus far, including four GWAS with a total of 3,100 individuals with CLL (cases) and 7,667 controls. In the meta-analysis, we identified ten independent associated SNPs in nine new loci at 10q23.31 (ACTA2 or FAS (ACTA2/FAS), P=1.22×10(-14)), 18q21.33 (BCL2, P=7.76×10(-11)), 11p15.5 (C11orf21, P=2.15×10(-10)), 4q25 (LEF1, P=4.24×10(-10)), 2q33.1 (CASP10 or CASP8 (CASP10/CASP8), P=2.50×10(-9)), 9p21.3 (CDKN2B-AS1, P=1.27×10(-8)), 18q21.32 (PMAIP1, P=2.51×10(-8)), 15q15.1 (BMF, P=2.71×10(-10)) and 2p22.2 (QPCT, P=1.68×10(-8)), as well as an independent signal at an established locus (2q13, ACOXL, P=2.08×10(-18)). We also found evidence for two additional promising loci below genome-wide significance at 8q22.3 (ODF1, P=5.40×10(-8)) and 5p15.33 (TERT, P=1.92×10(-7)). Although further studies are required, the proximity of several of these loci to genes involved in apoptosis suggests a plausible underlying biological mechanism. PMID:23770605

Berndt, Sonja I; Skibola, Christine F; Joseph, Vijai; Camp, Nicola J; Nieters, Alexandra; Wang, Zhaoming; Cozen, Wendy; Monnereau, Alain; Wang, Sophia S; Kelly, Rachel S; Lan, Qing; Teras, Lauren R; Chatterjee, Nilanjan; Chung, Charles C; Yeager, Meredith; Brooks-Wilson, Angela R; Hartge, Patricia; Purdue, Mark P; Birmann, Brenda M; Armstrong, Bruce K; Cocco, Pierluigi; Zhang, Yawei; Severi, Gianluca; Zeleniuch-Jacquotte, Anne; Lawrence, Charles; Burdette, Laurie; Yuenger, Jeffrey; Hutchinson, Amy; Jacobs, Kevin B; Call, Timothy G; Shanafelt, Tait D; Novak, Anne J; Kay, Neil E; Liebow, Mark; Wang, Alice H; Smedby, Karin E; Adami, Hans-Olov; Melbye, Mads; Glimelius, Bengt; Chang, Ellen T; Glenn, Martha; Curtin, Karen; Cannon-Albright, Lisa A; Jones, Brandt; Diver, W Ryan; Link, Brian K; Weiner, George J; Conde, Lucia; Bracci, Paige M; Riby, Jacques; Holly, Elizabeth A; Smith, Martyn T; Jackson, Rebecca D; Tinker, Lesley F; Benavente, Yolanda; Becker, Nikolaus; Boffetta, Paolo; Brennan, Paul; Foretova, Lenka; Maynadie, Marc; McKay, James; Staines, Anthony; Rabe, Kari G; Achenbach, Sara J; Vachon, Celine M; Goldin, Lynn R; Strom, Sara S; Lanasa, Mark C; Spector, Logan G; Leis, Jose F; Cunningham, Julie M; Weinberg, J Brice; Morrison, Vicki A; Caporaso, Neil E; Norman, Aaron D; Linet, Martha S; De Roos, Anneclaire J; Morton, Lindsay M; Severson, Richard K; Riboli, Elio; Vineis, Paolo; Kaaks, Rudolph; Trichopoulos, Dimitrios; Masala, Giovanna; Weiderpass, Elisabete; Chirlaque, María-Dolores; Vermeulen, Roel C H; Travis, Ruth C; Giles, Graham G; Albanes, Demetrius; Virtamo, Jarmo; Weinstein, Stephanie; Clavel, Jacqueline; Zheng, Tongzhang; Holford, Theodore R; Offit, Kenneth; Zelenetz, Andrew; Klein, Robert J; Spinelli, John J; Bertrand, Kimberly A; Laden, Francine; Giovannucci, Edward; Kraft, Peter; Kricker, Anne; Turner, Jenny; Vajdic, Claire M; Ennas, Maria Grazia; Ferri, Giovanni M; Miligi, Lucia; Liang, Liming; Sampson, Joshua; Crouch, Simon; Park, Ju-Hyun; North, Kari E; Cox, Angela; Snowden, John A; Wright, Josh; Carracedo, Angel; Lopez-Otin, Carlos; Bea, Silvia; Salaverria, Itziar; Martin-Garcia, David; Campo, Elias; Fraumeni, Joseph F; de Sanjose, Silvia; Hjalgrim, Henrik; Cerhan, James R; Chanock, Stephen J; Rothman, Nathaniel; Slager, Susan L

2013-08-01

214

In vivo Validation of Signaling Pathways Regulating Human Monocyte Chemotaxis  

PubMed Central

Identification of novel signal transduction pathways regulating monocyte chemotaxis can indicate unique targets for preventive therapies for treatment of chronic inflammatory diseases. To aid in this endeavor we report conditions for optimal transfection of primary human monocytes coupled with a new model system for assessing their chemotactic activity in vivo. This method can be used as a tool to identify the relevant signal transduction pathways regulating human monocyte chemotaxis to MCP-1 in the complex in vivo environment that were previously identified to regulate chemotaxis in vitro. MCP-1-dependent chemotaxis of monocytes is studied in an adoptive transfer model where human monocytes transfected with mutant cDNAs are transferred to mice followed by initiation of peritonitis. Harvesting peritoneal cells at 24 h diminishes the contribution of immunologic responses to the cross-species transfer. Validation of relevant regulatory molecules in vivo is critical for understanding the most relevant therapeutic targets for drug development.

Bhattacharjee, Ashish; Mishra, Ravi S.; Feldman, Gerald M.; Cathcart, Martha K.

2008-01-01

215

Inflammatory and Immune Cell Function in Psoriasis: II. Monocyte Function, Lymphokine Production  

Microsoft Academic Search

We have previously confirmed that subjects with psoriasis have a alteration of cell-mediated immune responses. We now report a possible in vitro corollary; the amount of lymphokine (lymphocyte-derived chemotactic factor) released by both antigen-stimulated and control lymphocytes is decreased in psoriatic subjects; 61% of similar values for normal subjects. Monocyte migration to complement-derived chemotactic factors is reported to directly correlate

Gerald G. Krueger; Warren W. Jederberg; Bruce E. Ogden; Don L. Reese

1978-01-01

216

Cytoskeleton changes and impaired motility of monocytes at modelled low gravity  

Microsoft Academic Search

Summary.  Investigations performed in space have shown that gravity changes affect important cellular mechanisms like proliferation,\\u000a differentiation, genetic expression, cytoskeletal architecture, and motility in lymphocytes, monocytes, and other mammalian\\u000a cells. In particular, a dramatic depression of the mitogenic in vitro activation of human peripheral blood lymphocytes was\\u000a observed at low gravity. The hypothesis of the present work is that a reduced

M. A. Meloni; G. Galleri; P. Pippia; M. Cogoli-Greuter

2006-01-01

217

Human bladder uroepithelial cells synergize with monocytes to promote IL-10 synthesis and other cytokine responses to uropathogenic Escherichia coli.  

PubMed

Urinary tract infections are a major source of morbidity for women and the elderly, with Uropathogenic Escherichia coli (UPEC) being the most prevalent causative pathogen. Studies in recent years have defined a key anti-inflammatory role for Interleukin-10 (IL-10) in urinary tract infection mediated by UPEC and other uropathogens. We investigated the nature of the IL-10-producing interactions between UPEC and host cells by utilising a novel co-culture model that incorporated lymphocytes, mononuclear and uroepithelial cells in histotypic proportions. This co-culture model demonstrated synergistic IL-10 production effects between monocytes and uroepithelial cells following infection with UPEC. Membrane inserts were used to separate the monocyte and uroepithelial cell types during infection and revealed two synergistic IL-10 production effects based on contact-dependent and soluble interactions. Analysis of a comprehensive set of immunologically relevant biomarkers in monocyte-uroepithelial cell co-cultures highlighted that multiple cytokine, chemokine and signalling factors were also produced in a synergistic or antagonistic fashion. These results demonstrate that IL-10 responses to UPEC occur via multiple interactions between several cells types, implying a complex role for infection-related IL-10 during UTI. Development and application of the co-culture model described in this study is thus useful to define the degree of contact dependency of biomarker production to UPEC, and highlights the relevance of histotypic co-cultures in studying complex host-pathogen interactions. PMID:24155979

Duell, Benjamin L; Carey, Alison J; Dando, Samantha J; Schembri, Mark A; Ulett, Glen C

2013-01-01

218

Human Bladder Uroepithelial Cells Synergize with Monocytes to Promote IL-10 Synthesis and Other Cytokine Responses to Uropathogenic Escherichia coli  

PubMed Central

Urinary tract infections are a major source of morbidity for women and the elderly, with Uropathogenic Escherichia coli (UPEC) being the most prevalent causative pathogen. Studies in recent years have defined a key anti-inflammatory role for Interleukin-10 (IL-10) in urinary tract infection mediated by UPEC and other uropathogens. We investigated the nature of the IL-10-producing interactions between UPEC and host cells by utilising a novel co-culture model that incorporated lymphocytes, mononuclear and uroepithelial cells in histotypic proportions. This co-culture model demonstrated synergistic IL-10 production effects between monocytes and uroepithelial cells following infection with UPEC. Membrane inserts were used to separate the monocyte and uroepithelial cell types during infection and revealed two synergistic IL-10 production effects based on contact-dependent and soluble interactions. Analysis of a comprehensive set of immunologically relevant biomarkers in monocyte-uroepithelial cell co-cultures highlighted that multiple cytokine, chemokine and signalling factors were also produced in a synergistic or antagonistic fashion. These results demonstrate that IL-10 responses to UPEC occur via multiple interactions between several cells types, implying a complex role for infection-related IL-10 during UTI. Development and application of the co-culture model described in this study is thus useful to define the degree of contact dependency of biomarker production to UPEC, and highlights the relevance of histotypic co-cultures in studying complex host-pathogen interactions.

Duell, Benjamin L.; Carey, Alison J.; Dando, Samantha J.; Schembri, Mark A.; Ulett, Glen C.

2013-01-01

219

Detection of CD 14 on migrated monocytes by specific antibody: a possible quantification for blood monocyte chemotaxis.  

PubMed

In the present study we investigated the possibility to use antigen-antibody recognition for detection of monocyte chemotaxis in the 48-well microchamber assay. The described method is based on recognition of cell-specific antigenic determinants present on the migrated monocytes. After conventional 48-well chemotaxis, the migrated cells were incubated with an antibody against the monocyte surface marker CD14 (3C10 hybridoma). Subsequent incubation with enzyme-coupled antibodies and their substrate allowed the antigen and hence the migrated cells carrying this antigen, to be detected and measured in a microplate reader. Our results show that chemotaxis of normal blood monocytes towards the monocyte chemoattractants FMLP and MCP-1 could be detected with the anti-CD14 antibody 3C10 in combination with a horse-radish peroxidase coupled antibody, and that the optical density is a measure for cell number per well (positive correlation, r = 0.95). Incubation of monocytes with the applied chemoattractants FMLP and MCP-1 did not change the CD14 expression as was determined by FACScan analysis. Therefore we conclude that it is possible to use antibodies directed against antigenic determinants like CD14 to detect blood monocyte migration in a more objective way compared to subjective counting of cells on a filter. Eventually, this method can be valuable, especially for chemokine research since chemokines exert their effects on specific target cell populations. By varying the detection antibody, other cell populations besides monocytes may be quantified. PMID:8933153

Tekstra, J; Tuk, C W; Beelen, R H

1996-10-01

220

Monocyte-Plasmablast Crosstalk during Dengue.  

PubMed

Dengue virus infection induces a dramatic expansion of B cell plasmablasts. In this issue, Kwissa et al. (2014) begin with transcriptomic analysis and then integrate studies in human clinical samples, nonhuman primates, and coculture of primary human cells to identify a role for CD14(+)CD16(+) monocytes in generating plasmablast responses during dengue virus infection. PMID:25011103

Green, Angela M; Harris, Eva

2014-07-01

221

Enzymatic digestion of the milk protein ?-casein releases potent chemotactic peptide(s) for monocytes and macrophages  

PubMed Central

Proteins in the milk release biologically active peptides upon enzymatic digestion. In the present study, we report the identification of novel monocyte/macrophage chemotactic peptides derived from enzymatically digested bovine ?-casein, a casein family member that is a major constituent of the milk. ?-casein fragments generated by actinase E showed potent chemotactic activity for human and mouse monocytes/macrophages, but not neutrophils, T lymphocytes or dendritic cells. The fragment-induced migration of human monocytes was inhibited by pertussis toxin and was not desensitized by a variety of known chemoattractants, suggesting that the digests activate a unique G protein-coupled receptor(s). The digests were further fractionated and purified to yield 3 small peptides. One peptide Q1 designated as “?-casochemotide-1” with the amino acid sequence of YPVEP (f114-118 of ?-casein) induced high levels of macrophage chemotaxis. It also promoted calcium mobilization in macrophages, another indication of cell activation. Our study suggests that biologically active peptides released by actinase-digested milk ?-casein may promote innate host immune responses by inducing macrophage migration and activation.

Kitazawa, Haruki; Yonezawa, Kumiko; Tohno, Masanori; Shimosato, Takeshi; Kawai, Yasushi; Saito, Tadao; Wang, Ji Ming

2009-01-01

222

Monocyte count at diagnosis is a prognostic parameter in diffuse large B-cell lymphoma: results from a large multicenter study involving 1191 patients in the pre- and post-rituximab era  

PubMed Central

In this study we assessed the prognostic significance of absolute monocyte count and selected the best cut-off value at diagnosis in a large cohort of patients with diffuse large B-cell lymphoma. Data were retrieved for therapy-naďve patients with diffuse large B-cell lymphoma followed in Israel and Italy during 1993–2010. A final cohort of 1017 patients was analyzed with a median follow up of 48 months and a 5-year overall survival rate of 68%. The best absolute monocyte count cut-off level was 630/mm3 and the 5-year overall survival for patients with counts below this cut-off was 71%, whereas it was 59% for those with a count >630 mm3 (P=0.0002). Of the 1017 patients, 521 (51%) were treated with chemo-immunotherapy, and in this cohort, using multivariate analysis, elevated monocyte count retained a negative prognostic value even when adjusted for International Prognostic Index (HR1.54, P=0.009). This large study shows that a simple parameter such as absolute monocyte count (>630/mm3) can easily be used routinely in the evaluation of newly diagnosed diffuse large B-cell lymphoma to identify high-risk patients with a worse survival in the rituximab era.

Tadmor, Tamar; Bari, Alessia; Sacchi, Stefano; Marcheselli, Luigi; Liardo, Eliana Valentina; Avivi, Irit; Benyamini, Noam; Attias, Dina; Pozzi, Samantha; Cox, Maria Christina; Baldini, Luca; Brugiatelli, Maura; Federico, Massimo; Polliack, Aaron

2014-01-01

223

Effect of infection with BHV-1 on peripheral blood leukocytes and lymphocyte subpopulations in calves with subclinical BVD.  

PubMed

Bovine viral diarrhea virus (BVDV) and bovine herpesvirus-1 (BHV-1) are important cattle pathogens that induce a broad immunosuppression on cell-mediated immune response on its own participating in the bovine respiratory disease complex (BRDC). The aim of our study was to evaluate the quantitative changes in immunocompetent cells in healthy calves and calves with subclinical bovine viral diarrhea (BVD), both inoculated with BHV-1. Total leukocyte counts exhibited changes mainly in neutrophils and lymphocytes that can contribute to the BVDV immunosuppression, thus accounting for some of the intergroup differences. Monocytes did not display numerical changes in either group. Regarding lymphocyte subpopulations, even though CD4+ T lymphocytes and B cells were depleted around 4 dpi in both infected groups, the main difference observed between both groups was in CD8+ T cells which displayed an earlier depletion in BVDV inoculated calves that can promote a greater BHV-1 dissemination, thus aggravating the course of the disease. PMID:23541923

Molina, V; Risalde, M A; Sánchez-Cordón, P J; Pedrera, M; Romero-Palomo, F; Luzzago, C; Gómez-Villamandos, J C

2013-08-01

224

Increased Intracellular, Cell Surface, and Secreted Inducible Heat Shock Protein 70 Responses Are Triggered during the Monocyte to Dendritic Cell (DC) Transition by Cytokines Independently of Heat Stress and Infection and May Positively Regulate DC Growth  

PubMed Central

Physiologic triggers and functional consequences of endogenous heat shock protein (HSP) responses in dendritic cells (DC) are poorly defined. In this study, we show that even in the absence of heat stress and infection, a specific cohort of DC/proinflammatory cytokines (IL-4-IL-13/IL-6/GM-CSF) institutes an enhanced inducible (i)HSP70 intracellular and extracellular response in human monocyte-derived DC, especially during the monocyte to DC transition. Interestingly, whereas heat stress alone initiated an intracellular iHSP70 response in monocyte DC precursors, it did not promote cell surface or secreted iHSP70 responses, both of which were induced by cytokines independently of heat. The cytokine-induced iHSP70 response, which did not occur in lymphocytes, or monocytes-macrophages generated with M-CSF, was instituted within 48 h of cytokine exposure, and peaked upon commitment to DC growth at 72 h. Although a return to baseline levels was noted after this period, a distinct rise in iHSP70 occurred again during terminal DC maturation. Chemical inhibition of the iHSP70 response with either triptolide or KNK-437 was coupled with inhibition of DC differentiation and yielded cells displaying features of monocytes-macrophages. Exogenously supplied riHSP70 amplified events associated with cytokine-advanced DC differentiation/maturation, most notably the up-regulation of antiapoptotic proteins (Bcl-xL). Engaging the HSP receptor CD40 with CD40L produced identical results as extracellular riHSP70, and, moreover, an enhanced iHSP70 response. Thus, distinct iHSP70 and HSP receptor-mediated responses are triggered by cytokines irrespective of heat stress and infection in monocyte-derived DC and may function to positively regulate monocyte-derived DC, especially during critical periods of their growth.

Martin, Carla A.; Kurkowski, Danielle L.; Valentino, Alisa M.; Santiago-Schwarz, Frances

2011-01-01

225

Studies of immunomodulating actions of carotenoids. I. Effects of ??carotene and astaxanthin on murine lymphocyte functions and cell surface marker expression in in vitro culture system  

Microsoft Academic Search

The immunomodulating effects of carotenoids (??carotene and astaxanthin) on mouse lymphocytes were studied in in vitro culture system by use of assay for mitogen responses of spleen cells, thymocyte proliferation, interleukin 2 production, and antibody (Ab) production in vitro in response to sheep red blood cells. Changes of cell surface markers on spleen lymphocytes including la antigen (Ag), surface immunoglobulin,

Harumi Jyonouchi; Roberta J. Hill; Yoshifumi Tomita; Robert A. Good

1991-01-01

226

Variation in the Monocyte Proteome  

Microsoft Academic Search

We have determined the variability of the monocyte proteome and identified those proteins that demonstrate the greatest variation in the general control population. Monocytes were isolated from 18 healthy (9 male and 9 female) donors ages 18- 50 and with no known genetic or blood disorder. A combination of Ficoll-Paque PLUS density centrifugation of cells found in the buffy coat

ANITA HRYNIEWICZ-JANKOWSKA; PANKAJ K. CHOUDHARY; STEVEN R. GOODMAN

2007-01-01

227

Monocyte-selective transendothelial migration: dissection of the binding and transmigration phases by an in vitro assay  

PubMed Central

We describe a quantitative assay of transendothelial migration (TEM) that allows us to selectively study the interaction of monocytes with confluent human endothelial cell (HEC) monolayers. The HEC are grown on hydrated collagen gels; the monocytes need not be purified. 100% of monocytes transmigrated the monolayer within 1 h at 37 degrees C and accumulated in the subendothelial collagen; TEM of lymphocytes was not detected within this time. Migration of neutrophils from the same donor was much slower and incomplete, with only 14% of PMN transmigrating in 2 h. This rapid TEM occurs in the absence of exogenous chemoattractants, and HEC in this system do not express cytokine- inducible leukocyte adhesion molecules. A slight modification of the TEM assay allowed us to separate binding to the apical HEC surface from TEM. We found that tight apical surface binding was the rate-limiting step for TEM. Two-thirds of this binding and TEM could be blocked by a monoclonal antibody against the leukocyte beta 2 integrin chain CD18. This assay will allow us to dissect the mechanisms of both the binding and transmigration stages of diapedesis.

1992-01-01

228

Activation of human monocyte and natural killer cell-mediated tumour cell killing by two dialysable thymic factors.  

PubMed

Components of calf thymus extract dialysable under acid conditions contained two natural killer (NK) cytotoxicity-stimulating factors, CSFa and CSFb, which could be separated by ion exchange chromatography. NK cytotoxicity of human peripheral blood mononuclear cells (PBMC) against human K562 tumour cells was strongly enhanced after 72 h pre-incubation with the factors. The CSFa/b-specific stimulation of PBMC required the presence of monocytes. The cytotoxic effector cells activated during pre-incubation of PBMC with the CSF were identified as monocytes and as NK cells present in the fraction of large granular lymphocytes (LGL). Selective cell depletion studies with LGL-containing subpopulations (free of monocytes) allowed factor-specific discrimination of the activated LGL. Pre-incubation of PBMC with CSFa stimulated NK cytotoxicity of LGL (Leu 7+11-; T8-), whereas pre-incubation with CSFb resulted in stimulation of LGL (Leu 7+11-; T8+). The biological effects of CSFa and CSFb could be further distinguished by analysis of surface marker expression during incubation of PBMC. CSFb scarcely influenced T4 expression, but strongly enhanced the expression of T8 and that of transferrin receptor, whereas CSFa had no significant influence on the expression of these three surface markers. Both factors induced a drastic reduction of tumour take incidence or tumour development in mice when applied before and after tumour challenge. PMID:3726459

Hamprecht, K; Vötsch, W; Anderer, F A

1986-07-01

229

Anti-monocyte chemoattractant protein 1 gene therapy attenuates experimental chronic pancreatitis induced by dibutyltin dichloride in rats  

PubMed Central

Background: Monocyte chemoattractant protein 1 (MCP-1) is a member of the C-C chemokine family and exerts strong chemoattractant activity in monocytes, macrophages, and lymphocytes. Rat pancreatic fibrosis induced by dibutyltin dichloride (DBTC) is considered to be an appropriate chronic pancreatitis model histologically and enzymatically, as has demonstrated in a previous study. Aim: We examined the effect of human dominant negative inhibitor of MCP-1 (mutant MCP-1) on progression of chronic pancreatitis induced by DBTC in a rat model. Methods: We used the experimental model of chronic pancreatitis induced by DBTC in rats. Mutant MCP-1 or empty plasmid at a dose of 50 µg/body weight was administrated into rat thigh muscles on days 4, 11, and 18 after administration of DBTC. On days 14 and 28, we evaluated the effect of mutant MCP-1 morphologically and biochemically. Results: The mutant MCP-1 treated group inhibited early pancreatic inflammation and later pancreatic fibrosis histologically, and showed a decrease in serum MCP-1 concentration, intrapancreatic hydroxyproline, ?-smooth muscle actin, and an increase in intrapancreatic amylase and protein content compared with the empty plasmid treated group. The mutant MCP-1 group also inhibited intrapancreatic mRNA expression of cytokines and chemokines. Conclusions: : Our findings suggest that monocyte/macrophage recruitment and the systemic MCP-1 signal pathway contribute to progression of chronic pancreatitis, and that blockade of MCP-1 may suppress the development of pancreatic fibrosis.

Zhao, H F; Ito, T; Gibo, J; Kawabe, K; Oono, T; Kaku, T; Arita, Y; Zhao, Q W; Usui, M; Egashira, K; Nawata, H

2005-01-01

230

Isolation of porcine monocyte population: a simple and efficient method.  

PubMed

Monocytes are important mediators of inflammatory processes and are in the focus of immunological studies. While the preparation of human monocytes is widely established, little is published on the isolation of porcine monocytes for experimental studies. The aim of this study is to establish a cost efficient method of preparing and culturing porcine monocytes of considerable purity and reasonable yield. In our method, we combined and modified different protocols of human monocyte preparation. The blood of a single pig is harvested and treated with EDTA to prevent coagulation. Peripheral blood mononuclear cells are obtained by a density gradient centrifugation using a Bicoll gradient and monocytes are harvested by culturing on serum-treated culture flasks, rinsing and tapping. A high yield is obtained by constant cooling of flasks and tubes. The purity of the culture is evaluated by the expression of CD14, using flow cytometry. Using this method, we reached a purity of 92.6 % (± 3.06 %). With this procedure, we established a reliable method to prepare and cultivate porcine monocytes which can be performed cost effectively and does not require special equipment. PMID:23624769

Berg, Christin; Wilker, Sebastian; Roider, Johann; Klettner, Alexa

2013-09-01

231

Release of sFasL by Monocytes and Lympho- cytes Triggered by Betaglucan and Zymosan  

Microsoft Academic Search

Background: Polysaccharides have long been used as immune-modulators in various pathologic conditions including inflammation and solid malignancies. Objective: To evaluate the effects of Zymosan and Betaglucan on cytotoxic reactions in an effector- target conjugate system. Methods: Blood was obtained from 20 healthy subjects; pu- rified mononuclear leukocytes (monocytes and lymphocytes) were extracted and cul- tured as effector cells by a

Ziba Ghasemi; Babak Farrokhi; Farah Miraghasi; Ardalan Ejaz Ahmad; Nariman Mosaffa

2006-01-01

232

Inability of newborns' or pregnant women's monocytes to suppress pokeweed mitogen-induced responses  

SciTech Connect

Although an excess of human adult blood adherent cells inhibits the pokeweed mitogen- (PWM) induced normal adult lymphocyte proliferation and B cell maturation into immunoglobulin-containing cells (ICC), adherent cells collected from newborn infants or pregnant women at time of delivery were unable to exert a similar suppressor activity. After activation by Concanavalin A (Con A), newborns' and pregnant women's adherent cells acquired a suppressor activity comparable to that of control adult adherent cells. The adherent suppressor cell was shown to be radioresistant (3000 rad), indicating its probable monocytic orgin. Both monocyte-suppressor activities (MSA) observed in adulthood (spontaneously) and in the neonatal period (after activation) were dependent on prostaglandin E/sub 2/ (PGE/sub 2/) secretion, because they were abolished by indomethacin or a specific anti-PGE/sub 2/ anti-serum. Expression of MSA appeared to be under a negative regulation exerted by naturally occurring T suppressor lymphocytes present in the blood of newborns or pregnant women, because incubation of adult monocytes or Con A-activated newborn monocytes with newborns' or pregnant women's T lymphocytes resulted in a dramatic decrease of their MSA. These results strongly suggest that the lack of MSA in the neonatal period and in late pregnancy is a consequence of activation of T suppressor lymphocytes.

Durandy, A.; Fischer, A.; Griscelli, C.

1982-02-01

233

The human cytokine I-309 is a monocyte chemoattractant.  

PubMed Central

The human cytokine I-309 is a small glycoprotein secreted by activated T lymphocytes and structurally related to a number of inflammatory cytokines. To investigate the biological activities of I-309 protein, we produced a stable Chinese hamster ovary cell transfectant, CDI.10, which constitutively secretes I-309 protein into culture supernatant. Affinity chromatography on a heparin-Sepharose matrix followed by reverse-phase HPLC was used to purify to homogeneity a glycoprotein doublet of 15-16 kDa from culture supernatant. Biochemical analysis showed the purified recombinant I-309 glycoprotein to be indistinguishable from the natural I-309 glycoprotein constitutively secreted by the T-cell line IDP2. Purified recombinant I-309 stimulated migration of human monocytes but not neutrophils when tested by in vitro chemotaxis assay. Furthermore, the purified protein transiently increased cytoplasmic free calcium concentration in human peripheral blood monocytes but did not do so in lymphocytes or neutrophils. These results demonstrate that the I-309 gene encodes an inflammatory mediator that specifically stimulates human monocytes. Images

Miller, M D; Krangel, M S

1992-01-01

234

Studies of T-Lymphocytes in Preleukemic Disorders and Acute Nonlymphocytic Leukemia: In Vitro Radiosensitivity, Mitogenic Responsiveness, Colony Formation, and Enumeration of Lymphocytic Subpopulations  

Microsoft Academic Search

Tritiated thymidine incorporation in a whole blood Iympho- cyte stimulation test (LST) and lymphocyte colony forma- tion (CFU-L) from whole blood were measured following in vitro x-irradiation. Lymphocytes from patients with myelo- dysplastic disorders, acute nonlymphocytic leukemia. and patients at increased risk for leukemia because of their primary disease and\\/or cytotoxic therapy were found to be significantly more sensitive to

S. J. Knox; B. R. Greenberg; R. W. Anderson; L. S. Rosenblatt

1982-01-01

235

Inhibitory effect of esculentoside A on tumour necrosis factor ? production by human monocytes  

PubMed Central

Esculentoside A (EsA) is a saponin isolated from the roots of Phytolacca esculenta. Previous experiments have shown that it has strong anti-inflammatory effects. Tumour necrosis factor (TNF) is a very important inflammatory mediator. It is known that there are two types of TNF—TNF? is from macrophages/monocytes and TNF? is from activated lymphocytes. In order to study the mechanism of the anti-inflammatory effect of EsA, it was determined whether TNF? production from human peripheral monocytes was altered by EsA under lipopolysaccharide (LPS)-stimulated conditions. EsA was found to decrease TNF? production in a dose-dependent manner at concentrations higher than 1 ?mol/l EsA. Recent studies have shown that EsA has a curative effect on chocolate cyst and other inflammatory diseases. Our previous studies have shown that EsA could reduce the release of platelet activating factor (PAF) from rat macrophages, and inhibit interleukin-1 and interleukin-6 production from routine macrophages. The reducing effects of EsA on the release of TNF?, IL-1, IL-6 and PAF may explain its anti-inflammatory effect.

Fang, J.; Zheng, Q-Y.

1996-01-01

236

The effect of hyperglycemia and hypoglycemia on glucose transport and expression of glucose transporters in human lymphocytes B and T: an in vitro study.  

PubMed

Glucose transport in lymphocytes is regulated by many agents. It is interesting if only changing glucose concentrations in environment involves the impact on glucose uptake. The aims of this study were to investigate the impact of changing glucose concentrations in medium on deoxy-d-glucose uptake and what these conditions impact on the percent of cells with expression of chosen glucose transporters in human lymphocytes B and T. Isolated lymphocytes B and T obtained from healthy subject were cultivated in different concentrations of glucose. The experiments were carried out using tritium labeled deoxy-d-glucose and flow cytometry. In comparison to normoglycemia, hyperglycemia impairs the uptake of deoxy-d-glucose more than hypoglycemia. Lymphocytes B manifest significantly lower uptake of deoxy-d-glucose than lymphocytes T. Lymphocytes incubated in hyperglycemic and hypoglycemic medium show lower percent cells with expression of GLUT 1 and GLUT 3, and higher percent cells with expression of GLUT 4. The incubation of lymphocytes in hyperglycemic and hypoglycemic medium does not stimulate translocation of glucose transporters 3 and 4 to plasma membrane. Study shows that a change in concentration of glucose in incubation environment influence intracellular expression of glucose transporters in a significant part of lymphocytes B and T. PMID:22257417

Oleszczak, Bo?enna; Szablewski, Leszek; Pliszka, Monika

2012-05-01

237

Langerhans Cell Sarcoma Arising from Chronic Lymphocytic Lymphoma/Small Lymphocytic Leukemia: Lineage Analysis and BRAF V600E Mutation Study  

PubMed Central

Background: the phenomenon that histiocytic/dendritic cell sarcomas may be transformed from lymphoproliferative diseases is dubbed ‘transdifferentiation’. Langerhans cell sarcoma (LCS) transdifferentiated from chronic lymphocytic leukemia/small cell lymphoma (CLL/SLL) is extremely rare. The underlying mechanisms of LCS tumorogenesis and its transdifferentiation from CLL/SLL are largely unknown. Aims: the authors strive to further characterize LCS, to understand the potential molecular changes in LCS and the underlying mechanisms of CLL/SLL transformation to LCS. Materials and Methods: a progressively enlarging right inguinal lymph node from a 68-year-old female patient with a history of CLL was biopsied and submitted for flow cytometry analysis, routine hematoxylin, and eosin (H and E) stain and immunohistochemical study. Furthermore, clonality study (fluorescent in situ hybridization (FISH) analysis with a CLL panel probes) and BRAF V600E mutation study (pyrosequencing and immunostain) were performed. Results: two different neoplasms, LCS and CLL/SLL, were discovered to occur simultaneously in the same lymph node. These two entities were shown to be clonally related. More importantly, for the first time, BRAF V600E mutation was detected in LCS. Conclusions: LCS can be transdifferentiated from CLL/SLL and BRAF V600E mutation may provide the foundation for alternative therapy of LCS.

Chen, Weiwei; Jaffe, Ronald; Zhang, Linsheng; Hill, Charlie; Block, Anne Marie; Sait, Sheila; Song, Boer; Liu, Yunguang; Cai, Donghong

2013-01-01

238

Survival from acute non-lymphocytic leukaemia, 1971-88: a population based study.  

PubMed Central

Survival rates were studied among 1258 children with acute non-lymphocytic leukaemia diagnosed in 1971-88 and included in the population based National Registry of Childhood Tumours. Of the total, 147 (12%) died without receiving treatment. Among the remaining treated children, actuarial five year survival rates were 6% in 1971-4, 15% in 1975-9, 23% in 1980-3, and 40% in 1984-8. Infants aged less than 1 year had a significantly worse prognosis and there was a significant trend towards lower survival rates with increasing white cell count. No independent significant effects on survival were found with sex, French-American-British (FAB) subtype, or the presence or absence of Down's syndrome. Children entered in national trials had a higher survival rate than those who were not entered, and children treated at teaching hospitals had a higher survival rate than those who were treated elsewhere. Among the 535 (43%) children who survived at least one year from diagnosis no factor studied had a significant effect on survival, emphasising the importance of achieving first remission as a determinant of long term survival.

Stiller, C A; Eatock, E M

1994-01-01

239

Independent regulation of tumor necrosis factor and lymphotoxin production by human peripheral blood lymphocytes  

PubMed Central

We present evidence that human peripheral blood lymphocytes, free of contaminating monocytes, rapidly produce high levels of tumor necrosis factor (TNF) when stimulated with phorbol diester and calcium ionophore, and lower but significant levels of TNF when stimulated with mitogens. These two types of inducers act preferentially on T cells, both CD4+ and CD8+. NK cells produce TNF only when stimulated with phorbol diester and calcium ionophore, and they do so at a much lower level than T cells. The procedures used in the purification of lymphocytes and the differential ability to respond to various inducers allow us to exclude that monocytes or basophils contaminating the lymphocyte preparation participate in the production of TNF. In particular, LPS, a potent inducer of TNF production from monocytes, is unable to induce significant levels of TNF in the lymphocyte preparations. The TNF produced by lymphocytes has antigenic, physicochemical, and biochemical characteristics identical to those of the TNF produced by myeloid cell lines or monocytes upon stimulation with LPS. LT is also produced by lymphocyte preparations. Production of TNF and LT proteins in response to the different inducers is paralleled by accumulation of cytoplasmic TNF and LT mRNA. Both at mRNA and at protein levels, stimulation of T lymphocytes with phorbol diester and calcium ionophore preferentially induces TNF, whereas mitogen stimulation preferentially induces LT. Our data suggest that the TNF and LT genes, two closely linked genes encoding two partially homologous proteins with almost identical biological functions, are independently regulated in lymphocytes.

1987-01-01

240

Wolbachia heat shock protein 60 induces pro-inflammatory cytokines and apoptosis in monocytes in vitro  

PubMed Central

Recombinant Wolbachia heat shock protein 60 (rWmhsp60) induces gene expression of pro-inflammatory cytokines IL-1?, IL-6 and TNF-? in human monocytic cell line THP-1. In addition, it inhibits the phagocytic activity and does not alter the nitric oxide production by differentiated THP-1 macrophages, which corroborates with no significant change in inducible nitric oxide synthase gene expression in rWmhsp60 treated THP-1 monocytes. Further, 24 h stimulation of peripheral blood mononuclear cells from normal individuals by rWmhsp60 reveals that monocytes enter the late apoptotic stage, while lymphocytes do not show apoptosis. Thus these findings suggest that rWmhsp60 may contribute to inflammation mediated monocyte dysfunction in filarial pathogenesis.

Kamalakannan, Vijayan; Kirthika, Sreenivas; Haripriya, Kalyanaraman; Babu, Subash; Narayanan, Rangarajan Badri

2012-01-01

241

Platelets and Smooth Muscle Cells Affecting the Differentiation of Monocytes  

PubMed Central

Background Atherosclerosis is characterised by the formation of plaques. Monocytes play a pivotal role in plaque development as they differentiate into foam cells, a component of the lipid core whilst smooth muscle cells (SMC) are the principal cell identified in the cap. Recently, the ability of monocytes to differentiate into a myriad of other cell types has been reported. In lieu of these findings the ability of monocytes to differentiate into SMCs/smooth muscle (SM)-like cells was investigated. Method and Results Human monocytes were co-cultured with platelets or human coronary aortic SMCs and then analysed to assess their differentiation into SMCs/SM-like cells. The differentiated cells expressed a number of SMC markers and genes as determined by immunofluorescence staining and quantitative polymerase chain reaction (qPCR). CD array analysis identified marker expression profiles that discriminated them from monocytes, macrophages and foam cells as well as the expression of markers which overlapped with fibroblast and mesenchymal cells. Electron microscopy studies identified microfilaments and increased amounts of rough endoplasmic reticulum indicative of the SM- like cells, fibroblasts. Conclusions In the appropriate environmental conditions, monocytes can differentiate into SM-like cells potentially contributing to cap formation and plaque stability. Thus, monocytes may play a dual role in the development of plaque formation and ultimately atherosclerosis.

Williams, Michelle W. Y.; Guiffre, Ann K.; Fletcher, John P.

2014-01-01

242

Eosinophil Count and Neutrophil-Lymphocyte Count Ratio as Prognostic Markers in Patients with Bacteremia: A Retrospective Cohort Study  

Microsoft Academic Search

IntroductionThere is scarce evidence on the use of eosinophil count as a marker of outcome in patients with infection. The aim of this study was to evaluate whether changes in eosinophil count, as well as the neutrophil-lymphocyte count ratio (NLCR), could be used as clinical markers of outcome in patients with bacteremia.MethodsWe performed a retrospective study of patients with a

Roser Terradas; Santiago Grau; Jordi Blanch; Marta Riu; Pere Saballs; Xavier Castells; Juan Pablo Horcajada; Hernando Knobel

2012-01-01

243

The invention of lymphocytes  

PubMed Central

Summary Lamprey and hagfish are surviving representatives of the most ancient vertebrates. They possess adaptive immune systems based on a vast, somatically diversified repertoire of lymphocyte-bound antigen receptors. Despite these similarities to antibody and T cell receptors (TCR) of later vertebrates, the variable lymphocyte receptors (VLR) are not related to the immunoglobulin (Ig)-superfamily of genes; and instead of V(D)J recombination VLR are somatically assembled by a gene conversion process. However, recent studies have revealed two lamprey lymphocyte subsets so closely resembling B cells and T cells that separate lymphocyte lineages must have already existed in the ancestral vertebrate, before Ig/TCR emergence. VLR and Ig/TCR arose independently, but the convergent evolution they display actually reflects their selection in cells with specialized functions.

Hsu, Ellen

2011-01-01

244

Lymphocyte receptors for pertussis toxin  

SciTech Connect

We have investigated human T-lymphocyte receptors for pertussis toxin by affinity isolation and photoaffinity labeling procedures. T lymphocytes were obtained from peripheral human blood, surface iodinated, and solubilized in Triton X-100. The iodinated mixture was then passed through pertussis toxin-agarose, and the fractions were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Autoradiography of the fixed, dried gels revealed several bands in the pertussis toxin-bound fraction that were not observed in fractions obtained from histone or fetuin-agarose. Further investigations employed a photoaffinity labeling reagent, sulfosuccinimidyl 2-(p-azido-salicylamido)-1,3'-dithiopropionate, to identify pertussis toxin receptors in freshly isolated peripheral blood monocytic cells, T lymphocytes, and Jurkat cells. In all three cell systems, the pertussis toxin affinity probe specifically labeled a single protein species with an apparent molecular weight of 70,000 that was not observed when the procedure was performed in the presence of excess unmodified pertussis toxin. A protein comparable in molecular weight to the one detected by the photoaffinity labeling technique was also observed among the species that bound to pertussis toxin-agarose. The results suggest that pertussis toxin may bind to a 70,000-Da receptor in human T lymphocytes.

Clark, C.G.; Armstrong, G.D. (Univ. of Alberta, Edmonton (Canada))

1990-12-01

245

Reverse genetic studies of homologous DNA recombination using the chicken B-lymphocyte line, DT40.  

PubMed Central

DT40 is an avian leucosis virus-transformed chicken B-lymphocyte line which exhibits high ratios of targeted to random integration of transfected DNA constructs. This efficient targeted integration may be related to the ongoing diversification of the variable segment of the immunoglobulin gene through homologous DNA recombination-controlled gene conversion. DT40s are a convenient model system for making gene-targeted mutants. Another advantage is the relative tractability of these cells, which makes it possible to disrupt multiple genes in a single cell and to generate conditionally gene-targeted mutants including temperature-sensitive mutants. There are strong phenotypic similarities between murine and DT40 mutants of various genes involved in DNA recombination. These similarities confirm that the DT40 cell line is a reasonable model for the analysis of vertebrate DNA recombination, despite obvious concerns associated with the use of a transformed cell line, which may have certain cell-line-specific characteristics. Here we describe our studies of homologous DNA recombination in vertebrate somatic cells using reverse genetics in DT40 cells.

Sonoda, E; Morrison, C; Yamashita, Y M; Takata, M; Takeda, S

2001-01-01

246

Neutrophil-to-lymphocyte ratio in chronic obstructive pulmonary disease: a retrospective study.  

PubMed

Chronic obstructive pulmonary disease (COPD) is a common chronic inflammatory disease of the lung with a high mortality and morbidity rate. Some of the inflammatory markers such as C-reactive protein (CRP), leukocyte count are associated with COPD. In this study, we aimed to evaluate the role of neutrophil-to-lymphocyte ratio (NLR) in COPD patients comparing with the other well-known inflammatory markers. We retrospectively enrolled the laboratory results of 269 COPD patients of which 178 patients at stable period and 91 patients during acute exacerbation and 50 sex- and age- matched healthy controls. We found that NLR values of the stable COPD patients were significantly higher than those of the controls (P?

Günay, Ersin; Sar?nç Ula?l?, Sevinç; Akar, Olcay; Ahsen, Ahmet; Günay, Sibel; Koyuncu, Tülay; Unlü, Mehmet

2014-04-01

247

A genome-wide association study identifies multiple susceptibility loci for chronic lymphocytic leukemia.  

PubMed

Genome-wide association studies (GWAS) of chronic lymphocytic leukemia (CLL) have shown that common genetic variation contributes to the heritable risk of CLL. To identify additional CLL susceptibility loci, we conducted a GWAS and performed a meta-analysis with a published GWAS totaling 1,739 individuals with CLL (cases) and 5,199 controls with validation in an additional 1,144 cases and 3,151 controls. A combined analysis identified new susceptibility loci mapping to 3q26.2 (rs10936599, P = 1.74 × 10(-9)), 4q26 (rs6858698, P = 3.07 × 10(-9)), 6q25.2 (IPCEF1, rs2236256, P = 1.50 × 10(-10)) and 7q31.33 (POT1, rs17246404, P = 3.40 × 10(-8)). Additionally, we identified a promising association at 5p15.33 (CLPTM1L, rs31490, P = 1.72 × 10(-7)) and validated recently reported putative associations at 5p15.33 (TERT, rs10069690, P = 1.12 × 10(-10)) and 8q22.3 (rs2511714, P = 2.90 × 10(-9)). These findings provide further insights into the genetic and biological basis of inherited genetic susceptibility to CLL. PMID:24292274

Speedy, Helen E; Di Bernardo, Maria Chiara; Sava, Georgina P; Dyer, Martin J S; Holroyd, Amy; Wang, Yufei; Sunter, Nicola J; Mansouri, Larry; Juliusson, Gunnar; Smedby, Karin E; Roos, Göran; Jayne, Sandrine; Majid, Aneela; Dearden, Claire; Hall, Andrew G; Mainou-Fowler, Tryfonia; Jackson, Graham H; Summerfield, Geoffrey; Harris, Robert J; Pettitt, Andrew R; Allsup, David J; Bailey, James R; Pratt, Guy; Pepper, Chris; Fegan, Chris; Rosenquist, Richard; Catovsky, Daniel; Allan, James M; Houlston, Richard S

2014-01-01

248

Search for Cellular Stress Biomarkers in Lymphocytes from Patients with Multiple Sclerosis: A Pilot Study  

PubMed Central

Multiple Sclerosis (MS) is a chronic disease of the central nervous system, the etiology of which, although not completely known, involves inflammation and autoimmunity. In the present study we aimed at identifying molecular markers of apoptosis, cellular stress and DNA damage in isolated peripheral blood mononuclear cells (PBMCs) of MS patients. The analysis was carried on 19 relapsing-remitting untreated MS patients and 13 healthy individuals. We investigated the emergency-driven synthesis of poly(ADP-ribose) (PAR), the expression level of the constitutive enzyme poly(ADP-ribose) polymerase-1 (PARP-1) and the DNA damage-induced phosphorylation of histone H2AX. PAR accumulation, PARP-1 and phosphorylated H2AX (?H2AX) were detected by immunofluorescence experiments on PBMCs isolated from 19 patients and 13 healthy volunteers. Our results show for the first time a net increased amount in PAR and ?H2AX in MS patients compared to healthy individuals. Patients were further subdivided in three groups, according to the neuroimaging (MRI)-based classification of disease phase. Remarkably, we found a positive correlation between the level of ?H2AX and MS aggressiveness. In addition, apoptosis in PBMCs was monitored by flow cytometry of both phosphatidylserine exposure (revealed by Annexin V-FITC labeling) and membrane permeability to propidium iodide. Our observations provide the evidence that the number of apoptotic cells was significantly higher in patients compared to healthy individuals, thus suggesting that apoptosis could affect MS lymphocyte function.

Grecchi, Sabrina; Mazzini, Giuliano; Lisa, Antonella; Armentero, Marie-Therese; Bergamaschi, Roberto; Romani, Alfredo; Blandini, Fabio; Di Perri, Carol; Scovassi, Anna Ivana

2012-01-01

249

Search for cellular stress biomarkers in lymphocytes from patients with multiple sclerosis: a pilot study.  

PubMed

Multiple Sclerosis (MS) is a chronic disease of the central nervous system, the etiology of which, although not completely known, involves inflammation and autoimmunity. In the present study we aimed at identifying molecular markers of apoptosis, cellular stress and DNA damage in isolated peripheral blood mononuclear cells (PBMCs) of MS patients. The analysis was carried on 19 relapsing-remitting untreated MS patients and 13 healthy individuals. We investigated the emergency-driven synthesis of poly(ADP-ribose) (PAR), the expression level of the constitutive enzyme poly(ADP-ribose) polymerase-1 (PARP-1) and the DNA damage-induced phosphorylation of histone H2AX. PAR accumulation, PARP-1 and phosphorylated H2AX (?H2AX) were detected by immunofluorescence experiments on PBMCs isolated from 19 patients and 13 healthy volunteers. Our results show for the first time a net increased amount in PAR and ?H2AX in MS patients compared to healthy individuals. Patients were further subdivided in three groups, according to the neuroimaging (MRI)-based classification of disease phase. Remarkably, we found a positive correlation between the level of ?H2AX and MS aggressiveness. In addition, apoptosis in PBMCs was monitored by flow cytometry of both phosphatidylserine exposure (revealed by Annexin V-FITC labeling) and membrane permeability to propidium iodide. Our observations provide the evidence that the number of apoptotic cells was significantly higher in patients compared to healthy individuals, thus suggesting that apoptosis could affect MS lymphocyte function. PMID:23028690

Grecchi, Sabrina; Mazzini, Giuliano; Lisa, Antonella; Armentero, Marie-Therese; Bergamaschi, Roberto; Romani, Alfredo; Blandini, Fabio; Di Perri, Carol; Scovassi, Anna Ivana

2012-01-01

250

Cellular Activation and Intracellular HCV Load in Peripheral Blood Monocytes Isolated from HCV Monoinfected and HIV-HCV Coinfected Patients  

PubMed Central

Background During HCV infection, the activation status of peripheral blood monocytes and its impact on HCV replication are poorly understood. We hypothesized that a modified activation of peripheral blood monocytes in HIV-HCV coinfected compared to HCV monoinfected patients may contribute to different monocytes reservoirs of HCV replication. Methods We performed a case-control analysis involving HCV-infected patients with and without HIV coinfection. In peripheral blood mononuclear cells (PBMCs), peripheral blood lymphocytes (PBLs) and peripheral blood monocytes isolated from HCV monoinfected and HIV-HCV coinfected patients, intracellular HCV load and a marker of cellular activation, nuclear factor-kappaB (NF-?B) activation, were quantified using intracellular detection of HCV-core protein and electrophoretic mobility shift assay, respectively. Results Intracellular HCV loads were higher in monocytes isolated from HIV-HCV coinfected patients than in those of monoinfected patients. Among PBMCs isolated from HIV-HCV coinfected patients, intracellular HCV loads were higher in monocytes compared to PBLs. Cellular activation as measured by NF-?B activation was higher in monocytes isolated from HIV-HCV coinfected patients than in those of monoinfected patients. Conclusions Our results reveal the peripheral blood monocytes as an important extrahepatic reservoir for HCV in HIV-HCV coinfected patients and indicate a potential association between the activation state of monocytes and the size of the HCV reservoir in HIV-HCV coinfected patients.

Dichamp, Isabelle; Di Martino, Vincent; Herbein, Georges

2014-01-01

251

Photochemotherapy induces the apoptosis of monocytes without impairing their function  

PubMed Central

Background Extracorporeal photopheresis (ECP) is a powerful therapy currently used to treat various haematological disorders as in graft versus host disease (GVHD). Clinical data clearly demonstrate its efficacy and immunomodulation towards the pathogenic T cells. However, ECP mechanism of action is still poorly understood. Monocytes represent up to 30% of the total amount of treated cells and are known to play an important role in adaptive immunity. However, data from previous reports analyzing the effect of PUVA (psoralen and UV-A irradiation) on their functions are heterogeneous. In this study, we focused on the effect of PUVA on human monocytes functions in adaptive immunity. Design and Methods Purified human monocytes were treated in vitro by PUVA. We measured their kinetic of apoptosis following the treatment. We also determine if their phenotype and functionalities were modified. Finally we assessed the functionalities of PUVA-treated monocytes-derived dendritic cells (DC). Results PUVA treatment sentenced purified monocytes to die in six days and immediately altered their migratory capacities without impairing their ability of endocytosis. It also up-regulated co-stimulatory molecules and production of inflammatory cytokines upon activation and consequently stimulated allogeneic or autologous T cells as efficiently as untreated monocytes. Moreover, PUVA-treated monocytes retained their ability to differentiate into fully functional DC that maturated and stimulated T cells as well as normal DC. Conclusions Our data demonstrate that monocytes undergo apoptosis and loose a part of their migratory capacity following ECP and the surviving cell functionalities are not impaired, suggesting that monocytes have a minor effect on ECP-mediated immunomodulation.

Hannani, Dalil; Gabert, Francoise; Laurin, David; Sall, Mariam; Molens, Jean-Paul; Hequet, Olivier; Chaperot, Laurence; Plumas, Joel

2010-01-01

252

Immunological characterization and transcription profiling of peripheral blood (PB) monocytes in children with autism spectrum disorders (ASD) and specific polysaccharide antibody deficiency (SPAD): case study  

PubMed Central

Introduction There exists a small subset of children with autism spectrum disorders (ASD) characterized by fluctuating behavioral symptoms and cognitive skills following immune insults. Some of these children also exhibit specific polysaccharide antibody deficiency (SPAD), resulting in frequent infection caused by encapsulated organisms, and they often require supplemental intravenous immunoglobulin (IVIG) (ASD/SPAD). This study assessed whether these ASD/SPAD children have distinct immunological findings in comparison with ASD/non-SPAD or non-ASD/SPAD children. Case description We describe 8 ASD/SPAD children with worsening behavioral symptoms/cognitive skills that are triggered by immune insults. These ASD/SPAD children exhibited delayed type food allergy (5/8), treatment-resistant seizure disorders (4/8), and chronic gastrointestinal (GI) symptoms (5/8) at high frequencies. Control subjects included ASD children without SPAD (N = 39), normal controls (N = 37), and non-ASD children with SPAD (N = 12). Discussion and Evaluation We assessed their innate and adaptive immune responses, by measuring the production of pro-inflammatory and counter-regulatory cytokines by peripheral blood mononuclear cells (PBMCs) in responses to agonists of toll like receptors (TLR), stimuli of innate immunity, and T cell stimulants. Transcription profiling of PB monocytes was also assessed. ASD/SPAD PBMCs produced less proinflammatory cytokines with agonists of TLR7/8 (IL-6, IL-23), TLR2/6 (IL-6), TLR4 (IL-12p40), and without stimuli (IL-1ß, IL-6, and TNF-?) than normal controls. In addition, cytokine production of ASD/SPAD PBMCs in response to T cell mitogens (IFN-?, IL-17, and IL-12p40) and candida antigen (Ag) (IL-10, IL-12p40) were less than normal controls. ASD/non-SPAD PBMDs revealed similar results as normal controls, while non-ASD/SPAD PBMCs revealed lower production of IL-6, IL-10 and IL-23 with a TLR4 agonist. Only common features observed between ASD/SPAD and non-ASD/SPAD children is lower IL-10 production in the absence of stimuli. Transcription profiling of PB monocytes revealed over a 2-fold up (830 and 1250) and down (653 and 1235) regulation of genes in ASD/SPAD children, as compared to normal (N = 26) and ASD/non-SPAD (N = 29) controls, respectively. Enriched gene expression of TGFBR (p < 0.005), Notch (p < 0.01), and EGFR1 (p < 0.02) pathways was found in the ASD/SPAD monocytes as compared to ASD/non-SPAD controls. Conclusions The Immunological findings in the ASD/SPAD children who exhibit fluctuating behavioral symptoms and cognitive skills cannot be solely attributed to SPAD. Instead, these findings may be more specific for ASD/SPAD children with the above-described clinical characteristics, indicating a possible role of these immune abnormalities in their neuropsychiatric symptoms.

2012-01-01

253

Comparative analysis of canine monocyte- and bone-marrow-derived dendritic cells  

PubMed Central

Dendritic cells (DC) represent a heterogeneous cell family of major importance for innate immune responses against pathogens and antigen presentation during infection, cancer, allergy and autoimmunity. The aim of the present study was to characterize canine DC generated in vitro with respect to their phenotype, responsiveness to toll-like receptor (TLR) ligands and T-cell stimulatory capacity. DC were derived from monocytes (MoDC) and from bone marrow hematopoietic cells cultured with either Flt3-ligand (FL-BMDC) or with GM-CSF (GM-BMDC). All three methods generated cells with typical DC morphology that expressed CD1c, CD11c and CD14, similar to macrophages. However, CD40 was only found on DC, CD206 on M? and BMDC, but not on monocytes and MoDC. CD1c was not found on monocytes but on all in vitro differentiated cells. FL-BMDC and GM-BMDC were partially positive for CD4 and CD8. CD45RA was expressed on a subset of FL-BMDC but not on MoDC and GM-BMDC. MoDC and FL-DC responded well to TLR ligands including poly-IC (TLR2), Pam3Cys (TLR3), LPS (TLR4) and imiquimod (TLR7) by up-regulating MHC II and CD86. The generated DC and M? showed a stimulatory capacity for lymphocytes, which increased upon maturation with LPS. Taken together, our results are the basis for further characterization of canine DC subsets with respect to their role in inflammation and immune responses.

Ricklin Gutzwiller, Meret Elisabeth; Moulin, Herve Raphael; Zurbriggen, Andreas; Roosje, Petra; Summerfield, Artur

2010-01-01

254

Changes in T-lymphocyte distribution associated with ingestion of aldicarb-contaminated drinking water: a follow-up study.  

PubMed

The carbamate pesticide, aldicarb, is the most commonly found man-made groundwater contaminant in Wisconsin. A 1985 study linked ingestion of aldicarb-contaminated drinking water with altered T-cell distributions, specifically an increase in the mean number of CD8+ (T8) T cells. To further evaluate this finding, a follow-up study was done in 1987. Of the 50 Portage County, Wisconsin, women who participated in the first study, 45 participated in the follow-up: 18 formerly exposed and 27 formerly unexposed. In our follow-up study, only 5 women were found to be currently exposed to aldicarb. This group of 5 women, compared to 39 unexposed women who had peripheral blood specimens taken, had an increased percentage of lymphocytes and an increased number of CD2+ T cells, due to an increased number of total CD8+ T cells. Although the number of exposed persons was small, the increases in percentage lymphocytes and absolute numbers of CD2+ and CD8+ T cells were consistent with a dose-response relationship. No identified drinking water contaminant other than aldicarb could explain these findings. These results support earlier evidence linking aldicarb exposure and lymphocyte distribution changes. Although adverse clinical effects have not been documented, the widespread use of this chemical and consequent potential for widespread exposure indicate a clear need for further research on this issue. PMID:2137083

Mirkin, I R; Anderson, H A; Hanrahan, L; Hong, R; Golubjatnikov, R; Belluck, D

1990-02-01

255

Ovine lentivirus is macrophagetropic and does not replicate productively in T lymphocytes.  

PubMed Central

The lentiviruses of sheep, goats, and horses cause chronic multiorgan disease in which macrophages are highly permissive for viral replication. Monocytes, which mature into macrophages, are thought to be latently infected with lentivirus, but the extent to which other leukocytes are infected is unknown. Dendritic cells have not been studied separately from monocytes and T-cell subsets have not been examined in previous attempts to identify infected cells in peripheral blood mononuclear cells (PBMC). We found no evidence of T-cell tropism using an animal-passaged, pathogenic ovine lentivirus. Phytohemagglutinin-stimulated infectious PBMC produced 20-fold less virus than differentiated macrophages, and cocultivation of infectious PBMC with fresh, uninfected phytohemagglutinin blasts did not facilitate virus replication. Furthermore, central lymph cells, the best in vivo source of purified lymphocytes, lacked virus and did not yield virus upon in vitro cultivation. In contrast, cultivated blood-derived macrophages were highly permissive for viral replication. To identify the latently infected PBMC, PBMC from infected sheep were selectively depleted of monocytes and B cells by passage over nylon wool and then of nonadherent cells bearing CD4, CD8, T19, gamma delta T-cell receptor, CD45RA, or major histocompatibility complex class II antigens by panning. Removal of adherent monocytes and B cells or of adherent cells and the three major T-cell subsets (CD4+, CD8+, T19+) did not decrease the infectivity of PBMC. The richest sources of infected cells in fresh PBMC were CD45RA+ and major histocompatibility complex class II+ nonadherent cells, which are three characteristics of dendritic cells. Thus, the dendritic cell, and not the monocyte or the CD4+ cell, is probably the predominant infected cell type in blood. Images

Gorrell, M D; Brandon, M R; Sheffer, D; Adams, R J; Narayan, O

1992-01-01

256

Factors predicting response and graft-versus-host disease after donor lymphocyte infusions: a study on 593 infusions  

Microsoft Academic Search

In the present study, we analyze factors predicting graft-versus-host disease (GvHD) and response after donor lymphocyte infusions (DLI). A total of 100 patients received 593 DLI between June 1990 and December 2000 in a bulk dose (n=14) or in escalating dose infusions (n=86). Patients were analyzed after stratification for type of relapse: (1) molecular relapse (n=6), (2) cytogenetic relapse (n=20),

A M Raiola; M T Van Lint; M Valbonesi; T Lamparelli; F Gualandi; D Occhini; S Bregante; C di Grazia; A Dominietto; M Soracco; C Romagnani; F Vassallo; M Casini; B Bruno; F Frassoni; A Bacigalupo

2003-01-01

257

Monocytes stimulated by 110-kDa fibronectin fragments suppress proliferation of anti-CD3-activated T cells.  

PubMed

One hundred ten to 120-kDa fragments of fibronectin (FNf), generated by proteases released in the course of tissue injury and inflammation, stimulate monocytes to produce proinflammatory cytokines, promote mononuclear leukocytes (MNL) transendothelial migration, up-regulate monocyte CD11b and CD86 expression, and induce monocyte-derived dendritic cell differentiation. To investigate whether the proinflammatory consequences of FNf are offset by responses that can suppress proliferation of activated T lymphocytes, we investigated the effect of FNf-treated MNL on autologous T lymphocytes induced to proliferate by substrate-immobilized anti-CD3. FNf-stimulated MNL suppressed anti-CD3-induced T cell proliferation through both contact-dependent and contact-independent mechanisms. Contact-independent suppression was mediated, at least in part, by IL-10 and TGF-beta released by the FNf-stimulated MNL. After 24-48 h exposure to FNf, activated T cells and monocytes formed clusters displaying CD25, CD14, CD3, and CD4 that were not dissociable by chelation of divalent cations. Killing monocytes with l-leucine methyl ester abolished these T cell-monocyte clusters and the ability of the FNf-stimulated MNL to suppress anti-CD3 induced T cell proliferation. Thus, in addition to activating MNL and causing them to migrate to sites of injury, FNf appears to induce suppressor monocytes. PMID:16116227

Birdsall, Holly H; Porter, Wendy J; Trial, JoAnn; Rossen, Roger D

2005-09-01

258

Monocytes in sterile inflammation: recruitment and functional consequences.  

PubMed

Monocytes play an important role in initiating innate immune responses. Three subsets of these cells have been defined in mice including classical, nonclassical and intermediate monocytes. Each of these cell types has been extensively studied for their role in infectious diseases. However, their role in sterile injury as occurs during ischemia-reperfusion injury, atherosclerosis, and trauma has only recently been the focus of investigations. Here, we review mechanisms of monocyte recruitment to sites of sterile injury, their modes of action, and their effect on disease outcome in murine models with some references to human studies. Therapeutic strategies to target these cells must be developed with caution since each monocyte subset is capable of mediating either anti- or pro-inflammatory effects depending on the setting. PMID:24310705

Spahn, Jessica H; Kreisel, Daniel

2014-06-01

259

Expression of monocyte chemotactic protein-1 by monocytes and endothelial cells exposed to thrombin.  

PubMed Central

Thrombin, in addition to being a key enzyme in hemostasis, affects a series of endothelial and leukocyte functions and thus may be involved in the regulation of inflammatory reactions. Because leukocyte recruitment and activation are important events in inflammatory and thrombotic processes, in this study we have examined the possibility that thrombin induces the production of a cytokine chemotactic for mononuclear phagocytes. Human peripheral blood mononuclear cells (PBMC) exposed in vitro to thrombin expressed transcripts of monocyte chemotactic protein-1 (MCP-1; alternative acronyms: JE, monocyte chemotactic and activating factor, tumor-derived chemotactic factor). Thrombin was two- to threefold less effective than endotoxin in inducing MCP-1 transcripts in PBMC. Among circulating mononuclear cells, monocytes were identified as the cells expressing MCP-1 in response to thrombin. Monocytes expressed thrombin receptor transcripts. Boiling, hirudin, antithrombin III, and mutation of the catalytic site serine 205 into alanine) blocked the capacity of thrombin to induce MCP-1 expression. The thrombin receptor-activating peptide mimicked the effect of thrombin in inducing MCP-1 expression. Induction of MCP-1 transcript by thrombin was not reduced by blocking interleukin-1 and tumor necrosis factor, suggesting that these mediators are not involved in thrombin-induced expression of MCP-1. In addition to monocytes, endothelial cells (EC) also expressed MCP-1 in response to thrombin, although at lower levels compared with monocytes. Actinomycin D experiments indicated that induction of MCP-1 by thrombin in PBMC and EC was gene transcription dependent. The inhibition of protein synthesis blocked thrombin-induced MCP-1 expression in PBMC, whereas it superinduced both constitutive and thrombin-inducible expression of MCP-1 in EC, indicating different mechanisms of regulation of this gene in mononuclear phagocytes versus endothelial cells. Thrombin stimulated mononuclear cells and EC to release chemotactic activity for monocytes that could be inhibited by absorption with anti-MCP-1 antibodies. Induction of a chemotactic cytokine for monocytes by thrombin points to the importance of this enzyme in regulating inflammatory processes and further indicates that hemostasis, inflammation, and immunity are strictly interconnected processes. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 6 Figure 7 Figure 8

Colotta, F.; Sciacca, F. L.; Sironi, M.; Luini, W.; Rabiet, M. J.; Mantovani, A.

1994-01-01

260

Energy Metabolism of Monocytic Ehrlichia.  

National Technical Information Service (NTIS)

We investigated if the monocytic Ehrlichia are totally dependent on their host cells for energy, or, as Rickettsia, are capable of some ATP synthesis in vitro. The Miyayama strain Ehrlichia sennetsu and the Maryland and Illinois strains of Enrlichia risti...

E. Weiss G. A. Dasch J. C. Williams Y. H. Kang

1989-01-01

261

A pilot study on cytotoxic T lymphocyte-4 gene polymorphisms in urinary schistosomiasis.  

PubMed

Urinary schistosomiasis is caused by the digenetic trematode Schistosoma haematobium, characterized by accumulation of eggs in the genitourinary tract. Cytotoxic T-lymphocyte antigen 4 (CTLA-4) can play an important role in parasitic infection due to its major role as a negative regulator of T-cell activation and proliferation. This study was performed in patients with schistosomiasis and healthy controls to analyze the allele and genotype frequencies of four CTLA-4 gene polymorphisms. The CTLA-4 gene was amplified using Taqman real-time polymerase chain reaction, and allele and genotypes of 49 patients with schistosomiasis were analyzed using allelic discrimination analysis followed by subsequent direct sequencing. The results were compared with healthy control subjects. The frequencies of CTLA-4 rs733618 A allele at position -1722 (p=0.001), rs11571316 C allele at position -1577 (p<0.001), and rs231775 A allele at position +49 (p=0.002) in the patient group were significantly higher than the control group. The rs733618 AA genotype (p=0.001), rs11571316 CC genotype (p<0.001), and rs231775 AA genotype (p=0.007) were also significantly overrepresented. Meanwhile, rs733618 AG genotype (p=0.001), rs11571316 CT genotype (p=0.02), and rs231775 GG genotype (p=0.029) were significantly decreased in the patients with schistosomiasis, as compared with the controls. No significant difference was observed in both allele and genotype of rs16841252. The results of this study suggest that the rs733618, rs11571316, and rs231775 polymorphisms in the CTLA-4 gene may influence susceptibility to schistosomiasis infection in the Gabonese children. PMID:22288822

Idris, Zulkarnain Md; Yazdanbakhsh, Maria; Adegnika, Ayola Akim; Lell, Bertrand; Issifou, Saadou; Noordin, Rahmah

2012-06-01

262

A Pilot Study on Cytotoxic T Lymphocyte-4 Gene Polymorphisms in Urinary Schistosomiasis  

PubMed Central

Urinary schistosomiasis is caused by the digenetic trematode Schistosoma haematobium, characterized by accumulation of eggs in the genitourinary tract. Cytotoxic T-lymphocyte antigen 4 (CTLA-4) can play an important role in parasitic infection due to its major role as a negative regulator of T-cell activation and proliferation. This study was performed in patients with schistosomiasis and healthy controls to analyze the allele and genotype frequencies of four CTLA-4 gene polymorphisms. The CTLA-4 gene was amplified using Taqman real-time polymerase chain reaction, and allele and genotypes of 49 patients with schistosomiasis were analyzed using allelic discrimination analysis followed by subsequent direct sequencing. The results were compared with healthy control subjects. The frequencies of CTLA-4 rs733618 A allele at position ?1722 (p=0.001), rs11571316 C allele at position ?1577 (p<0.001), and rs231775 A allele at position +49 (p=0.002) in the patient group were significantly higher than the control group. The rs733618 AA genotype (p=0.001), rs11571316 CC genotype (p<0.001), and rs231775 AA genotype (p=0.007) were also significantly overrepresented. Meanwhile, rs733618 AG genotype (p=0.001), rs11571316 CT genotype (p=0.02), and rs231775 GG genotype (p=0.029) were significantly decreased in the patients with schistosomiasis, as compared with the controls. No significant difference was observed in both allele and genotype of rs16841252. The results of this study suggest that the rs733618, rs11571316, and rs231775 polymorphisms in the CTLA-4 gene may influence susceptibility to schistosomiasis infection in the Gabonese children.

Idris, Zulkarnain Md; Yazdanbakhsh, Maria; Adegnika, Ayola Akim; Lell, Bertrand; Issifou, Saadou

2012-01-01

263

Radiosensitivity of lymphocytes among Filipinos: final report.  

National Technical Information Service (NTIS)

This report is about the studies on the radiosensitivity of Filipino lymphocytes to radiation that can elucidate on the potential of blood chromosomes as biological dosimeters. The objective of this study is to determine the radiosensitivity of lymphocyte...

F. I. S. Medina J. S. Gregorio C. P. Aguilar E. E. Poblete

1996-01-01

264

Comparative studies by comet test and SCE analysis in human lymphocytes from 200 healthy subjects  

Microsoft Academic Search

The comet test (single cell gel electrophoresis, SCGE) appears to be a promising tool to estimate DNA damage at the single cell level and it provides information on the presence of damage among individual cells. Previously, we analyzed the degree of DNA damage in peripheral human lymphocytes from 100 healthy subjects living in Pisa (Italy) taking into account age, gender

Cecilia Betti; Tania Davini; Liliana Giannessi; Nicola Loprieno; Roberto Barale

1995-01-01

265

Chromosome study of 6-thioguanine-resistant mutants in T lymphocytes of Hiroshima atomic bomb survivors.  

National Technical Information Service (NTIS)

Cytogenetic characterizations were made of lymphocyte colonies established from somatic mutation assays for 6-thioguanine (TG) resistance in Hiroshima atomic bomb survivors. G-banded chromosomes were analyzed in both TG-resistant (TG(sup r)) and wild-type...

Y. Kodama, M. Hakoda, H. Shimba, A. A. Awa, M. Akiyama

1989-01-01

266

Syzygium cumini (Jamun) reduces the radiation-induced DNA damage in the cultured human peripheral blood lymphocytes: a preliminary study.  

PubMed

The effects of various concentrations (0.0, 1.56, 3.125, 6.25, 12.5, 25, 50 and 100 microg/ml) of the leaf extract of Syzygium cumini Linn. or Eugenia cumini (SC; black plum, Jamun, family Myrtaceae) was studied on the alteration in the radiation-induced micronuclei formation in the cultured human peripheral blood lymphocytes. Treatment of lymphocytes to various concentrations of SC resulted in a dose dependent increase in the micronuclei-induction, especially after 25-100 microg/ml extract. The exposure of human lymphocytes to various concentrations of SC extract before 3 Gy gamma-irradiation resulted in a significant decline in the micronuclei-induction at all the drug doses when compared with the non-drug treated irradiated cultures. A nadir in MNBNC frequency was observed for 12.5 microg/ml drug concentration, where the MNBNC frequency was approximately fourfold lower than that of the non-drug treated irradiated cultures. Therefore, this dose may be considered as an optimum dose for radiation protection. Our study demonstrates that the leaf extract of S. cumini, a plant traditionally used to treat diabetic disorders protects against the radiation-induced DNA damage. PMID:12084616

Jagetia, Ganesh Chandra; Baliga, Manjeshwar Shrinath

2002-06-01

267

Flow cytometric identification of CD93 expression on naive T lymphocytes (CD4(+)CD45RA (+) cells) in human neonatal umbilical cord blood.  

PubMed

Human CD93 has a molecular weight of about 100 kDa and is selectively expressed by myeloid cell lineages in peripheral blood (PB) mononuclear cells. Although CD93 was initially identified as a receptor for complement component 1, subcomponent q phagocytosis (C1qRp) involved in the C1q-mediated enhancement of the phagocytosis of various antigens, several recent studies have reported that CD93 is not a receptor for the C1q-mediated enhancement of phagocytosis. The expression patterns of CD93 have been previously investigated in PB mononuclear cells (lymphocytes, monocytes, and granulocytes) from adult PB and neonatal umbilical cord blood (UCB), and the expression of CD93 was not found on lymphocytes from either normal adult PB or neonatal UCB. However, the detection of CD93 expression in neonatal UCB using CD93 monoclonal antibodies (mAbs) that recognize different antigenic epitopes remains poorly understood. In this study, we examined the expression of CD93 on lymphocytes, monocytes, and granulocytes from neonatal UCB using four different types of CD93 mAb detection probes, mNI-11, R139, R3, and X-2, using flow cytometric and western blot analyses. We found that CD93, as defined using all four mAbs, was expressed on monocytes and granulocytes in PB mononuclear cells from adult PB and neonatal UCB. On the other hand, we observed for the first time that the expression of CD93 on lymphocytes in neonatal UCB can only be detected using the mNI-11 mAb, established in our laboratory, and not with commercially available CD93 mAbs (R139, R3, and X-2). However, CD93 expression on lymphocytes from normal adults was not detected using any of the four CD93 mAbs. Two-color flow cytometric analyses showed that the CD93 recognized by mNI-11 mAb was expressed on CD3(+) T lymphocytes (mainly CD4(+) helper T lymphocytes), but not on CD19(+) B lymphocytes or on CD8(+) suppressor/cytotoxic T lymphocytes from neonatal UCB. In addition, CD93 was expressed on CD45RA(+) (naive antigen) lymphocytes from neonatal UCB, but not on CD45RO(+) (memory antigen) lymphocytes from neonatal UCB or on CD45RA(+) and CD45RO(+) lymphocytes from normal adult PB. Three-color flow cytometric analysis showed that CD93 was co-expressed on naive T lymphocytes (CD4(+)CD45RA(+)) from neonatal UCB. In a western blot analysis, the CD93 mAb (mNI-11) immunoprecipitated at a molecular weight of 98 kDa, identified as a CD93 molecule, in the CD4(+)CD45RA(+) cells from neonatal UCB but not from adult PB, similar to the results in the human monocyte-like cell line U937 (human CD93-positive cells). Taken together, these results provide the first direct evidence of a novel/naive cell population (CD4(+)CD45RA(+)CD93(+)) in neonatal UCB that may have an important role in cell biology, transplantation, and immature/mature immune responses. PMID:20512406

Ikewaki, Nobunao; Yamao, Hiromichi; Kulski, Jerzy K; Inoko, Hidetoshi

2010-09-01

268

Differential expression of Ia molecules by human monocytes.  

PubMed Central

Human immune response genes can be divided into three distinct loci, each of which codes for three distinct families of Ia molecules: HLA-SB, HLA-DC, and HLA-DR. The tissue distribution and function of only one of these Ia molecules, HLA-DR, has been thoroughly studied. Using monoclonal antibodies, we examined the display of HLA-DR and HLA-DC molecules by adherent, human peripheral blood monocytes. The results of these studies demonstrate that although all human peripheral blood monocytes display easily detectable HLA-DR molecules, only 50% display easily detectable HLA-DC molecules. Separation of peripheral blood monocytes into HLA-DC+ and HLA-DC- cells demonstrates that each population displays an equivalent density of HLA-DR molecules. Therefore, on the basis of differences in their display of these two Ia molecules, adherent peripheral blood monocytes can be divided into two broad populations: HLA-DR+, HLA-DC+, and HLA-DR+, HLA-DC-. Despite the dis-coordinate display of these Ia antigens, the expression of both HLA-DR and HLA-DC can be regulated by a common signal, gamma interferon (IFN-gamma). Incubation of monocytes for 96 h in autologous serum leads to a marked decrease in the expression of both HLA-DR and HLA-DC. Addition of recombinant IFN-gamma to the cultures leads to reexpression of both HLA-DR and HLA-DC to levels comparable to those seen in fresh monocytes. In addition, although IFN-gamma does not modulate all monocyte surface markers, it can be demonstrated to modulate expression of one marker, MAC 120, in a manner similar to that observed for Ia antigens. These studies demonstrate that among human peripheral blood monocytes, the distribution of the Ia molecule, HLA-DC, is not coordinate with that of HLA-DR, although both respond to the same regulatory signal.

Gonwa, T A; Stobo, J D

1984-01-01

269

[Effects of radiotherapy on lymphocyte populations in lung cancer].  

PubMed

The authors report on the results of the immune monitoring of a study population of 31 patients with lung cancer who were treated with radiotherapy. A synthetic thymic pentapeptide, thymopentin, was employed whose effect was evaluated on the immunological parameters analyzed. After radiotherapy, a considerable and homogeneous decrement was observed in several lymphocytic subsets (less sensible in activated T-cells), together with a progressive decrement in the helper/suppressor ratio, in the long run. Monocytes and null cells showed more radioresistance. Thymopentin had no influence on the tested immunological parameters up to 6 months after radiotherapy; later on, a slightly more balanced helper/suppressor ratio could be noticed in the surviving patients who had been treated with thymopentin. PMID:3060904

Gava, A; Moro, L; De Angeli, S; Coghetto, F; Marazzato, G; Fantin, P; Patrese, P

1988-11-01

270

Genome-wide association study for T lymphocyte subpopulations in swine  

PubMed Central

Background Lymphocytes act as a major component of the adaptive immune system, taking very crucial responsibility for immunity. Differences in proportions of T-cell subpopulations in peripheral blood among individuals under same conditions provide evidence of genetic control on these traits, but little is known about the genetic mechanism of them, especially in swine. Identification of the genetic control on these variants may help the genetic improvement of immune capacity through selection. Results To identify genomic regions responsible for these immune traits in swine, a genome-wide association study was conducted. A total of 675 pigs of three breeds were involved in the study. At 21 days of age, all individuals were vaccinated with modified live classical swine fever vaccine. Blood samples were collected when the piglets were 20 and 35 days of age, respectively. Seven traits, including the proportions of CD4+, CD8+, CD4+CD8+, CD4+CD8?, CD4?CD8+, CD4?CD8? and the ratio of CD4+ to CD8+ T cells were measured at the two ages. All the samples were genotyped for 62,163 single nucleotide polymorphisms (SNP) using the Illumina porcineSNP60k BeadChip. 40833 SNPs were selected after quality control for association tests between SNPs and each immune trait considered based on a single-locus regression model. To tackle the issue of multiple testing in GWAS, 10,000 permutations were performed to determine the chromosome-wise and genome-wise significance levels of association tests. In total, 61 SNPs with chromosome-wise significance level and 3 SNPs with genome-wise significance level were identified. 27 significant SNPs were located within the immune-related QTL regions reported in previous studies. Furthermore, several significant SNPs fell into the regions harboring known immunity-related genes, 14 of them fell into the regions which harbor some known T cell-related genes. Conclusions Our study demonstrated that genome-wide association studies would be a feasible way for revealing the potential genetics variants affecting T-cell subpopulations. Results herein lay a preliminary foundation for further identifying the causal mutations underlying swine immune capacity in follow-up studies.

2012-01-01

271

Effect of IFN-gamma on the proliferation of Toxoplasma gondii in monocytes and monocyte-derived macrophages from AIDS patients.  

PubMed Central

This study was undertaken to determine whether the activity of monocytes and monocyte-derived macrophages (MDM) from acquired immune deficiency syndrome (AIDS) patients against Toxoplasma gondii is altered and whether this activity can be modulated by recombinant interferon-gamma (rIFN-gamma). Untreated and rIFN-gamma-treated monocytes or MDM from AIDS patients and from healthy controls were infected with T. gondii and the proliferation of these protozoa was determined. The H2O2 release by monocytes from AIDS patients and healthy controls was measured upon stimulation with phorbol myristate acetate (PMA) and formyl methionyl leucyl phenylalanine (FMLP). Monocytes from AIDS patients exhibited significantly lower toxoplasmastic activity compared to monocytes from healthy controls. The H2O2 release by monocytes from AIDS patients was also diminished. Incubation of monocytes from AIDS patients with rIFN-gamma for 2 days, but not 1 day, restored their toxoplasmastatic activity. The rate of proliferation of T. gondii was higher in MDM from AIDS patients than in MDM from healthy controls. Treatment of MDM from AIDS patients with rIFN-gamma for 1, 2 or 3 days resulted in partial inhibition of the proliferation of T. gondii. Collectively, these results demonstrate that the reduced toxoplasmastatic activity of monocytes and MDM from AIDS patients can be enhanced by in vitro treatment with rIFN-gamma, which supports the clinical use of rIFN-gamma for the treatment of opportunistic infections in these patients.

Delemarre, F G; Stevenhagen, A; Kroon, F P; van Eer, M Y; Meenhorst, P L; van Furth, R

1994-01-01

272

HIV-mediated immunodepression: in vitro inhibition of T-lymphocyte proliferative response by ultraviolet-inactivated virus  

SciTech Connect

In order to assess whether the human retrovirus HIV, like other animal retroviruses, is endowed with intrinsic immunosuppressive activity, we studied the effects of noninfectious, uv-irradiated virus on in vitro lymphocyte function. uvHIV preparations inhibited T-cell proliferation to mitogens and alloantigens, as well as mitogen-driven IL-2 production. The inhibitory effect, which was not exerted by uv-irradiated HTLV-I, was apparently not due to a decrease in cell viability and was likely associated with thermoresistant viral component(s). The suppression proved to be selective for T-cell responses, while sparing other lymphocyte functions, such as the B-cell proliferative response to a selective B-cell mitogen. The inhibitory effect of uvHIV was not counteracted by a substantial reduction in the number of monocytes or by indomethacin. Moreover, IL-1 production by monocytes was not affected upon virus incubation. On the other hand, the proliferative response of both CD4+ and CD8+ T-cell clones was inhibited by uvHIV, suggesting that T cells represent the actual target for the inhibitory effect. Although a sizeable decrease in IL-2 production was observed following uvHIV incubation, exogenous IL-2 was not capable of reversing the virus-induced suppression of the proliferation. The possibility that the immunosuppressive activity of noninfectious HIV contributes to the T-cell defect in infected patients by mechanisms other than the cytopathic effect on CD4+ T lymphocytes is discussed.

Amadori, A.; Faulkner-Valle, G.P.; De Rossi, A.; Zanovello, P.; Collavo, D.; Chieco-Bianchi, L.

1988-01-01

273

Virulence factors determine attachment and ingestion of nonopsonized and opsonized Bordetella pertussis by human monocytes.  

PubMed

In the present study, the role of virulence factors in and the effect of opsonization on the interactions between Bordetella pertussis and human monocytes were investigated. The methods used facilitated the distinction between attachment and ingestion of bacteria by monocytes. Nonopsonized virulent B. pertussis cells attached to monocytes. Nonopsonized B. pertussis mutant strains deficient in filamentous hemagglutinin, fimbriae, or pertactin exhibited a reduced adherence to monocytes compared with that of their respective parental strains. Nonopsonized avirulent B. pertussis cells did not attach to monocytes. These results led to the conclusion that fimbriae and pertactin are involved in the adherence of nonopsonized virulent B. pertussis cells to monocytes and confirm the role of filamentous hemagglutinin in this process. In the absence of opsonins, about 40% of the monocyte-associated virulent B. pertussis cells were ingested. When B. pertussis cells were preopsonized with inactivated normal serum, about 50% of the monocyte-associated virulent B. pertussis cells were phagocytosed and about 80% of the monocyte-associated avirulent B. pertussis cells were ingested. These results indicate that virulence factors inhibit opsonin-mediated ingestion of B. pertussis by monocytes. PMID:7927760

Hazenbos, W L; van den Berg, B M; van't Wout, J W; Mooi, F R; van Furth, R

1994-11-01

274

Virulence factors determine attachment and ingestion of nonopsonized and opsonized Bordetella pertussis by human monocytes.  

PubMed Central

In the present study, the role of virulence factors in and the effect of opsonization on the interactions between Bordetella pertussis and human monocytes were investigated. The methods used facilitated the distinction between attachment and ingestion of bacteria by monocytes. Nonopsonized virulent B. pertussis cells attached to monocytes. Nonopsonized B. pertussis mutant strains deficient in filamentous hemagglutinin, fimbriae, or pertactin exhibited a reduced adherence to monocytes compared with that of their respective parental strains. Nonopsonized avirulent B. pertussis cells did not attach to monocytes. These results led to the conclusion that fimbriae and pertactin are involved in the adherence of nonopsonized virulent B. pertussis cells to monocytes and confirm the role of filamentous hemagglutinin in this process. In the absence of opsonins, about 40% of the monocyte-associated virulent B. pertussis cells were ingested. When B. pertussis cells were preopsonized with inactivated normal serum, about 50% of the monocyte-associated virulent B. pertussis cells were phagocytosed and about 80% of the monocyte-associated avirulent B. pertussis cells were ingested. These results indicate that virulence factors inhibit opsonin-mediated ingestion of B. pertussis by monocytes.

Hazenbos, W L; van den Berg, B M; van't Wout, J W; Mooi, F R; van Furth, R

1994-01-01

275

Influence of GSM signals on human peripheral lymphocytes: study of genotoxicity.  

PubMed

Exposure to radiofrequency (RF) electromagnetic fields (EMF) is continuously increasing worldwide. Yet, conflicting results of a possible genotoxic effect of RF EMF continue to be discussed. In the present study, a possible genotoxic effect of RF EMF (GSM, 1,800 MHz) in human lymphocytes was investigated by a collaboration of six independent institutes (institutes a, b, c, d, e, h). Peripheral blood of 20 healthy, nonsmoking volunteers of two age groups (10 volunteers 16-20 years old and 10 volunteers 50-65 years old) was taken, stimulated and intermittently exposed to three specific absorption rates (SARs) of RF EMF (0.2 W/kg, 2 W/kg, 10 W/kg) and sham for 28 h (institute a). The exposures were performed in a setup with strictly controlled conditions of temperature and dose, and randomly and automatically determined waveguide SARs, which were designed and periodically maintained by ITIS (institute h). Four genotoxicity tests with different end points were conducted (institute a): chromosome aberration test (five types of structural aberrations), micronucleus test, sister chromatid exchange test and the alkaline comet assay (Olive tail moment and % DNA). To demonstrate the validity of the study, positive controls were implemented. The genotoxicity end points were evaluated independently by three laboratories blind to SAR information (institute c = laboratory 1; institute d = laboratory 2; institute e = laboratory 3). Statistical analysis was carried out by institute b. Methods of primary statistical analysis and rules to adjust for multiple testing were specified in a statistical analysis plan based on a data review before unblinding. A linear trend test based on a linear mixed model was used for outcomes of comet assay and exact permutation test for linear trend for all other outcomes. It was ascertained that only outcomes with a significant SAR trend found by at least two of three analyzing laboratories indicated a substantiated suspicion of an exposure effect. On the basis of these specifications, none of the nine end points tested for SAR trend showed a significant and reproducible exposure effect. Highly significant differences between sham exposures and positive controls were detected by each analyzing laboratory, thus validating the study. In conclusion, the results show no evidence of a genotoxic effect induced by RF EMF (GSM, 1,800 MHz). PMID:23316708

Waldmann, Petra; Bohnenberger, Susanne; Greinert, Rüdiger; Hermann-Then, Beate; Heselich, Anja; Klug, Stefanie J; Koenig, Jochem; Kuhr, Kathrin; Kuster, Niels; Merker, Mandy; Murbach, Manuel; Pollet, Dieter; Schadenboeck, Walter; Scheidemann-Wesp, Ulrike; Schwab, Britt; Volkmer, Beate; Weyer, Veronika; Blettner, Maria

2013-02-01

276

Comparative study of KL-6, surfactant protein-A, surfactant protein-D, and monocyte chemoattractant protein-1 as serum markers for interstitial lung diseases.  

PubMed

KL-6, surfactant protein (SP)-A, SP-D, and monocyte chemoattractant protein-1 (MCP-1) are reported to be sensitive markers for interstitial lung diseases (ILD). However, each marker has been studied independently. The aim of this study was a comparative analysis of the diagnostic values of these markers. Subjects consisted of 33 patients with ILD (21 cases of idiopathic pulmonary fibrosis and 12 associated with collagen vascular diseases) and 82 control subjects (12 cases of bacterial pneumonia and 70 healthy volunteers). Receiver operating characteristic curves revealed that KL-6 was superior to the other markers. The cut-off levels for these markers that resulted in the highest diagnostic accuracy were determined to be 465 U/ml for KL-6, 48.2 ng/ml for SP-A, 116 ng/ml for SP-D, and 1080 pg/ml for MCP-1. The sensitivity, specificity, and diagnostic accuracy were 93.9%, 96.3%, and 95.7% for KL-6; 81.8%, 86.6%, and 85.2% for SP-A; 69.7%, 95.1%, and 87.8% for SP-D; and 51.5%, 92.7%, and 80.9% for MCP-1; respectively. The serum levels of SP-A and SP-D, but not of KL-6, were significantly higher in patients with bacterial pneumonia than in healthy volunteers. These results suggest that of the markers studied, KL-6 is the best serum marker for ILD. PMID:11818324

Ohnishi, Hiroshi; Yokoyama, Akihito; Kondo, Keiichi; Hamada, Hironobu; Abe, Masahiro; Nishimura, Kazutaka; Hiwada, Kunio; Kohno, Nobuoki

2002-02-01

277

Microvesicular Caspase-1 Mediates Lymphocyte Apoptosis in Sepsis  

PubMed Central

Objective Immune dysregulation during sepsis is poorly understood, however, lymphocyte apoptosis has been shown to correlate with poor outcomes in septic patients. The inflammasome, a molecular complex which includes caspase-1, is essential to the innate immune response to infection and also important in sepsis induced apoptosis. Our group has recently demonstrated that endotoxin-stimulated monocytes release microvesicles (MVs) containing caspase-1 that are capable of inducing apoptosis. We sought to determine if MVs containing caspase-1 are being released into the blood during human sepsis and induce apoptosis.. Design Single-center cohort study Measurements 50 critically ill patients were screened within 24 hours of admission to the intensive care unit and classified as either a septic or a critically ill control. Circulatory MVs were isolated and analyzed for the presence of caspase-1 and the ability to induce lymphocyte apoptosis. Patients remaining in the ICU for 48 hours had repeated measurement of caspase-1 activity on ICU day 3. Main Results Septic patients had higher microvesicular caspase-1 activity 0.05 (0.04, 0.07) AFU versus 0.0 AFU (0, 0.02) (p<0.001) on day 1 and this persisted on day 3, 0.12 (0.1, 0.2) versus 0.02 (0, 0.1) (p<0.001). MVs isolated from septic patients on day 1 were able to induce apoptosis in healthy donor lymphocytes compared with critically ill control patients (17.8±9.2% versus 4.3±2.6% apoptotic cells, p<0.001) and depletion of MVs greatly diminished this apoptotic signal. Inhibition of caspase-1 or the disruption of MV integrity abolished the ability to induce apoptosis. Conclusion These findings suggest that microvesicular caspase-1 is important in the host response to sepsis, at least in part, via its ability to induce lymphocyte apoptosis. The ability of microvesicles to induce apoptosis requires active caspase-1 and intact microvesicles.

Exline, Matthew C.; Justiniano, Steven; Hollyfield, Jennifer L.; Berhe, Freweine; Besecker, Beth Y.; Das, Srabani; Wewers, Mark D.; Sarkar, Anasuya

2014-01-01

278

Oxidized Low Density Lipoprotein Induces Differentiation and Adhesion of Human Monocytes and the Monocytic Cell Line U937  

NASA Astrophysics Data System (ADS)

Hypercholesterolemia is a major risk factor for development of atherosclerosis. In experimental animals fed a high-cholesterol diet, monocytes adhere to the arterial endothelium and penetrate into the intima where they differentiate into macrophages and ingest lipids thus giving rise to fatty streaks, the earliest type of atherosclerotic plaque. Macrophages express few receptors for normal low density lipo-protein (LDL) but can take up oxidized LDL by way of a scavenger receptor. The present study was designed to investigate the possible role of oxidized LDL in recruitment of resident intimal macrophages. We found that oxidized LDL induced enhanced expression of major histocompatibility complex class II molecules on human monocytes and U937 cells, a well-established system for studies of monocytic differentiation. Oxidized LDL also induced enhanced expression of the surface antigen LEuM3 but caused decreased expression of CD4 antigen, a pattern compatible with expression of a more differentiated macrophage-like phenotype. Oxidized LDL also initiated aggregation of monocytes and U937 cells and stimulated adhesion of U937 cells to cultured endothelial cells. The results indicate that oxidized LDL may contribute to development of atherosclerosis by inducing adhesion of monocytes to the arterial intima and by stimulating intimal monocytes to differentiate into resident macrophages.

Frostegard, Johan; Nilsson, Jan; Haegerstrand, Anders; Hamsten, Anders; Wigzell, Hans; Gidlund, Magnus

1990-02-01

279

Comparative analysis of monocyte subsets in the pig.  

PubMed

Human and mouse monocyte can be divided into two different subpopulations based on surface marker expression: CD14/16 and Ly6C/CX3CR1, respectively. Monocyte subpopulations in the pig were identified based on reciprocal expression of CD14 and the scavenger receptor CD163. The two populations, CD14(hi)-CD163(low) and CD14(low)-CD163(hi), show approximately equal abundance in the steady-state. Culture of pig PBMCs in CSF1 indicates that the two populations are a maturation series controlled by this growth factor. Gene expression in pig monocyte subpopulations was profiled using the newly developed and annotated pig whole genome snowball microarray. Previous studies have suggested a functional equivalence between human and mouse subsets, but certain genes such as CD36, CLEC4E, or TREM-1 showed human-specific expression. The same genes were expressed selectively in pig monocyte subsets. However, the profiles suggest that the pig CD14(low)-CD163(high) cells are actually equivalent to intermediate human monocytes, and there is no CD14(-) CD16(+) "nonclassical" population. The results are discussed in terms of the relevance of the pig as a model for understanding human monocyte function. PMID:23667115

Fairbairn, Lynsey; Kapetanovic, Ronan; Beraldi, Dario; Sester, David P; Tuggle, Chris K; Archibald, Alan L; Hume, David A

2013-06-15

280

Astrocytic regulation of human monocytic/microglial activation.  

PubMed

Recent reports have described reduced immunological responsiveness and stimulatory capacity among monocytes/microglia that infiltrate malignant human gliomas. Herein, we demonstrate that culture of ex vivo human monocytes or primary human microglia with tumor cells isolated from glioblastoma multiforme (GBM) specimens renders them tolerogenic, capable of suppressing the function of ex vivo monocytes in the absence of tumor cells or their soluble factors. We demonstrate that the tolerance induced in monocytes/microglia by GBM tumor cells is not associated with interference with the signaling cascade associated with TLR- or CD40-induced monocyte activation. Rather, these tumor cells appear to up-regulate pathways that antagonize positive signaling pathways, including but not limited to STAT3 and STAT5. Finally, we demonstrate that the tolerogenic properties of GBM tumor cells amplify properties inherent to nontransformed astrocytes. Future studies that identify all of the molecular mechanisms by which astrocytes and malignant gliomas suppress monocyte/microglial function will have dual therapeutic benefits: suppressing these pathways may benefit patients with astrocytic tumors, while enhancing them may benefit patients with autoimmune processes within the CNS, such as multiple sclerosis. PMID:18832699

Kostianovsky, Alex M; Maier, Lisa M; Anderson, Richard C; Bruce, Jeffrey N; Anderson, David E

2008-10-15

281

Study of apoptosis in human lymphocytes by toxic substances implicated in toxic oil syndrome.  

PubMed

Toxic Oil Syndrome is a multisystemic disease that occurred in epidemic proportions in Spain in 1981 caused by the ingestion of rapeseed oil denatured with aniline. Several data implicate T cells in the pathogenesis of the disease. We evaluated the mechanisms of cytotoxicity in human lymphocytes of TOS-related products: aniline, 3-(N-phenylamino)-1,2-propanediol and its mono- and di-oleyl esters and eosinophilia myalgia-related product such as 3-(phenylamino)-L-alanine, which is chemically similar to 3-(N-phenylamino)-1,2-propanediol, and has been found in manufactured L-tryptophan. Our results show that only di-oleyl ester of 3-(N-phenylamino)-1,2-propanediol induces apoptosis in human lymphocytes, in a concentration and time-dependent way, confirmed by morphology, expression of phosphatidylserine in membrane and analysis of DNA degradation. PMID:9074655

Gallardo, S; Cárdaba, B; del Pozo, V; de Andrés, B; Cortegano, I; Jurado, A; Tramón, P; Palomino, P; Lahoz, C

1997-03-14

282

Inducibility of aryl hydrocarbon hydroxylase in cultured human lymphocytes: a study of repeatability.  

PubMed Central

Modifications to the method for estimating aryl hydrocarbon hydroxylase (AHH) activity in cultured human lymphocytes are described. Despite the improvements to the technique it was not possible to show significant 'repeatability' of values for AHH induction over a period of 2 weeks or more. Significant repeatability could be seen when a blood sample from each subject was split into duplicates. However, this level of repeatability was low when considered for quantitative genetics purposes. Possible reasons for the poor repeatability have been discussed.

Fletcher, K A; Evans, D A; Canning, M V

1978-01-01

283

Reverse genetic studies of the DNA damage response in the chicken B lymphocyte line DT40  

Microsoft Academic Search

In the ‘post-genome’ era, reverse genetics is one of the most informative and powerful means to investigate protein function. The chicken B lymphocyte line DT40 is widely used for reverse genetics because the cells have a number of advantages, including efficient gene targeting as well as a remarkably stable phenotype. Furthermore, the absence of functional p53 in DT40 cells enables

Mitsuyoshi Yamazoe; Eiichiro Sonoda; Helfrid Hochegger; Shunichi Takeda

2004-01-01

284

Lymphocyte reconstitution following allogeneic hematopoietic stem cell transplantation: a retrospective study including 148 patients  

Microsoft Academic Search

Here we investigated the influence of parameters known before hematopoietic stem cell transplantation (HSCT) as well as the relevance of graft-versus-host disease (GvHD) and cytomegalovirus (CMV) reactivation on post transplant lymphocyte reconstitution in 148 patients treated in our institution between 1996 and 2003. Median patient age was 42 (19–68) years, HSCT followed standard high dose (n=91) or reduced-intensity conditioning regimens

C Heining; A Spyridonidis; E Bernhardt; J Schulte-Mönting; D Behringer; C Grüllich; A Jakob; H Bertz; J Finke

2007-01-01

285

[Study of isoenzymes of lymphocyte populations during controlled immunization and in autoimmune pathology].  

PubMed

It has been shown that during immune system activation pronounced alterations are observed in the metabolic process course in lymphoid cells that, probably, reflect the changes in T- and B-lymphocyte functional activity, and the kinetics of intercellular relationships. The ratio of LDH1 and LDH5 fractions most differing in electrophoretic mobility has been recommended as a sign of B-system immunity activation. PMID:2210315

San'ko, N M; Kaliia, E S; Matve?kov, G P; Levin, V I

1990-07-01

286

Anthropometric Characteristics, Physical Activity, and Risk of Non-Hodgkin's Lymphoma Subtypes and B-Cell Chronic Lymphocytic Leukemia: A Prospective Study  

Microsoft Academic Search

Anthropometric characteristics, physical activity, and risk of non-Hodgkin's lymphoma, its subtypes, and B-cell chronic lymphocytic leukemia (B-CLL) were evaluated in a prospective cohort study of 37,931 Iowa women who were aged 55-69 years at baseline in 1986. Through 1998, 261 cases of non-Hodgkin's lymphoma (137 diffuse, 58 follicular, and 32 small lymphocytic lymphomas) and 63 cases of B-CLL were identified

James R. Cerhan; Carol A. Janney; Celine M. Vachon; Thomas M. Habermann; Neil E. Kay; John D. Potter; Thomas A. Sellers; Aaron R. Folsom

287

Novel biphasic role for lymphocytes revealed during resolving inflammation  

PubMed Central

Acute inflammation is traditionally described as the influx of polymorphonuclear leukocytes (PMNs) followed by monocyte-derived macrophages, leading to resolution. This is a classic view, and despite subpopulations of lymphocytes possessing innate immune-regulatory properties, seldom is their role in acute inflammation and its resolution discussed. To redress this we show, using lymphocyte-deficient RAG1?/? mice, that peritoneal T/B lymphocytes control PMN trafficking by regulating cytokine synthesis. Once inflammation ensues in normal mice, lymphocytes disappear in response to DP1 receptor activation by prostaglandin D2. However, upon resolution, lymphocytes repopulate the cavity comprising B1, natural killer (NK), ?/? T, CD4+/CD25+, and B2 cells. Repopulating lymphocytes are dispensable for resolution, as inflammation in RAG1?/? and wild-type mice resolve uniformly. However, repopulating lymphocytes are critical for modulating responses to superinfection. Thus, in chronic granulomatous disease using gp91phox?/? mice, not only is resolution delayed compared with wild-type, but there is a failure of lymphocyte re-appearance predisposing to exaggerated immune responses upon secondary challenge that is rescued by resolution-phase lymphocytes. In conclusion, as lymphocyte repopulation is also evident in human peritonitis, we hereby describe a transition in T/B cells from acute inflammation to resolution, with a central role in modulating the severity of early onset and orchestrating responses to secondary infection.

Rajakariar, Ravindra; Lawrence, Toby; Bystrom, Jonas; Hilliard, Mark; Colville-Nash, Paul; Bellingan, Geoff; Fitzgerald, Desmond; Yaqoob, Muhammad M.

2008-01-01

288

Cyclic Nucleotides and Phosphodiesterases in Monocytic Differentiation  

PubMed Central

Monocytes are immune cells that can differentiate into a number of cell types including macrophages, dendritic cells, and osteoclasts upon exposure to various cytokines. The phenotypes of these differentiated cells are highly heterogeneous and their differentiation can be affected by the cyclic nucleotides, 3?–5?-cyclic adenosine monophosphate (cAMP) and 3? –5?-cyclic guanosine monophosphate (cGMP). The intracellular levels of cAMP and cGMP are controlled through regulation of production by adenylyl and guanylyl cyclases and through degradation by cyclic nucleotide phosphodiesterases (PDEs). PDE inhibition and subsequent changes in cyclic nucleotide levels can alter the final phenotype of a differentiating monocyte with regards to surface marker expression, gene expression, or changes in secreted chemokine and cytokine levels. The differentiation process itself can also be either inhibited or augmented by changes in cyclic nucleotide levels, depending on the system being studied and the timing of cyclic nucleotide elevation. This chapter explores the effects of PDE inhibition and increases in cGMP and cAMP on monocytic differentiation into osteoclasts, dendritic cells, and macrophages.

Hertz, Angie L.

2014-01-01

289

CD69 is independently prognostic in chronic lymphocytic leukemia: a comprehensive clinical and biological profiling study  

PubMed Central

Background CD69 is expressed in several hemopoietic cells and is an early activation marker in chronic lymphocytic leukemia. Chronic lymphocytic leukemia is a clinically heterogeneous disease which needs novel prognostic parameters which can be easily and efficiently managed. Design and Methods We investigated CD69 by flow cytometry in a series of 417 patients affected by chronic lymphocytic leukemia and compared this to other biological and clinical prognosticators. Results CD69 was associated with Rai stages (P=0.00002), ?2-microglobulin (P=0.0005) and soluble CD23 (P<0.0001). CD69 and ZAP-70 (P=0.018) or CD38 (P=0.00015) or immunoglobulin variable heavy chain gene mutations (P=0.0005) were also significantly correlated. Clinically, CD69 positive chronic lymphocytic leukemias received chemotherapy more frequently (74%; P<0.0001), and presented a shorter duration of response after fludarabine plus rituximab (P=0.010) as well as shorter progression free survival and overall survival (P<0.0001). CD69 demonstrated true additive prognostic properties, since the CD69+ plus ZAP-70+ or CD38+ or immunoglobulin variable heavy chain gene unmutated patients had the worst progression free survival and overall survival (P<0.0001). Interestingly, low CD69 expression was necessary to correctly prognosticate the longer progression free survival of patients with a low tumor burden of ?2-microglobulin (P=0.002), of soluble CD23 (P=0.020), or of Rai stages 0-I (P=0.005). CD69 was confirmed to be an independent prognostic factor in multivariate analysis of progression free survival (P=0.017) and overall survival (P=0.039). Conclusions Our data indicate that CD69 is significantly correlated with poor clinical and biological prognostic factors and is confirmed to be an independent disease prognosticator. This supports its introduction in a routine laboratory assessment and, possibly, in a prognostic scoring system for chronic lymphocytic leukemia, after an adequate standardization process.

Del Poeta, Giovanni; Del Principe, Maria Ilaria; Zucchetto, Antonella; Luciano, Fabrizio; Buccisano, Francesco; Maria Rossi, Francesca; Bruno, Antonio; Biagi, Annalisa; Bulian, Pietro; Maurillo, Luca; Neri, Benedetta; Bomben, Riccardo; Simotti, Cristina; Coletta, Angela Maria; Dal Bo, Michele; de Fabritiis, Paolo; Venditti, Adriano; Gattei, Valter; Amadori, Sergio

2012-01-01

290

Human Cytomegalovirus Subverts the Functions of Monocytes, Impairing Chemokine-Mediated Migration and Leukocyte Recruitment  

PubMed Central

Despite their role in innate and adaptive immunity, during human cytomegalovirus (HCMV) infection, monocytes are considered to be an important target of infection, a site of latency, and vehicles for virus dissemination. Since chemokine receptors play crucial roles in monocyte activation and trafficking, we investigated the effects of HCMV on their expression and function. By using endotheliotropic strains of HCMV, we obtained high rates (roughly 50%) of in vitro-infected monocytes but only restricted viral gene expression. At 24 h after infection, while the chemokine receptors CX3CR and CCR7 were unaffected, CCR1, CCR2, CCR5, and CXCR4 were downmodulated on the cell surface and retained intracellularly. Structural components of the viral particles, but not viral gene expression or soluble factors released from infected cells, accounted for the changed localization of the receptor molecules and for the block of chemokine-driven migration. HCMV-infected monocytes indeed became unresponsive to inflammatory and homeostatic chemokines, although the basal cell motility and responsiveness to N-formyl-Met-Leu-Phe were unaffected or slightly increased. The production of inflammatory mediators responsible for the recruitment of other immune cells was also hampered by HCMV. Whereas endothelial and fibroblast cells infected by HCMV efficiently recruited leukocytes, infected monocytes were unable to recruit lymphocytes, monocytes, and neutrophils. Our data further highlight the complex level of interference exerted by HCMV on the host immune system.

Frascaroli, Giada; Varani, Stefania; Moepps, Barbara; Sinzger, Christian; Landini, Maria Paola; Mertens, Thomas

2006-01-01

291

SLC11A1 is expressed by innate lymphocytes and augments their activation1  

PubMed Central

SLC11A1 is a divalent ion transporter formerly known as the natural resistance-associated macrophage protein (NRAMP1) and the Bcg/Lsh/Ity locus. SLC11A1 was thought to be exclusively expressed in monocyte/macrophages and to have roles in phagosome maturation and cell activation. We characterized the expression of SLC11A1 in the majority of human and bovine ?? T cells and NK cells, and in human CD3+CD45RO+ T cells. Consistent with a role for iron-dependent inhibition of protein tyrosine phosphatases, SLC11A1+ lymphocytes were moreprone to activation and retained tyrosine phosphorylation. Transfection of SLC11A1 into a human ?? T cell-like line rendered the cells more prone to activation. Non-adherent splenocytes from wild type mice expressed significantly greater IFN-? compared to cells from Sv/129 (SLC11A1?/?) mice. Our data suggest that SLC11A1 has a heretofore unknown role in activation of a large subset of innate lymphocytes that are critical sources of IFN-?. SLC11A1+ animals have enhanced innate IFN-? expression in response to Salmonella infection compared to SLC11A1?mice, which includes commonly used inbred laboratory mice. Expression of SLC11A1 in innate lymphocytes and its role in augmenting their activation may account for inconsistencies in studies of innate lymphocytes in different animal models.

Hedges, Jodi F.; Kimmel, Emily; Snyder, Deann T.; Jerome, Maria; Jutila, Mark A.

2013-01-01

292

Association of Blood Monocyte and Platelet Markers with Carotid Artery Characteristics: The Atherosclerosis Risk in Communities Carotid MRI Study  

Microsoft Academic Search

Background: Atherosclerosis is characterized by infiltration of inflammatory cells from circulating blood. Blood cell activation could play an important role in plaque formation. Methods: We analyzed the relationship between blood cellular markers and quantitative measures of carotid wall components in 1,546 participants from the ARIC (Atherosclerosis Risk in Communities) Carotid MRI Study. Carotid imaging was performed using a gadolinium contrast-enhanced

N. Matijevic; K. K. Wu; A. G. Howard; B. Wasserman; W. Y.-W. Wang; A. R. Folsom; A. R. Sharrett

2011-01-01

293

Comparative study on cytogenetic effects by diplatinum complexes of the ligands of naphthazarine and squaric acid in human lymphocytes.  

PubMed

The effect of diplatinum complexes of the binucleating ligands of naphthazarine and squaric acid on Sister Chromatid Exchange (SCE) rates and human lymphocyte proliferation kinetics was studied. Squarodicisplatinum complex I, naphthazarindicisplatinum and squarodicisplatinum complex II induce cytotoxic effects as can be deduced from the resulted induction of SCEs and the produced cell division delays. Squarodicisplatinum complex I was found to be on a molar basis the most effective in causing markedly increased SCE rates and cell division delays. Cis-diaminodichloride platinum was found to be next in order of effectiveness with naphthazarindicisplatinum and squarodicisplatinum complex II following. Naphthazarine and SQA were found to be ineffective on induction of SCEs. PMID:2795466

Lialiaris, T; Mourelatos, D; Boutis, L; Papageorgiou, A; Christianopoulou, M; Papageorgiou, V; Dozi-Vassiliades, J

1989-10-01

294

The cellular origin of the lymphocyte trap  

PubMed Central

We investigated the cellular requirements for lymphocyte trapping. Depletion of lymphocyte populations selectively or indiscriminately did not affect the ability of animals to trap. The variety of materials which initiate trapping was also studied and this information, coupled with the resistance of `trapping' to severe lymphocyte depletion, is consistent with the hypothesis that the macrophage may be the central cell in initiating the trapping of lymphocytes after antigen stimulation.

Frost, P.; Lance, E. M.

1974-01-01

295

[Effects of propham and chloropropham on mitosis in cultured human lymphocytes. Ultrastructural study].  

PubMed

Propham and Chloropropham disturb the several mitotic figure components of proliferating human lymphocytes. The tubular structures, affected in preference by the C.I.P.C., become abnormal, disorganized or disappear. The chromosomal changes (protuberances,absence of condensation and chromosomal bridges) are principally given by I.P.C. I.P.C. and C.I.P.C. lead to the disappearance of the endoplasmic reticulum. These effects are correlated with the action of the two pesticides on DNA and protein synthesis. PMID:6446961

Michel, R; Tournamille, J; Caporiccio, B; Sentein, P

1980-01-01

296

[Studies on the effect of an alkaloid extract of Symphytum officinale on human lymphocyte cultures].  

PubMed

An alkaloid extract of Symphytum officinale was investigated for its chromosome-damaging effect in human lymphocytes in vitro. In concentrations of 1.4 micrograms/ml and 14 micrograms/ml the alkaloids had no effect, in concentrations of 140 micrograms/ml and 1400 micrograms/ml the alkaloids induced sister chromatid exchanges (SCE) as well as chromosome aberrations. Additionally, the influence of rat liver enzymes (S9) was tested. The SCE-inducing capacity and the clastogenic effect of Symphytum alkaloids was increased by simultaneous application of S9-Mix. PMID:2616671

Behninger, C; Abel, G; Röder, E; Neuberger, V; Göggelmann, W

1989-12-01

297

Manganese supplementation reduces high glucose-induced monocyte adhesion to endothelial cells and endothelial dysfunction in Zucker diabetic fatty rats.  

PubMed

Endothelial dysfunction is a hallmark of increased vascular inflammation, dyslipidemia, and the development of atherosclerosis in diabetes. Previous studies have reported lower levels of Mn(2+) in the plasma and lymphocytes of diabetic patients and in the heart and aortic tissue of patients with atherosclerosis. This study examines the hypothesis that Mn(2+) supplementation can reduce the markers/risk factors of endothelial dysfunction in type 2 diabetes. Human umbilical vein endothelial cells (HUVECs) were cultured with or without Mn(2+) supplementation and then exposed to high glucose (HG, 25 mm) to mimic diabetic conditions. Mn(2+) supplementation caused a reduction in monocyte adhesion to HUVECs treated with HG or MCP-1. Mn(2+) also inhibited ROS levels, MCP-1 secretion, and ICAM-1 up-regulation in HUVECs treated with HG. Silencing studies using siRNA against MnSOD showed that similar results were observed in MnSOD knockdown HUVECs following Mn(2+) supplementation, suggesting that the effect of manganese on monocyte adhesion to endothelial cells is mediated by ROS and ICAM-1, but not MnSOD. To validate the relevance of our findings in vivo, Zucker diabetic fatty rats were gavaged daily with water (placebo) or MnCl2 (16 mg/kg of body weight) for 7 weeks. When compared with placebo, Mn(2+)-supplemented rats showed lower blood levels of ICAM-1 (17%, p < 0.04), cholesterol (25%, p < 0.05), and MCP-1 (28%, p = 0.25). These in vitro and in vivo studies demonstrate that Mn(2+) supplementation can down-regulate ICAM-1 expression and ROS independently of MnSOD, leading to a decrease in monocyte adhesion to endothelial cells, and therefore can lower the risk of endothelial dysfunction in diabetes. PMID:23329836

Burlet, Elodie; Jain, Sushil K

2013-03-01

298

Dietary omega-3, omega-6, and omega-9 unsaturated fatty acids and growth factor and cytokine gene expression in unstimulated and stimulated monocytes. A randomized volunteer study.  

PubMed

Dietary omega-3 fatty acids retard coronary atherosclerosis. Previously, we demonstrated that dietary omega-3 fatty acids reduce platelet-derived growth factor (PDGF)-A and PDGF-B mRNA levels in unstimulated, human mononuclear cells (MNCs). In a randomized, investigator-blinded intervention trial, we have now compared the effect of ingestion of 7 g/d omega-3, omega-6, or omega-9 fatty acids for 4 weeks versus no dietary intervention on PDGF-A, PDGF-B, heparin-bound epidermal growth factor (HB-EGF), monocyte chemoattractant protein-1 (MCP-1), and interleukin-10 gene expression in unstimulated MNCs and in monocytes that were adherence-activated ex vivo in a total of 28 volunteers. In unstimulated MNCs, mRNA steady-state levels of PDGF-A, PDGF-B, and MCP-1 were reduced by 25+/-10%, 31+/-13%, and 40+/-14%, respectively, after omega-3 fatty acid ingestion, as assessed by quantitative polymerase chain reaction (all P<0.05). In monocytes that were adherence-activated ex vivo for 4 and 20 hours, mRNA steady-state levels of PDGF-A, PDGF-B, and MCP-1 were reduced by 25+/-13%, 20+/-15%, and 30+/-8%, respectively (all P<0.05). Interleukin-10 and HB-EGF mRNA steady-state levels were not influenced by omega-3 fatty acid ingestion. Expression of all respective mRNAs in control volunteers or in those ingesting omega-6 or omega-9 fatty acids were not altered. We conclude that human gene expression for PDGF-A, PDGF-B, and MCP-1, factors thought relevant to atherosclerosis, is constitutive, is constant, and can be reduced only by dietary omega-3 fatty acids in unstimulated and adherence-activated monocytes. PMID:9888867

Baumann, K H; Hessel, F; Larass, I; Müller, T; Angerer, P; Kiefl, R; von Schacky, C

1999-01-01

299

Altered cytokine gene expression in peripheral blood monocytes across the menstrual cycle in primary dysmenorrhea: a case-control study.  

PubMed

Primary dysmenorrhea is one of the most common gynecological complaints in young women, but potential peripheral immunologic features underlying this condition remain undefined. In this paper, we compared 84 common cytokine gene expression profiles of peripheral blood mononuclear cells (PBMCs) from six primary dysmenorrheic young women and three unaffected controls on the seventh day before (secretory phase), and the first (menstrual phase) and the fifth (regenerative phase) days of menstruation, using a real-time PCR array assay combined with pattern recognition and gene function annotation methods. Comparisons between dysmenorrhea and normal control groups identified 11 (nine increased and two decreased), 14 (five increased and nine decreased), and 15 (seven increased and eight decreased) genes with ? 2-fold difference in expression (P<0.05) in the three phases of menstruation, respectively. In the menstrual phase, genes encoding pro-inflammatory cytokines (IL1B, TNF, IL6, and IL8) were up-regulated, and genes encoding TGF-? superfamily members (BMP4, BMP6, GDF5, GDF11, LEFTY2, NODAL, and MSTN) were down-regulated. Functional annotation revealed an excessive inflammatory response and insufficient TGF-? superfamily member signals with anti-inflammatory consequences, which may directly contribute to menstrual pain. In the secretory and regenerative phases, increased expression of pro-inflammatory cytokines and decreased expression of growth factors were also observed. These factors may be involved in the regulation of decidualization, endometrium breakdown and repair, and indirectly exacerbate primary dysmenorrhea. This first study of cytokine gene expression profiles in PBMCs from young primary dysmenorrheic women demonstrates a shift in the balance between expression patterns of pro-inflammatory cytokines and TGF-? superfamily members across the whole menstrual cycle, underlying the peripheral immunologic features of primary dysmenorrhea. PMID:23390521

Ma, Hongyue; Hong, Min; Duan, Jinao; Liu, Pei; Fan, Xinsheng; Shang, Erxin; Su, Shulan; Guo, Jianming; Qian, Dawei; Tang, Yuping

2013-01-01

300

Familial Chronic Lymphocytic Leukemia.  

National Technical Information Service (NTIS)

Chronic lymphocytic leukemia (CLL) was previously documented in a father and 4 of his offspring. Follow-up studies revealed spontaneous regression of the disease in 1 patient and shifts in the clinical patterns in other patients; the unaffected sibling de...

C. Y. Neuland W. A. Blattner D. L. Mann M. C. Fraser S. Tsai

1983-01-01

301

Isolation and functional studies of granulated lymphocytes in first trimester human decidua.  

PubMed Central

Granulated lymphoid cells (CD2+, CD7+, CD38+, NKH1+, CD3-, CD5-, CD4-, CD8-, CD25-) are prominent in human endometrial stroma in the late secretory phase of the menstrual cycle and in early pregnancy, and may play an important role in implantation and placentation. Cell suspensions enriched for granulated lymphoid cells were prepared from first trimester human decidua using a panning technique; cells were labelled with the monoclonal antibody NKH1 and separated by adherence to immunoglobulin-coated plates. The enriched cells were characterized with a panel of monoclonal antibodies using an indirect immuno-alkaline phosphatase method, and subjected to various functional assays. Most cells in the enriched preparations showed the characteristic morphology of granulated lymphocytes in smears stained with toluidine blue or May Grunwald Giemsa. CD45+ cells were obtained up to 98 +/- 1% purity (n = 10) and CD2+ cells were enriched up to 84 +/- 4%. The enriched populations were efficient effectors in a K562 chromium-release assay but showed minimal proliferative response to phytohaemagglutinin, concanavalin A, ionomycin and phorbol 12, 13 dibutyrate (PdBU), interleukin 1 or interleukin 2. The precise lineage and in vivo function of decidual granulated lymphocytes remains to be established.

Ritson, A; Bulmer, J N

1989-01-01

302

In vitro studies of poison oak immunity. I. In vitro reaction of human lymphocytes to urushiol.  

PubMed Central

Poison oak, ivy, and sumac dermatitis is a T-cell-mediated reaction against urushiol, the oil found in the leaf of the plants. This hapten is extremely lipophilic and concentrates in cell membranes. A blastogenesis assay employing peripheral blood lymphocytes obtained from humans sensitized to urushiol is described. The reactivity appears 1--3 wk after exposure and persists from 6 wk to 2 mon. The dose-response range is narrow, with inhibition occurring at higher antigen concentrations. Urushiol introduced into the in vitro culture on autologous lymphocytes, erythrocytes and heterologous erythrocytes produces equal results as measured by the optimal urushiol dose, the intensity of reaction, and the frequency of positive reactors. This suggests that the urushiol is passed from introducer to some other presenter cell. Although the blastogenically reactive cell is a T cell, there is also a requirement for an accessory cell, found in the non-T-cell population, for reactivity. Evidence is presented that this cell is a macrophage.

Byers, V S; Epstein, W L; Castagnoli, N; Baer, H

1979-01-01

303

Ber-MAC3: new monoclonal antibody that defines human monocyte/macrophage differentiation antigen.  

PubMed Central

A new monoclonal antibody Ber-MAC3 is reported. It recognises a formol sensitive epitope of a not yet clustered monocyte/macrophage specific 140 kilodalton glycoprotein that is expressed on the cell surface and in the cytoplasm. In 30 cases of acute and chronic leukaemia, Ber-MAC3 staining was restricted to 15 myeloid leukaemias of M4 and M5 types. The tumour cells of two cases of true histiocytic malignancies were Ber-MAC3 positive, whereas those of all 280 malignancies of lymphocytic origin were negative. The latter included 52 cases of Hodgkin's disease and 41 cases of Ki-1 positive anaplastic large cell lymphomas which had previously been classified as true histiocytic lymphomas. Ber-MAC3 therefore seems to be of considerable value for selective identification of monocytes and macrophages at a certain stage of differentiation and seems to be suitable for diagnosing myelomonocytic or monocytic leukaemia and neoplasms of true histiocytic origin. Images

Backe, E; Schwarting, R; Gerdes, J; Ernst, M; Stein, H

1991-01-01

304

Carcinoma origin dictates differential skewing of monocyte function  

PubMed Central

Macrophages are versatile cells, which phenotype is profoundly influenced by their environment. Pro-inflammatory classically activated or M1 macrophages, and anti-inflammatory alternatively-activated or M2 macrophages represent two extremes of a continuum of functional states. Consequently, macrophages that are present in tumors can exert tumor-promoting and tumor-suppressing activity, depending on the tumor milieu. In this study we investigated how human monocytes—the precursors of macrophages—are influenced by carcinoma cells of different origin. We demonstrate that monocytes, stimulated with breast cancer supernatant, showed increased expression of interleukin (IL)-10, IL-8 and chemokines CCL17 and CCL22, which are associated with an alternatively-activated phenotype. By contrast, monocytes that were cultured in supernatants of colon cancer cells produced more pro-inflammatory cytokines (e.g., IL-12 and TNF?) and reactive oxygen species. Secretome analysis revealed differential secretion of proteins by colon and breast cancer cell lines, of which the proteoglycan versican was exclusively secreted by colon carcinoma cell lines. Reducing active versican by blocking with monoclonal antibodies or shRNA diminished pro-inflammatory cytokine production by monocytes. Thus, colon carcinoma cells polarize monocytes toward a more classically-activated anti-tumorigenic phenotype, whereas breast carcinomas predispose monocytes toward an alternatively activated phenotype. Interestingly, presence of macrophages in breast or colon carcinomas correlates with poor or good prognosis in patients, respectively. The observed discrepancy in macrophage activation by either colon or breast carcinoma cells may therefore explain the dichotomy between patient prognosis and macrophage presence in these different tumors. Designing new therapies, directing development of monocytes toward M1 activated tumor macrophages in cancer patients, may have great clinical benefits.

Bogels, Marijn; Braster, Rens; Nijland, Philip G.; Gul, Nuray; van de Luijtgaarden, Wendy; Fijneman, Remond J.A.; Meijer, Gerrit A.; Jimenez, Connie R.; Beelen, Robert H.J.; van Egmond, Marjolein

2012-01-01

305

Identification of a human peripheral blood monocyte subset that differentiates into osteoclasts  

PubMed Central

Increased bone resorption mediated by osteoclasts causes various diseases such as osteoporosis and bone erosion in rheumatoid arthritis (RA). Osteoclasts are derived from the monocyte/macrophage lineage, but the precise origin remains unclear. In the present study, we show that the purified CD16- human peripheral blood monocyte subset, but not the CD16+ monocyte subset, differentiates into osteoclast by stimulation with receptor activator of NF-?B ligand (RANKL) in combination with macrophage colony-stimulating factor (M-CSF). Integrin-?3 mRNA and the integrin-?v?3 heterodimer were only expressed on CD16- monocytes, when they were stimulated with RANKL + M-CSF. Downregulation of ?3-subunit expression by small interfering RNA targeting ?3 abrogated osteoclastogenesis from the CD16- monocyte subset. In contrast, the CD16+ monocyte subset expressed larger amounts of tumor necrosis factor alpha and IL-6 than the CD16- subset, which was further enhanced by RANKL stimulation. Examination of RA synovial tissue showed accumulation of both CD16+ and CD16- macrophages. Our results suggest that peripheral blood monocytes consist of two functionally heterogeneous subsets with distinct responses to RANKL. Osteoclasts seem to originate from CD16- monocytes, and integrin ?3 is necessary for osteoclastogenesis. Blockade of accumulation and activation of CD16- monocytes could therefore be a beneficial approach as an anti-bone resorptive therapy, especially for RA.

Komano, Yukiko; Nanki, Toshihiro; Hayashida, Kenji; Taniguchi, Ken; Miyasaka, Nobuyuki

2006-01-01

306

Microwell Devices with Finger-like Channels for Long-Term Imaging of HIV-1 Expression Kinetics in Primary Human Lymphocytes  

PubMed Central

A major obstacle in the treatment of human immunodeficiency virus type 1 (HIV-1) is a sub-population of latently infected CD4+ T lymphocytes. The cellular and viral mechanisms regulating HIV-1 latency are not completely understood, and a promising technique for probing the regulation of HIV-1 latency is single-cell time-lapse microscopy. Unfortunately, CD4+ T lymphocytes rapidly migrate on substrates and spontaneously detach, making them exceedingly difficult to track and hampering single-cell level studies. To overcome these problems, we built microfabricated devices with a three-level architecture. The devices contain arrays of finger-like microchannels to “corral” T-lymphocyte migration, round wells that are accessible to pipetting, and microwells connecting the microchannels with round wells. T lymphocytes that are loaded into a well first settle into the microwells and then to microchannels by gravity. Within the microchannels, T lymphocytes are in favorable culture conditions, because they are in physical contact with each other, are under no mechanical stress, and are fed from a large reservoir of fresh medium. Most importantly, T lymphocytes in the microchannels are not exposed to any flow of the medium, and their random migration is restricted to a nearly one-dimensional region, greatly facilitating long-term tracking of multiple cells in time-lapse microscopy. The devices have up to nine separate round wells, making it possible to test up to nine different cell lines or medium conditions in a single experiment. Activated primary CD4+ T lymphocytes, resting primary CD4+ T lymphocytes, and THP-1 monocytic leukemia cells loaded into the devices maintained viability over multiple days. The devices were used to track the fluorescence level of individual primary CD4+ T lymphocytes expressing green fluorescent protein (GFP) for up to 60 hours and to quantify single-cell gene-expression kinetics of four different HIV-1 variants in primary human CD4+ T lymphocytes. The kinetics of GFP expression from the lentiviruses in the primary CD4+ T lymphocytes agree with previous measurements of these lentiviral vectors in the immortalized Jurkat T lymphocyte cell line. These devices offer a simple, robust approach to long-term single-cell studies of environmentally sensitive primary lymphocytes.

Razooky, Brandon; Gutierrez, Edgar; Terry, Valeri H.; Spina, Celsa A.; Groisman, Alex; Weinberger, Leor

2013-01-01

307

Carbon Black Particle Exhibits Size Dependent Toxicity in Human Monocytes  

PubMed Central

Increased levels of particulate air pollution are associated with increased respiratory and cardiovascular mortality and morbidity. Some epidemiologic and toxicological researches suggest ultrafine particles (<100?nm) to be more harmful per unit mass than larger particles. In the present study, the effect of particle size (nano and micro) of carbon black (CB) particle on viability, phagocytosis, cytokine induction, and DNA damage in human monocytes, THP-1 cells, was analysed. The cells were incubated with nanosize (~50?nm) and micron (~500?nm) size of CB particles in a concentration range of 50–800?µg/mL. The parameters like MTT assay, phagocytosis assay, ELISA, gene expression, and DNA analysis were studied. Exposure to nano- and micron-sized CB particles showed size- and concentration dependent decrease in cell viability and significant increase in proinflammatory cytokines IL-1?, TNF-? and IL-6 as well as chemokine IL-8 release. Gene expression study showed upregulation of monocyte chemoattractant protein-1 gene while cyclooxygenase-2 gene remained unaffected. Nano CB particles altered the phagocytic capacity of monocytes although micron CB had no significant effect. CB particles did not show any significant effect on DNA of monocytes. The investigations indicate that CB particles in nanosize exhibit higher propensity of inducing cytotoxicity, inflammation, and altered phagocytosis in human monocytes than their micron size.

Kannan, G. M.; Vijayaraghavan, R.

2014-01-01

308

LAMP2 as a marker of EBV-mediated B lymphocyte transformation in the study of lysosomal storage diseases.  

PubMed

Following the degradative pathway, vesicles loaded with extracellular material, eventually, dock and fuse with lysosomes, acquiring specific membrane markers of these organelles and acid hydrolases responsible for digest their content. The lysosomal-associated membrane protein 2 (LAMP-2), the best characterized lysosomal membrane protein, is found in late stages of endosome maturation and may be used as a marker of lysosome-associated membranes. Lysosomal storage disorders (LSDs) are described by the absence or deficiency in hydrolase activity leading to substrate accumulation within lysosomal components and to the onset of several diseases. It is known that lymphocytes infected by Epstein-Barr virus (EBV) are able to form cytoplasmic vacuoles, which work as a storage compartment for lysosomal acidic hydrolases. At the present study, we validate the EBV as a transforming agent of B lymphocytes in stability studies of long-term stored samples, since the methods used to keep samples in liquid nitrogen and thaw them have all proven to be efficient in samples frozen for up to 2 years. To confirm and investigate some of the most prevalent LSDs in the South of Brazil-Pompe, Fabry and Gaucher diseases-we first measured the enzymatic activity of ?-glicosidase, ?-galactosidase, and ?-glicosidase in those cytoplasmic-formed vacuoles and then looked to LAMP-2 immunoreactivity by employing confocal microscopy techniques. PMID:24068328

Mello, A S; Goldim, M P; Mezzalira, J; Garcia, C S; Daitz, V V; Castilhos, C D; Viegas, M S; Vieira, O V; Coelho, J C

2014-01-01

309

Human Monocyte-Derived Dendritic Cells Exposed to Microorganisms Involved in Hypersensitivity Pneumonitis Induce a Th1-Polarized Immune Response  

PubMed Central

Hypersensitivity pneumonitis (HP) is an immunoallergic disease characterized by a prominent interstitial infiltrate composed predominantly of lymphocytes secreting inflammatory cytokines. Dendritic cells (DCs) are known to play a pivotal role in the lymphocytic response. However, their cross talk with microorganisms that cause HP has yet to be elucidated. This study aimed to investigate the initial interactions between human monocyte-derived DCs (MoDCs) and four microorganisms that are different in nature (Saccharopolyspora rectivirgula [actinomycetes], Mycobacterium immunogenum [mycobacteria], and Wallemia sebi and Eurotium amstelodami [filamentous fungi]) and are involved in HP. Our objectives were to determine the cross talk between MoDCs and HP-causative agents and to determine whether the resulting immune response varied according to the microbial extract tested. The phenotypic activation of MoDCs was measured by the increased expression of costimulatory molecules and levels of cytokines in supernatants. The functional activation of MoDCs was measured by the ability of MoDCs to induce lymphocytic proliferation and differentiation in a mixed lymphocytic reaction (MLR). E. amstelodami-exposed (EA) MoDCs expressed higher percentages of costimulatory molecules than did W. sebi-exposed (WS), S. rectivirgula-exposed (SR), or M. immunogenum-exposed (MI) MoDCs (P < 0.05, Wilcoxon signed-rank test). EA-MoDCs, WS-MoDCs, SR-MoDCs, and MI-MoDCs induced CD4+ T cell proliferation and a Th1-polarized immune response. The present study provides evidence that, although differences were initially observed between MoDCs exposed to filamentous fungi and MoDCs exposed to bacteria, a Th1 response was ultimately promoted by DCs regardless of the microbial extract tested.

Pallandre, Jean-Rene; Borg, Christophe; Loeffert, Sophie; Gbaguidi-Haore, Houssein; Millon, Laurence

2013-01-01

310

Hypoxia-inducible C-to-U coding RNA editing downregulates SDHB in monocytes  

PubMed Central

Background. RNA editing is a post-transcriptional regulatory mechanism that can alter the coding sequences of certain genes in response to physiological demands. We previously identified C-to-U RNA editing (C136U, R46X) which inactivates a small fraction of succinate dehydrogenase (SDH; mitochondrial complex II) subunit B gene (SDHB) mRNAs in normal steady-state peripheral blood mononuclear cells (PBMCs). SDH is a heterotetrameric tumor suppressor complex which when mutated causes paraganglioma tumors that are characterized by constitutive activation of hypoxia inducible pathways. Here, we studied regulation, extent and cell type origin of SDHB RNA editing. Methods. We used short-term cultured PBMCs obtained from random healthy platelet donors, performed monocyte enrichment by cold aggregation, employed a novel allele-specific quantitative PCR method, flow cytometry, immunologic cell separation, gene expression microarray, database analysis and high-throughput RNA sequencing. Results. While the editing rate is low in uncultured monocyte-enriched PBMCs (average rate 2.0%, range 0.4%–6.3%, n = 42), it is markedly upregulated upon exposure to 1% oxygen tension (average rate 18.2%, range 2.8%–49.4%, n = 14) and during normoxic macrophage differentiation in the presence of serum (average rate 10.1%, range 2.7%–18.8%, n = 17). The normoxic induction of SDHB RNA editing was associated with the development of dense adherent aggregates of monocytes in culture. CD14-positive monocyte isolation increased the percentages of C136U transcripts by 1.25-fold in normoxic cultures (n = 5) and 1.68-fold in hypoxic cultures (n = 4). CD14-negative lymphocytes showed no evidence of SDHB editing. The SDHB genomic DNA remained wild-type during increased RNA editing. Microarray analysis showed expression changes in wound healing and immune response pathway genes as the editing rate increased in normoxic cultures. High-throughput sequencing of SDHB and SDHD transcripts confirmed the induction of C136U RNA editing in normoxic cultures but showed no additional verifiable coding edits. Analysis of SDHB RNA sequence data from 16 normal human tissues from the Illumina Body Map and from 45 samples representing 23 different cell types from the ENCODE projects confirmed the occurrence of site-specific C136U editing in whole blood (1.7%) and two primary CD14+ monocyte samples (1.9% and 2.6%). In contrast, the other cell types showed an average of 0.2% and 0.1% C136U editing rates in the two databases, respectively. Conclusions. These findings demonstrate that C-to-U coding RNA editing of certain genes is dynamically induced by physiologically relevant environmental factors and suggest that epigenetic downregulation of SDHB by site-specific RNA editing plays a role in hypoxia adaptation in monocytes.

De Jong, Kitty; Liu, Biao; Wang, Jianmin; Patnaik, Santosh K.; Wallace, Paul K.; Taggart, Robert T.

2013-01-01

311

Monocyte recruitment during infection and inflammation.  

PubMed

Monocytes originate from progenitors in the bone marrow and traffic via the bloodstream to peripheral tissues. During both homeostasis and inflammation, circulating monocytes leave the bloodstream and migrate into tissues where, following conditioning by local growth factors, pro-inflammatory cytokines and microbial products, they differentiate into macrophage or dendritic cell populations. Recruitment of monocytes is essential for effective control and clearance of viral, bacterial, fungal and protozoal infections, but recruited monocytes also contribute to the pathogenesis of inflammatory and degenerative diseases. The mechanisms that control monocyte trafficking under homeostatic, infectious and inflammatory conditions are being unravelled and are the focus of this Review. PMID:21984070

Shi, Chao; Pamer, Eric G

2011-11-01

312

Monocyte recruitment during infection and inflammation  

PubMed Central

Monocytes originate from progenitors in the bone marrow and traffic via the bloodstream to peripheral tissues. During both homeostasis and inflammation, circulating monocytes leave the bloodstream and migrate into tissues where, following conditioning by local growth factors, pro-inflammatory cytokines and microbial products, they differentiate into macrophage or dendritic cell populations. Recruitment of monocytes is essential for effective control and clearance of viral, bacterial, fungal and protozoal infections, but recruited monocytes also contribute to the pathogenesis of inflammatory and degenerative diseases. The mechanisms that control monocyte trafficking under homeostatic, infectious and inflammatory conditions are being unravelled and are the focus of this Review.

Shi, Chao; Pamer, Eric G.

2014-01-01

313

HLA-F is a surface marker on activated lymphocytes.  

PubMed

Of the three nonclassical class I antigens expressed in humans, HLA-F has been least characterized with regard to expression or function. In this study, we examined HLA-F expression focusing on lymphoid cells, where our previous work with homologous cell lines had demonstrated surface HLA-F expression. HLA-F protein expression was observed by Western blot analysis in all resting lymphocytes, including B cells, T cells, NK cells, and monocytes, all of which lacked surface expression in the resting state. Upon activation, using a variety of methods to activate different lymphocyte subpopulations, all cell types that expressed HLA-F intracellularly showed an induction of surface HLA-F protein. An examination of peripheral blood from individuals genetically deficient for TAP and tapasin expression demonstrated the same activation expression profiles for HLA-F,but with altered kinetics post-activation. Further analysis of CD41+CD25+1 Treg showed that HLA-F was not upregulated on the major fraction of these cells when they were activated,whereas CD41+CD25- T cells showed strong expression of surface HLA-F when activated under identical conditions. These findings are discussed with regard to possible functions for HLA-F and its potential clinical use as a marker of an activated immune response. PMID:20865824

Lee, Ni; Ishitani, Akiko; Geraghty, Daniel E

2010-08-01

314

Blocking of monocyte-associated B7-H1 (CD274) enhances HCV-specific T cell immunity in chronic hepatitis C infection.  

PubMed

The establishment of a chronic hepatitis C (CHC) infection is associated with defective HCV-specific T cell responses. Recent studies suggest that negative T cell regulators such as programmed death 1 (PD-1) contribute to the impairment of virus-specific T cell functions in chronic viral infections. However, the implication of peripheral monocytes from CHC patients in the inhibition of HCV-specific T cell responses is only partially defined. In this study, we found that B7-H1, a ligand of PD-1, was significantly up-regulated on monocytes of CHC patients. Proliferation of T cells in response to anti-CD3 antibody was directly suppressed by B7-H1+CD14+ monocytes, and this suppression was reversed by addition of antagonistic B7-H1 mAb. Furthermore, blocking of monocyte-associated B7-H1 (moB7-H1) significantly enhanced the frequency of IFN-gamma-producing, HCV-specific CD4+ and CD8+ effector T cells and the production of Th1 cytokines, such as IL-2 but not Th2 cytokines, including IL-4 and IL-10. Upon B7-H1 blockade, production of perforin was also increased in CD8+ T cells stimulated with HCV peptides. Our findings suggest that moB7-H1 inhibits HCV-specific CD4+ and CD8+ T lymphocyte proliferation and suppresses Th1 cytokine production and perforin secretion. Blockade of the B7-H1 pathway thus represents an attractive approach in the treatment of chronic HCV infection. PMID:18086898

Jeong, Hye-Young; Lee, Youn-Jae; Seo, Su-Kil; Lee, Soo-Woong; Park, Sung-Jae; Lee, Jeong-Nyeo; Sohn, Hae-Sook; Yao, Sheng; Chen, Lieping; Choi, Inhak

2008-03-01

315

Monocyte trafficking to hepatic sites of bacterial infection is chemokine independent and directed by focal intercellular adhesion molecule-1 expression.  

PubMed

Recruitment of CCR2(+)Ly6C(high) monocytes to sites of infection is essential for efficient clearance of microbial pathogens. Although CCR2-mediated signals promote monocyte emigration from bone marrow, the contribution of CCR2 to later stages of monocyte recruitment remains unresolved. In this article, we show that CCR2 deficiency markedly worsens hepatic Listeria monocytogenes infection because Ly6C(high) monocytes are retained in the bone marrow. Intravenously transferred, CCR2-deficient Ly6C(high) monocytes traffic normally to hepatic foci of infection and contribute to bacterial clearance. Pertussis toxin treatment of adoptively transferred monocytes does not impair their intrahepatic trafficking, suggesting that chemokine signaling, once CCR2(+)Ly6C(high) monocytes emigrate from the bone marrow, is not required for monocyte localization to sites of bacterial infection in the liver. Expression of ICAM-1 is induced in close proximity to foci of bacterial infection in the liver, including on CD31(+) endothelial cells, and blockade of CD11b and CD44 diminishes monocyte localization to these hepatic foci. Our studies demonstrated that Ly6C(high) monocyte recruitment from the bloodstream to the L. monocytogenes-infected liver does not require chemokine receptor-mediated signals but instead is principally dependent on integrin- and extracellular matrix-mediated monocyte adhesion. PMID:20435926

Shi, Chao; Velázquez, Peter; Hohl, Tobias M; Leiner, Ingrid; Dustin, Michael L; Pamer, Eric G

2010-06-01

316

Different TNF? expression elicited by glucose in monocytes from type 2 diabetes mellitus patients  

Microsoft Academic Search

Increased plasma concentrations of tumor necrosis factor alpha (TNF?) system components appear in type 2 diabetes patients with poor glycemic control. We have analyzed the expression of TNF?, TNFR1 and TNFR2 when monocytes and lymphocytes isolated from a group of recent onset type 2 diabetic patients, with fasting glucose levels below 7.0mM and glycated haemoglobin (Hb1Ac) in the normal range,

M. R. Chacón; J. Vendrell; M. Miranda; V. Ceperuelo-Mallafré; A. Megía; C. Gutiérrrez; J. M. Fernández-Real; C. Richart; A. Garcia-Espańa

2007-01-01

317

The Envelope Glycoprotein of Human Immunodeficiency Virus Type 1 Stimulates Release of Neurotoxins from Monocytes  

Microsoft Academic Search

Mononuclear phagocytes infected with human immunodeficiency virus 1 (HIV-1) produce soluble factors that kill neurons in culture. To define the molecular events that lead to neuron killing, HIV-1 proteins were tested for the ability to trigger release of neurotoxins from human monocytes and lymphocytes. None of the recombinant-derived HIV-1 proteins examined (reverse transcriptase, protease, gag, nef, or gp120) were directly

Dana Giulian; Elaine Wendt; Ken Vaca; Christine A. Noonan

1993-01-01

318

Phenotyping of leukocytes and granulocyte and monocyte phagocytic activity in the peripheral blood and uterus of cows with endometritis.  

PubMed

This study was a comparative evaluation of selected immunological parameters in peripheral blood and uterine wash samples from cows with a normal postpartum period compared with cows with endometritis. We aimed to determine the usefulness of these parameters in monitoring the puerperium. In total, 40 cows were included in the study: 20 had endometritis (experimental group), and 20 did not have uterine inflammation (control group). Animals were chosen on the basis of cytological and bacteriological test results. The tests were conducted 5, 22, and 40 days postpartum. In both groups, flow cytometric analysis of the surface molecules CD4, CD8, CD21, CD25, and CD14 in the peripheral blood and uterine washings was performed. Granulocyte and monocyte phagocytic activity was determined using a commercial Phagotest kit that was adapted for flow cytometry. The percentage of phagocytic granulocytes and monocytes in both the peripheral blood and the uterine washings was significantly lower for cows in the experimental group compared with the control group (P < 0.01). A significant decrease (P < 0.01) in the percentage of CD4+, CD25+, CD14+, and CD4 + CD25(high) leukocyte subpopulations was also observed in the peripheral blood of cows with endometritis. A significant decrease (P < 0.01) in CD21+ lymphocytes and an increase in CD8+ lymphocytes was detected in uterine washings. The results of this work indicate that cell immunity dysfunction may be the main factor causing advanced inflammation of the uterus in endometritis. Knowledge of the immunological mechanisms observed in cows with endometritis might aid in choosing the correct immunomodulating agent-based adjuvant therapy. PMID:24857644

Brodzki, P; Kostro, K; Brodzki, A; Lisiecka, U; Kurek, L; Marczuk, J

2014-08-01

319

LILRA2 Selectively Modulates LPS-Mediated Cytokine Production and Inhibits Phagocytosis by Monocytes  

PubMed Central

The activating immunoglobulin-like receptor, subfamily A, member 2 (LILRA2) is primarily expressed on the surface of cells of the innate immunity including monocytes, macrophages, neutrophils, basophils and eosinophils but not on lymphocytes and NK cells. LILRA2 cross-linking on monocytes induces pro-inflammatory cytokines while inhibiting dendritic cell differentiation and antigen presentation. A similar activating receptor, LILRA4, has been shown to modulate functions of TLR7/9 in dendritic cells. These suggest a selective immune regulatory role for LILRAs during innate immune responses. However, whether LILRA2 has functions distinct from other receptors of the innate immunity including Toll-like receptor (TLR) 4 and Fc?RI remains unknown. Moreover, the effects of LILRA2 on TLR4 and Fc?RI-mediated monocyte functions are not elucidated. Here, we show activation of monocytes via LILRA2 cross-linking selectively increased GM-CSF production but failed to induce IL-12 and MCP-1 production that were strongly up-regulated by LPS, suggesting functions distinct from TLR4. Interestingly, LILRA2 cross-linking on monocytes induced similar amounts of IL-6, IL-8, G-CSF and MIP-1? but lower levels of TNF?, IL-1?, IL-10 and IFN? compared to those stimulated with LPS. Furthermore, cross-linking of LILRA2 on monocytes significantly decreased phagocytosis of IgG-coated micro-beads and serum opsonized Escherichia coli but had limited effect on phagocytosis of non-opsonized bacteria. Simultaneous co-stimulation of monocytes through LILRA2 and LPS or sequential activation of monocytes through LILRA2 followed by LPS led lower levels of TNF?, IL-1? and IL-12 production compared to LPS alone, but had additive effect on levels of IL-10 and IFN? but not on IL-6. Interestingly, LILRA2 cross-linking on monocytes caused significant inhibition of TLR4 mRNA and protein, suggesting LILRA2-mediated suppression of LPS responses might be partly via regulation of this receptor. Taken together, we provide evidence that LILRA2-mediated activation of monocytes is significantly different to LPS and that LILRA2 selectively modulates LPS-mediated monocyte activation and Fc?RI-dependent phagocytosis.

Lu, Hao K.; Mitchell, Ainslie; Endoh, Yasumi; Hampartzoumian, Taline; Huynh, Owen; Borges, Luis; Geczy, Carolyn; Bryant, Katherine; Tedla, Nicodemus

2012-01-01

320

The use of human T-lymphocyte clones to study T-cell function in allergic contact dermatitis to urushiol.  

PubMed

Allergic contact dermatitis to poison ivy (Toxicodendron radicans) is believed to be mediated by T lymphocytes specific for the hapten urushiol. Activated T lymphocytes may produce pathology by a variety of mechanisms including direct cytotoxicity, production of lymphokines, recruitment of non-specific effector cells, non-specific cytotoxicity, and possibly autologous DR reactivity. The regulation and pathogenesis of this condition was studied by cloning and characterizing urushiol-specific T cells from the peripheral blood of patients with poison ivy dermatitis. Multiple CD8+ (T8+) urushiol-specific clones were derived. All clones that proliferated in response to a crude extract of T. radicans also proliferated in response to purified urushiol. Thus, urushiol appears to be the single immunogenic component of T. radicans resin. Pentadecylcatechol (PDC), which differs from urushiol only in the lack of unsaturated bonds in its lipophilic tail, stimulated only one of seven clones tested. This suggests that the double bonds in the C15 lipophilic tail of urushiol are required for antigenicity. Several of the CD8+ urushiol-specific clone suppressed pokeweed mitogen-induced IgG production in the presence of urushiol. Suppression was triggered specifically by urushiol and required MHC compatibility both for the antigen-presenting cells and the responding B cells. These suppressor clones were isolated from convalescent blood and may represent a mechanism for the termination of an allergic contact dermatitis. PMID:1693644

Kalish, R S

1990-06-01

321

Analysis of monocyte chemoattractant protein 1-mediated lung injury using rat lung organ cultures.  

PubMed Central

Using a rat lung organ culture system, we analyzed the role of monocyte chemoattractant protein 1 (MCP 1) in leukocyte to lung adhesive interactions and monocyte-mediated lung injury. Quantitative leukocyte to lung adhesive interactions were examined using an adaptation of the Woodruff-Stamper frozen section binding assay. Pretreatment of organ cultures with recombinant human tumor necrosis factor (rhTNF alpha) resulted in a protein synthesis-dependent increase in the adhesiveness of lung tissue for peripheral blood monocytes. Adhesion of monocytes to lung tissue was not increased above baseline after 7 hours but increased more than twofold by 24 hours and persisted through 48 hours. Binding of monocyte to lung tissue was further increased when recombinant rat MCP 1 was added to monocyte suspensions immediately before being layered onto lung sections derived from either TNF alpha-treated or untreated organ cultures. Addition of antibody directed against rat CD11b/c resulted in a moderate reduction in monocyte binding. TNF or lipopolysaccharide-induced activation of mononuclear cells in the presence of [3H]leucine-labeled organ cultures resulted in lung injury as assessed by radioisotope release. Mononuclear cell-mediated organ culture injury could be partially inhibited with anti-rat MCP 1 antibody, anti-rat CD11b/c antibody, or antioxidants including catalase and deferoxamine. Anti-MCP 1 and anti-CD11b/c increased the absolute numbers of monocytes that could be retrieved from monocyte-lung co-cultures while catalase and deferoxamine did not. In vitro studies revealed that isolated rat peripheral blood monocytes produce O2- in response to MCP 1. These data provide a functional correlate for recent in vitro studies which suggest that MCP 1 may mediate leukocyte adhesive processes by up-regulating beta 2 integrin expression on monocytes. This study provides evidence that monocytes activated by MCP 1 can damage lung tissue through an oxidant-mediated mechanism. Monocyte chemoattractant protein 1 may participate in the pathogenesis of monocyte-mediated lung injury by modulating inflammatory cell adhesion as well as through monocyte activation. Images Figure 2

Warren, J. S.; Jones, M. L.; Flory, C. M.

1993-01-01

322

Angiotensin II Induces Monocyte Chemoattractant Protein1 Gene Expression in Rat Vascular Smooth Muscle Cells  

Microsoft Academic Search

Monocyte infiltration into the vessel wall, a key initial step in the process of atherosclerosis, is mediated in part by monocyte chemoattractant protein-1 (MCP-1). Hypertension, particularly in the presence of an activated renin-an- giotensin system, is a major risk factor for the development of atherosclerosis. To investigate a potential molecular basis for a link between hypertension and atherosclerosis, we studied

Xi-Lin Chen; Pradyumna E. Tummala; Matthew T. Olbrych; R. Wayne Alexander; Russell M. Medford

323

Phagocytosis-enhancing effect of lactoferrin on bovine peripheral blood monocytes in vitro and in vivo.  

PubMed

The effect of lactoferrin (LF) on in vitro and in vivo phagocytic ability of bovine blood monocytes was studied. It was demonstrated that bovine LF enhanced in vitro phagocytosis of bacteria and ovine erythrocyte-antibody complexes and increased intracellular killing of Staphylococcus albus. Monocytes of colostrum deprived calves, which were intravenously injected with LF, also exhibited elevated phagocytic properties. PMID:9071453

Szuster-Ciesielska, A; Kami?ska, T; Kandefer-Szersze?, M

1995-01-01

324

Why do cytotoxic T lymphocytes fail to eliminate hepatitis C virus? Lessons from studies using major histocompatibility complex class I peptide tetramers.  

PubMed Central

Hepatitis C virus (HCV) infection is a major public health problem, affecting an estimated 3% of the world's population, and over 10% in some countries. Infection in most cases becomes persistent, and can lead to hepatic inflammation, fibrosis and liver failure. The T lymphocyte reponse, in particular that mediated by cytotoxic T lymphocytes (CTLs), is likely to be involved in determining the outcome of infection, although its overall role is not clear. The use of major histocompatibility complex (MHC) class I peptide tetrameric complexes (tetramers) to study antiviral CTL responses has revolutionized our approach to the study of human infection. We have used a panel of MHC class I tetramers to analyse immune responses in HCV-infected individuals at various stages of disease. We find that the CTL response against HCV is vigorous in its early phases but dwindles over time both in terms of lymphocyte number and function. A number of potential explanations for this 'CTL failure' are discussed.

Lechner, F; Sullivan, J; Spiegel, H; Nixon, D F; Ferrari, B; Davis, A; Borkowsky, B; Pollack, H; Barnes, E; Dusheiko, G; Klenerman, P

2000-01-01

325

Plasma and lymphocyte Hsp72 responses to exercise in athletes with prior exertional heat illness.  

PubMed

We investigated the effect of exercise in the heat on both intracellular and extracellular Hsp72 in athletes with a prior history of exertional heat illness (EHI). Two groups of runners, one consisting of athletes who had a previous history of EHI, and a control group (CON) of similar age (29.7 ± 1.2 and 29.1 ± 2 years CON vs. EHI) and fitness [maximal oxygen consumption [Formula: see text] 65.7 ± 2 and 64.5 ± 3 ml kg(-1) min(-1) CON vs. EHI] were recruited. Seven subjects in each group ran on a treadmill for 1 h at 72 % [Formula: see text] in warm conditions (30 °C, 40 % RH) reaching rectal temperatures of ~39.3 (CON) and ~39.2 °C (EHI). Blood was collected every 10 min during exercise and plasma was analysed for extracellular Hsp72. Intracellular Hsp72 levels were measured in both monocytes and lymphocytes before and immediately after the 60-min run, and then after 1 h recovery at an ambient temperature of 24 °C. Plasma Hsp72 increased from 1.18 ± 0.14 and 0.86 ± 0.08 ng/ml (CON vs. EHI) at rest to 4.56 ± 0.63 and 4.04 ± 0.45 ng/ml (CON vs. EHI, respectively) at the end of exercise (p < 0.001), with no difference between groups. Lymphocyte Hsp72 was lower in the EHI group at 60 min of exercise (p < 0.05), while monocyte Hsp72 was not different between groups. The results of the present study suggest that the plasma Hsp72 response to exercise in athletes with a prior history of EHI remained similar to that of the CON group, while the lymphocyte Hsp72 response was reduced. PMID:24633453

Ruell, Patricia A; Simar, David; Périard, Julien D; Best, Stuart; Caillaud, Corinne; Thompson, Martin W

2014-06-01

326

In vitro binding and survival assays of Leishmania parasites to peripherical blood monocytes and monocyte-derived macrophages isolated from dogs naturally and experimentally infected with Leishmania (Leishmania) chagasi  

PubMed Central

Background There are a few works considering the characterization of canine monocyte-derived macrophages as well as a standardized procedure for isolation, culture, and infection of these cells with Leishmania. We have performed several modifications in order to improve the canine monocyte-derived macrophage cultures. In addition, we have done a comparative study between monocytes and monocyte-derived macrophages from dogs naturally and experimentally infected with L. chagasi. Results In the presence of exogenous serum, opsonized Leishmania promastigotes binds better to monocytes/macrophages than without serum. Otherwise, this binding occurs due to the strict correlation between the opsonized biologic particles with the third receptor of the complement (CR3-CD11b/CD18). In fact, our assays with CD11b confirmed the importance of this receptor for canine cells and the L. chagasi experimental system. Moreover, monocytes obtained from naturally infected dogs have shown a higher number of monocytes bounded to promastigotes. The experimental results regarding survival have shown that promastigote forms of opsonized L. chagasi were more infective, because we found higher numbers of promastigotes bound to the different cells. As a consequence, after forty-eight hours of binding, higher numbers of amastigotes appeared inside monocyte-macrophages. Conclusion These studies have given support to continue comparative studies involving canine monocytes, monocyte-derived macrophages and peritoneal macrophages. Since we have standardized the canine cell culture, we are looking forward to determining the phenotypic properties of these cells before and after L. chagasi infection using flow cytometry.

Sampaio, Weverton M; Moura, Eliane P; Arruda, Felipe CS; Ribeiro, Raul R; Alves, Cintia F; Melo, Ferdinan A; Fernandes, Ana Paula SM; Michalick, Marilene SM; Melo, Maria N; Tafuri, Washington L; Tafuri, Wagner L

2007-01-01

327

Involvement of ADAM9 in multinucleated giant cell formation of blood monocytes.  

PubMed

Monocytes-macrophages are converted to multinucleated giant cells by stimulation with various cytokines, and osteoclasts are the multinucleated giant cells derived from a monocyte-macrophage lineage. However, at present, the fusion peptides have not been clearly identified in monocytes-macrophages. The ADAM are a family of transmembrane glycoproteins that have a role in various biological functions. Interestingly, fertilin-alpha, ADAM9, and ADAM11 have potential fusion peptides. In this study, which ADAM was specifically expressed in monocytes stimulated with anti-CD98 antibody or RANKL and which factor(s) was functioning in monocytes as a fusion protein were investigated. ADAM1, 8, 10, 12, 15, 17, 20, and 21 mRNAs are expressed in blood monocytes incubated with control antibody, anti-FRP-1/CD98 antibody, or RANKL + M-CSF, while ADAM2, 7, 11, 13, 19, 23, 29, and 30 mRNAs could not be detected in these blood monocytes. Expression of ADAM9 and ADAM10 mRNAs are enhanced by either RANKL + M-CSF or anti-CD98 antibody. The expression of ADAM9 and ADAM10 is also induced in blood monocytes by anti-CD98 mAb. An anti-ADAM9 antibody enhances CD98-mediated cell aggregation, while it blocks CD98-mediated and RANKL-mediated multinucleated giant cell formation. A hydroxamate-based metalloprotease inhibitor, SI-27, which is found to suppress ADAM9 activity, suppresses multinucleated giant cell formation. New protein synthesis is necessary for the expression of ADAM9 mRNA and genistein suppresses induction of ADAM9 mRNA. This is the first report that ADAM9 is involved in monocyte fusion, such as CD98-mediated and RANKL-mediated cell fusion of blood monocytes. Furthermore, AMAM9 is one candidate for a fusion peptide in blood monocytes. PMID:11831872

Namba, K; Nishio, M; Mori, K; Miyamoto, N; Tsurudome, M; Ito, M; Kawano, M; Uchida, A; Ito, Y

2001-11-01

328

Periodontitis-activated monocytes/macrophages cause aortic inflammation.  

PubMed

A relationship between periodontal disease and atherosclerosis has been suggested by epidemiological studies. Ligature-induced experimental periodontitis is an adequate model for clinical periodontitis, which starts from plaque accumulation, followed by inflammation in the periodontal tissue. Here we have demonstrated using a ligature-induced periodontitis model that periodontitis activates monocytes/macrophages, which subsequently circulate in the blood and adhere to vascular endothelial cells without altering the serum TNF-? concentration. Adherent monocytes/macrophages induced NF-?B activation and VCAM-1 expression in the endothelium and increased the expression of the TNF-? signaling cascade in the aorta. Peripheral blood-derived mononuclear cells from rats with experimental periodontitis showed enhanced adhesion and increased NF-?B/VCAM-1 in cultured vascular endothelial cells. Our results suggest that periodontitis triggers the initial pathogenesis of atherosclerosis, inflammation of the vasculature, through activating monocytes/macrophages. PMID:24893991

Miyajima, Shin-Ichi; Naruse, Keiko; Kobayashi, Yasuko; Nakamura, Nobuhisa; Nishikawa, Toru; Adachi, Kei; Suzuki, Yuki; Kikuchi, Takeshi; Mitani, Akio; Mizutani, Makoto; Ohno, Norikazu; Noguchi, Toshihide; Matsubara, Tatsuaki

2014-01-01

329

Periodontitis-activated monocytes/macrophages cause aortic inflammation  

PubMed Central

A relationship between periodontal disease and atherosclerosis has been suggested by epidemiological studies. Ligature-induced experimental periodontitis is an adequate model for clinical periodontitis, which starts from plaque accumulation, followed by inflammation in the periodontal tissue. Here we have demonstrated using a ligature-induced periodontitis model that periodontitis activates monocytes/macrophages, which subsequently circulate in the blood and adhere to vascular endothelial cells without altering the serum TNF-? concentration. Adherent monocytes/macrophages induced NF-?B activation and VCAM-1 expression in the endothelium and increased the expression of the TNF-? signaling cascade in the aorta. Peripheral blood-derived mononuclear cells from rats with experimental periodontitis showed enhanced adhesion and increased NF-?B/VCAM-1 in cultured vascular endothelial cells. Our results suggest that periodontitis triggers the initial pathogenesis of atherosclerosis, inflammation of the vasculature, through activating monocytes/macrophages.

Miyajima, Shin-ichi; Naruse, Keiko; Kobayashi, Yasuko; Nakamura, Nobuhisa; Nishikawa, Toru; Adachi, Kei; Suzuki, Yuki; Kikuchi, Takeshi; Mitani, Akio; Mizutani, Makoto; Ohno, Norikazu; Noguchi, Toshihide; Matsubara, Tatsuaki

2014-01-01

330

A new role for monocytes in modulating myometrial inflammation during human labor.  

PubMed

Here we fully characterize the cytokine profile of laboring human myometrium using Luminex analysis of 48 cytokine proteins, and stereologically quantified infiltration of monocytes and neutrophils into the myometrium. We hypothesized that monocytes can regulate their accumulation in the myometrium by disruption of proinflammatory cytokines to prevent an uncontrolled inflammatory response after labor onset. We isolated primary human myometrial cells (HMCs) from term, nonlaboring myometrial biopsies. Confluent HMCs were cocultured directly with human monocytic (THP-1) or lymphocytic (U937) cells, and with the same cells spatially separated by a membrane insert. After 72 h, HMCs and THP-1 were harvested separately, and RNA was extracted and analyzed by quantitative PCR. Coculture supernatants were collected and analyzed by Luminex assay and ELISA. We found that the laboring human myometrium produces significantly higher amounts of interleukin (IL) 6, IL9, IL18, IL1RA, CCL2, CCL7, CXCL8, CSF3, and tumor necrosis factor alpha, which coincides with the influx of immune cells. The direct contact or presence of THP-1 monocytes (but not U937 cells) significantly decreased CCL2 protein levels and increased IL1RA protein levels secreted by HMCs. This time-dependent decrease of CCL2 was greater with increasing number of monocytes being in direct contact with HMCs. We suggest a novel mechanism by which monocytes are first recruited to the myometrium by multiple cytokines and contribute to the physiologic inflammation of labor. After completing transmigration, activated monocytes disrupt locally established CCL2 gradients (possible by CCR2-mediated consumption) to limit their accumulation in the uterus. This mechanism may serve as a negative feedback loop to control the local inflammation and promote a return to homeostasis. PMID:24829032

Srikhajon, Khetsopon; Shynlova, Oksana; Preechapornprasert, Anyarin; Chanrachakul, Boonsri; Lye, Stephen

2014-07-01

331

A phase II study of sequential combination chemotherapy with cyclophosphamide, prednisone, and 2-chlorodeoxyadenosine in previously untreated patients with chronic lymphocytic leukemia  

Microsoft Academic Search

In an earlier study of previously untreated patients with chronic lymphocytic leukemia (CLL), we used a concomitant combination of chlorambucil and 2-chlorodeoxyadenosine and reported overall (OR) and complete (CR) remission rates of 80% and 20%, respectively. After a median follow-up of 5 years, more than 80% of the responders have had a relapse. In the current phase II study of

A Tefferi; C-Y Li; CB Reeder; SM Geyer; C Allmer; R Levitt; JC Michalak; F Addo; JE Krook; TE Witzig; PL Schaefer; JA Mailliard; A Tefferi

2001-01-01

332

Distinct Responses of Human Monocyte Subsets to Aspergillus fumigatus Conidia1  

PubMed Central

Aspergillus fumigatus is an environmental fungus that causes life-threatening infections in neutropenic patients. In the absence of intact innate immunity, inhaled A. fumigatus spores (conidia) germinate in the lung, forming hyphae that invade blood vessels and disseminate to other tissues. Although macrophages and neutrophils are postulated to provide defense against invasive fungal infection, animal models and human studies suggest that circulating monocytes also contribute to antifungal immunity. Although human monocyte subsets, defined as either CD14+CD16? or CD14+ CD16+, have been extensively characterized, their respective roles during fungal infection remain undefined. We isolated CD14+CD16? and CD14+CD16+ monocytes from healthy allogeneic hematopoietic stem cell transplantation donors and compared their ability to phagocytose and inhibit A. fumigatus conidia. Both monocyte subsets efficiently phagocytose conidia, but only CD14+CD16? monocytes inhibit conidial germination yet secrete little TNF. In contrast CD14+CD16+ do not inhibit conidial germination and secrete large amounts of TNF. Although CD14+CD16? and CD14+CD16+ monocytes differ in their response to dormant conidia, responses are similar if conidia are already germinated at the time of monocyte uptake. Our study demonstrates that functional CD14+CD16? and CD14+CD16+ monocytes can be isolated from allogeneic hematopoietic stem cell transplantation donors and that these subsets differ in their response to A. fumigatus conidia.

Serbina, Natalya V.; Cherny, Mathew; Shi, Chao; Bleau, Sharon A.; Collins, Nancy H.; Young, James W.; Pamer, Eric G.

2009-01-01

333

Monocyte Subset Dynamics in Human Atherosclerosis Can Be Profiled with Magnetic Nano-Sensors  

PubMed Central

Monocytes are circulating macrophage and dendritic cell precursors that populate healthy and diseased tissue. In humans, monocytes consist of at least two subsets whose proportions in the blood fluctuate in response to coronary artery disease, sepsis, and viral infection. Animal studies have shown that specific shifts in the monocyte subset repertoire either exacerbate or attenuate disease, suggesting a role for monocyte subsets as biomarkers and therapeutic targets. Assays are therefore needed that can selectively and rapidly enumerate monocytes and their subsets. This study shows that two major human monocyte subsets express similar levels of the receptor for macrophage colony stimulating factor (MCSFR) but differ in their phagocytic capacity. We exploit these properties and custom-engineer magnetic nanoparticles for ex vivo sensing of monocytes and their subsets. We present a two-dimensional enumerative mathematical model that simultaneously reports number and proportion of monocyte subsets in a small volume of human blood. Using a recently described diagnostic magnetic resonance (DMR) chip with 1 µl sample size and high throughput capabilities, we then show that application of the model accurately quantifies subset fluctuations that occur in patients with atherosclerosis.

Wildgruber, Moritz; Lee, Hakho; Chudnovskiy, Aleksey; Yoon, Tae-Jong; Etzrodt, Martin; Pittet, Mikael J.; Nahrendorf, Matthias; Croce, Kevin; Libby, Peter; Weissleder, Ralph; Swirski, Filip K.

2009-01-01

334

Increased angiotensin-converting enzyme in peripheral blood monocytes from patients with sarcoidosis.  

PubMed Central

Angiotensin-converting enzyme (ACE) activity was measured in isolated peripheral blood monocytes and culture medium from 28 patients with sarcoidosis and compared with values obtained from monocytes of 25 normal control subjects. ACE activity was determined by radioimmunoassay of angiotensin II produced from angiotensin I. While there was no measurable ACE activity in monocytes or culture medium from normal controls under the conditions of our study, monocytes from patients with sarcoidosis all showed activity both in cells and culture medium. The mean ACE activity of monocytes from patients with sarcoidosis was 2.0 pg angiotensin II formed/min per 10(5) cells, and that released into medium over a 24-h interval was 30.4 pg angiotensin II/min per 10(5) cells. The monocyte ACE from patients with sarcoidosis was activated by chloride ions and inhibited by EDTA, captopril, and rabbit antiserum to purified human plasma ACE, indicating that enzymatic activity was effected specifically by ACE. Thus, our studies show a significant elevation and release of ACE by peripheral blood monocytes of patients with sarcoidosis under conditions where monocytes of normal control subjects do not demonstrate ACE activity.

Okabe, T; Yamagata, K; Fujisawa, M; Watanabe, J; Takaku, F; Lanzillo, J J; Fanburg, B L

1985-01-01

335

HIV-1 Induces Telomerase Activity in Monocyte-Derived Macrophages, Possibly Safeguarding One of Its Reservoirs  

PubMed Central

Monocyte-derived macrophages (MDM) are widely distributed in all tissues and organs, including the central nervous system, where they represent the main part of HIV-infected cells. In contrast to activated CD4+ T lymphocytes, MDM are resistant to cytopathic effects and survive HIV infection for a long period of time. The molecular mechanisms of how HIV is able to persist in macrophages are not fully elucidated yet. In this context, we have studied the effect of in vitro HIV-1 infection on telomerase activity (TA), telomere length, and DNA damage. Infection resulted in a significant induction of TA. This increase was directly proportional to the efficacy of HIV infection and was found in both nuclear and cytoplasmic extracts, while neither UV light-inactivated HIV nor exogenous addition of the viral protein Tat or gp120 affected TA. Furthermore, TA was not modified during monocyte-macrophage differentiation, MDM activation, or infection with vaccinia virus. HIV infection did not affect telomere length. However, HIV-infected MDM showed less DNA damage after oxidative stress than noninfected MDM, and this resistance was also increased by overexpressing telomerase alone. Taken together, our results suggest that HIV induces TA in MDM and that this induction might contribute to cellular protection against oxidative stress, which could be considered a viral strategy to make macrophages better suited as longer-lived, more resistant viral reservoirs. In the light of the clinical development of telomerase inhibitors as anticancer therapeutics, inhibition of TA in HIV-infected macrophages might also represent a novel therapeutic target against viral reservoirs.

Reynoso, Rita; Wieser, Matthias; Ojeda, Diego; Bonisch, Maximilian; Kuhnel, Harald; Bolcic, Federico; Quendler, Heribert; Grillari, Johannes

2012-01-01

336

HIV-1 induces telomerase activity in monocyte-derived macrophages, possibly safeguarding one of its reservoirs.  

PubMed

Monocyte-derived macrophages (MDM) are widely distributed in all tissues and organs, including the central nervous system, where they represent the main part of HIV-infected cells. In contrast to activated CD4(+) T lymphocytes, MDM are resistant to cytopathic effects and survive HIV infection for a long period of time. The molecular mechanisms of how HIV is able to persist in macrophages are not fully elucidated yet. In this context, we have studied the effect of in vitro HIV-1 infection on telomerase activity (TA), telomere length, and DNA damage. Infection resulted in a significant induction of TA. This increase was directly proportional to the efficacy of HIV infection and was found in both nuclear and cytoplasmic extracts, while neither UV light-inactivated HIV nor exogenous addition of the viral protein Tat or gp120 affected TA. Furthermore, TA was not modified during monocyte-macrophage differentiation, MDM activation, or infection with vaccinia virus. HIV infection did not affect telomere length. However, HIV-infected MDM showed less DNA damage after oxidative stress than noninfected MDM, and this resistance was also increased by overexpressing telomerase alone. Taken together, our results suggest that HIV induces TA in MDM and that this induction might contribute to cellular protection against oxidative stress, which could be considered a viral strategy to make macrophages better suited as longer-lived, more resistant viral reservoirs. In the light of the clinical development of telomerase inhibitors as anticancer therapeutics, inhibition of TA in HIV-infected macrophages might also represent a novel therapeutic target against viral reservoirs. PMID:22787205

Reynoso, Rita; Wieser, Matthias; Ojeda, Diego; Bönisch, Maximilian; Kühnel, Harald; Bolcic, Federico; Quendler, Heribert; Grillari, Johannes; Grillari-Voglauer, Regina; Quarleri, Jorge

2012-10-01

337

Cytokine Pattern of T Lymphocytes in Acute Schistosomiasis mansoni Patients following Treated Praziquantel Therapy  

PubMed Central

Acute schistosomiasis is associated with a primary exposure and is more commonly seen in nonimmune individuals traveling through endemic regions. In this study, we have focused on the cytokine profile of T lymphocytes evaluated in circulating leukocytes of acute Schistosomiasis mansoni-infected patients (ACT group) before and after praziquantel treatment (ACT-TR group). Our data demonstrated increased values of total leukocytes, eosinophils, and monocytes in both groups. Interestingly, we have observed that patients treated with praziquantel showed increased values of lymphocytes as compared with noninfected group (NI) or ACT groups. Furthermore, a decrease of neutrophils in ACT-TR was observed when compared to ACT group. Analyses of short-term in vitro whole blood stimulation demonstrated that, regardless of the presence of soluble Schistosoma mansoni eggs antigen (SEA), increased synthesis of IFN-? and IL-4 by T-cells was observed in the ACT group. Analyses of cytokine profile in CD8 T cells demonstrated higher percentage of IFN-? and IL-4 cells in both ACT and ACT-TR groups apart from increased percentage of IL-10 cells only in the ACT group. This study is the first one to point out the relevance of CD8 T lymphocytes in the immune response induced during the acute phase of schistosomiasis.

Silveira-Lemos, Denise; Fernandes Costa-Silva, Matheus; Cardoso de Oliveira Silveira, Amanda; Azevedo Batista, Mauricio; Alves Oliveira-Fraga, Lucia; Soares Silveira, Alda Maria; Barbosa Alvarez, Maria Carolina; Martins-Filho, Olindo Assis; Gazzinelli, Giovanni; Correa-Oliveira, Rodrigo; Teixeira-Carvalho, Andrea

2013-01-01

338

Novel 17-kilodalton Leishmania antigen revealed by immunochemical studies of a purified glycoprotein fraction recognized by murine T lymphocytes.  

PubMed Central

Recently, a glycoprotein fraction, designated gp10/20, purified from Leishmania mexicana amazonensis was shown to induce a cellular immune response mediated by murine L3T4+ T lymphocytes. This fact led us to pursue further the characterization of this fraction. The present study demonstrated that gp10/20 is a degradation product of a 17-kilodalton antigen present in promastigotes and amastigotes of L. mexicana amazonensis. This antigen was easily detected in promastigotes of L. mexicana mexicana, L. donovani, L. chagasi, L. major, and L. tropica. However, culture forms of L. braziliensis complex expressed either low amounts of the 17-kilodalton antigen or an antigenically unrelated antigen. The recognition of gp10/20 by several serum samples of patients with kala-azar was also shown. Images

Rodrigues, M M; Xavier, M T; Mendonca-Previato, L; Barcinski, M A

1988-01-01

339

Hairy Cell Leukemia (‘Leukemic Reticuloendotheliosis’), Reticulosarcoma, and Monocytic Leukemia  

Microsoft Academic Search

Cytochemical and electron-microscopic studies have been carried out on leukemic monocytes and ‘hairy cells’ (HC), ‘reticulosarcoma’ (RS) cells and cells of cases of ‘reticulosis’ and ‘reticulosarcoma cell leukemia’. Additional investigations included quantitative determinations of the urinary lysozyme excretion, skin window studies, testing of the phagocytosis of ferritin by HC, and labelling of the Fc receptors on HC at the ultrastructural

F. Schmalzl; D. Huhn; H. Asamer; H. Braunsteiner

1975-01-01

340

Lymphocyte count was significantly associated with hyper-LDL cholesterolemia independently of high-sensitivity C-reactive protein in apparently healthy Japanese  

Microsoft Academic Search

The aim of this study was to investigate the association between leukocyte subtype counts and hyper-LDL cholesterolemia, hypertriglyceridemia,\\u000a and hypo-HDL cholesterolemia. Logistic regressions using hyper-LDL cholesterolemia, hypertriglyceridemia, and hypo-HDL cholesterolemia\\u000a as a dependent variable and total leukocyte, basophil, eosinophil, neutrophil, lymphocyte, and monocyte counts as an independent\\u000a variable were calculated adjusting for age, body mass index (BMI), high-sensitivity C-reactive protein

Eiji Oda; Ryu Kawai; Yoshifusa Aizawa

341

Distinct functions of chemokine receptor axes in the atherogenic mobilization and recruitment of classical monocytes  

PubMed Central

We used a novel approach of cytostatically induced leucocyte depletion and subsequent reconstitution with leucocytes deprived of classical (inflammatory/Gr1hi) or non-classical (resident/Gr1lo) monocytes to dissect their differential role in atheroprogression under high-fat diet (HFD). Apolipoprotein E-deficient (Apoe?/?) mice lacking classical but not non-classical monocytes displayed reduced lesion size and macrophage and apoptotic cell content. Conversely, HFD induced a selective expansion of classical monocytes in blood and bone marrow. Increased CXCL1 levels accompanied by higher expression of its receptor CXCR2 on classical monocytes and inhibition of monocytosis by CXCL1-neutralization indicated a preferential role for the CXCL1/CXCR2 axis in mobilizing classical monocytes during hypercholesterolemia. Studies correlating circulating and lesional classical monocytes in gene-deficient Apoe?/? mice, adoptive transfer of gene-deficient cells and pharmacological modulation during intravital microscopy of the carotid artery revealed a crucial function of CCR1 and CCR5 but not CCR2 or CX3CR1 in classical monocyte recruitment to atherosclerotic vessels. Collectively, these data establish the impact of classical monocytes on atheroprogression, identify a sequential role of CXCL1 in their mobilization and CCR1/CCR5 in their recruitment.

Soehnlein, Oliver; Drechsler, Maik; Doring, Yvonne; Lievens, Dirk; Hartwig, Helene; Kemmerich, Klaus; Ortega-Gomez, Almudena; Mandl, Manuela; Vijayan, Santosh; Projahn, Delia; Garlichs, Christoph D; Koenen, Rory R; Hristov, Mihail; Lutgens, Esther; Zernecke, Alma; Weber, Christian

2013-01-01

342

Blood monocytes in rheumatoid arthritis are highly adherent to cultured endothelium.  

PubMed

Monocytes from 17 patients with rheumatoid arthritis (RA) were more adherent than monocytes from 17 control patients to monolayers of pig aortic endothelium irrespective of whether sera was included (median 27-34% increase; p = 0.002) or omitted (median 27% increase; p = 0.022) from the culture media. When human umbilical vein endothelial cells were used as the adherence substrate, rheumatoid monocytes from an additional 21 patients demonstrated a median 31% (p = 0.004) and 20% increase (p = 0.004) in adhesion when compared with monocytes from 21 normal healthy subjects in the absence and presence of autologous sera, respectively. Activation of control monocytes with muramyl dipeptide or treatment with RA sera increased their attachment to endothelium (mean 34 +/- 14% increase; p < 0.001). The expression of the adhesion molecules CD11b (p < 0.005), CD18 (p < 0.005), CD62L (p = 0.01) was enhanced on rheumatoid monocytes, but antibody-blocking studies suggested that CD18 and CD62L were not responsible for the augmented binding of the rheumatoid cells. A subpopulation of rheumatoid monocytes possessed a very low net negative surface charge, a property that favours binding to vessel walls. We propose that many rheumatoid monocytes are predisposed for sheer-resistant adhesion to vascular endothelium. PMID:7580285

Mazure, G; Fernandes, T; McCarthy, D A; Macey, M; Perry, J D; Taub, N A; Dumonde, D C; Brown, K A

1995-11-01

343

Ouabain Affects the Expression of Activation Markers, Cytokine Production, and Endocytosis of Human Monocytes  

PubMed Central

Ouabain is a steroid capable of binding to and inhibiting Na+,-K+-ATPase. Studies have demonstrated some actions of ouabain on immune cells, which indicated both pro- and anti-inflammatory properties of this molecule. Nevertheless, its effects on human monocytes are still poorly understood. Thus, the present work investigated effects of ouabain in the activation and function of human adherent monocytes. Our results show that there is an increase in intracellular calcium levels already 5 minutes following monocyte treatment with 10?7?M of ouabain. Furthermore, monocytes expressed increased amounts of surface activation markers such as CD69, HLA-DR, CD86, and CD80 and also presented an augmented endocytic activity of dextran-FITC particles after 24 hours of culture in the presence of ouabain. However, monocytes treated with ouabain did not have an increased stimulatory capacity in allogeneic mixed leukocyte reaction. Ouabain-treated monocytes produced higher levels of IL-1? and TNF-? as reported before. A novel observation was the fact that ouabain induced IL-10 and VEGF as well. Collectively, these results suggest that ouabain impacts monocyte activation and modulates monocyte functions, implying that this steroid could act as an immunomodulator of these cells.

Teixeira, Mariana Pires; Rumjanek, Vivian Mary

2014-01-01

344

Ouabain affects the expression of activation markers, cytokine production, and endocytosis of human monocytes.  

PubMed

Ouabain is a steroid capable of binding to and inhibiting Na(+),-K(+)-ATPase. Studies have demonstrated some actions of ouabain on immune cells, which indicated both pro- and anti-inflammatory properties of this molecule. Nevertheless, its effects on human monocytes are still poorly understood. Thus, the present work investigated effects of ouabain in the activation and function of human adherent monocytes. Our results show that there is an increase in intracellular calcium levels already 5 minutes following monocyte treatment with 10(-7)?M of ouabain. Furthermore, monocytes expressed increased amounts of surface activation markers such as CD69, HLA-DR, CD86, and CD80 and also presented an augmented endocytic activity of dextran-FITC particles after 24 hours of culture in the presence of ouabain. However, monocytes treated with ouabain did not have an increased stimulatory capacity in allogeneic mixed leukocyte reaction. Ouabain-treated monocytes produced higher levels of IL-1 ? and TNF- ? as reported before. A novel observation was the fact that ouabain induced IL-10 and VEGF as well. Collectively, these results suggest that ouabain impacts monocyte activation and modulates monocyte functions, implying that this steroid could act as an immunomodulator of these cells. PMID:24904197

Teixeira, Mariana Pires; Rumjanek, Vivian Mary

2014-01-01

345

Monocyte ADAM17 promotes diapedesis during transendothelial migration: Identification of steps and substrates targeted by metalloproteinases  

PubMed Central

Despite expanded definition of the leukocyte adhesion cascade and mechanisms underlying individual steps, very little is known about regulatory mechanisms controlling sequential shifts between steps. We tested the hypothesis that metalloproteinases provide a mechanism to rapidly transition monocytes between different steps. Our study identifies diapedesis as a step targeted by metalloproteinase activity. Time-lapse video microscopy shows that the presence of a metalloproteinase inhibitor results in a doubling of the time required for human monocytes to complete diapedesis on unactivated or inflamed human endothelium, under both static and physiological-flow conditions. Thus, diapedesis is promoted by metalloproteinase activity. In contrast, neither adhesion of monocytes nor their locomotion over the endothelium is altered by metalloproteinase inhibition. We further demonstrate that metalloproteinase inhibition significantly elevates monocyte cell-surface levels of integrins CD11b/CD18 (Mac-1) specifically during transendothelial migration. Interestingly, such alterations are not detected for other endothelial- and monocyte-adhesion molecules that are presumed metalloproteinase substrates. Two major transmembrane metalloproteinases, ADAM17 and ADAM10, are identified as enzymes that control constitutive cleavage of Mac-1. We further establish that knockdown of monocyte ADAM17, but not endothelial ADAM10 or ADAM17, or monocyte ADAM10, reproduces the diapedesis delay observed with metalloproteinase inhibition. Therefore, we conclude that monocyte ADAM17 facilitates the completion of transendothelial migration by accelerating the rate of diapedesis. We propose that the progression of diapedesis may be regulated by spatial and temporal cleavage of Mac-1, which is triggered upon interaction with endothelium.

Tsubota, Yoshiaki; Frey, Jeremy M.; Tai, Phillip W.L.; Welikson, Robert E.; Raines, Elaine W.

2013-01-01

346

The detection of monocytes in human glomerulonephritis  

Microsoft Academic Search

The detection of monocytes in human glomerulonephritis. Renal biosy specimens from 343 patients with primary or secondary glomerulonephritis (GN) were examined for monocytes by the non-specific esterase reaction. Large numbers of monocytes per glomerulus (M\\/G) were found in essential cryoglobulinemia GN (29 pts, M\\/G 30.6 ± 22.4), in acute post-infectious GN (27 pts, M\\/G 9.1 ± 8.3), in rapidly progressive

Franco Ferrario; Aldo Castiglione; Guiliano Colasanti; Giovanni Barbiano di Belgioioso; Silvio Bertoli; Giuseppe D'Amico; Stefania Nava

1985-01-01

347

Suppression of lymphocyte proliferation by parainfluenza virus type 3-infected bovine alveolar macrophages.  

PubMed Central

Lymphocytes stimulated with concanavalin A (Con A) or antigen in the presence of bovine parainfluenza virus type 3 (PIV-3) infected bovine alveolar macrophages (BAM) or monocytes, had depressed [3H]thymidine incorporation. This failure of lymphocytes to incorporate radiolabel required live virus, was time dependent and was most pronounced when BAM were infected for 48 hr prior to the addition of lymphocytes. The rate of infection of alveolar macrophages and the release of infectious virus into culture supernatants paralleled suppression of lymphocyte mitogenesis by PIV-3. However, the peak titre of exogenous, live or inactivated virus was not suppressive when added to lymphocyte macrophage cultures just prior to Con A stimulation. Neither the loss of viable alveolar macrophages nor a shift in antigen or mitogen dose response in virally infected cultures could account for the deficit in [3H]thymidine incorporation by lymphocytes. Despite the presence of lymphocyte-associated virus antigen detected by direct immunofluorescence, no increase in PIV-3 titre above baseline was seen from infected lymphocytes, irrespective of mitogen stimulation. Likewise, lymphocytes did not contribute to the extracellular virus pool in lymphocyte-macrophage cultures as the increases in viral titre above basal levels in supernatants were equal to levels released by macrophages alone. The expression of viral antigen on lymphocytes stimulated in the presence of PIV-3-infected BAM suggests a non-productive or abortive infection of lymphocytes mediated through contact with infected macrophages. Images Figure 6 Figure 7 Figure 8

Basaraba, R J; Brown, P R; Laegreid, W W; Silflow, R M; Evermann, J F; Leid, R W

1993-01-01

348

Differential Responses Between Monocytes and Monocyte-Derived Macrophages for Lipopolysaccharide Stimulation of Calves  

Microsoft Academic Search

In this experiment Toll-like receptor expression pattern in monocytes and monocyte-derived macrophages by lipopolysaccharide (LPS) stimulation was examined. Jugular venous blood was collected from four Japanese calves, and the peripheral blood mononuclear cells (PBMCs) were isolated. The cells were directly used for collecting monocytes by magnetic cell sorting or cultured for 7 days to collect monocyte-derived macrophages in Repcell. Then

Yijie Guo; Guoqi Zhao; Sachi Tanaka; Takahiro Yamaguchi

2009-01-01

349

Maternal molecular features and gene profiling of monocytes during first trimester pregnancy.  

PubMed

We examined the molecular characteristics of monocytes of pregnant and non-pregnant women to investigate the molecular effects that are associated with immunoregulation at the maternal-fetal interface. We analyzed molecular features and target genes in monocytes of pregnant women using flow cytometry, real-time PCR and oligonucleotide microarray technology. CD14(high) monocytes and several immune gene members including CD200, CD200R, IDO, IFI27, IL-10 and G0S2 were found to be differentially expressed in monocytes throughout pregnancy. In addition, transcripts within components of the signaling cascade of immune cells (HLA-DRB4, HBEGF, IL-8, CD3D, CCL5), and of several transcription factors (SOCS1, CXCL10, ID1, ID2) were altered in the monocytes of pregnant women. Further studies will be needed to elucidate the biological significance of our observation. PMID:23958292

Koldehoff, Michael; Cierna, Barbara; Steckel, Nina K; Beelen, Dietrich W; Elmaagacli, Ahmet H

2013-09-01

350

Granulocyte, monocyte and blast immunophenotype abnormalities in acute myeloid leukemia with myelodysplasia-related changes.  

PubMed

Little literature exists regarding granulocyte and monocyte immunophenotype abnormalities in Acute Myeloid Leukemia (AML). We hypothesized that granulocyte and monocyte immunophenotype abnormalities are common in AML, and especially in AML with myelodysplasia-related changes (AMLMRC). Bone marrow or peripheral blood specimens from 48 cases of AML and 22 cases of control specimens were analyzed by flow cytometric immunophenotyping. Granulocyte, monocyte, and blast immunophenotype abnormalities were compared between cases of AML versus controls and AMLMRC versus AML without myelodysplasia. The results revealed that granulocyte, monocyte, and blast abnormalities were more common in AMLMRC than in AML without myelodysplasia or control cases. The difference reached statistical significance for abnormalities of granulocytes and abnormalities in all cells of interest. From the numerous individual abnormalities, only CD25 expression in blasts was significantly more prevalent in AMLMRC in this study. We conclude that detection of granulocyte, monocyte, and blast immunophenotype abnormalities can contribute to the diagnosis of AMLMRC. PMID:24695467

Ayar, Sonali P; Ravula, Sreelakshmi; Polski, Jacek M

2014-01-01

351

Synopsis and synthesis of candidate-gene association studies in chronic lymphocytic leukemia: the CUMAGAS-CLL information system.  

PubMed

A comprehensive and systematic assessment of the current status of candidate-gene association studies for chronic lymphocytic leukemia (CLL) was conducted. Data from 989 candidate-gene association studies (1992-2009) involving 905 distinct genetic variants were analyzed and cataloged in CUMAGAS-CLL, a Web-based information system which allows the retrieval and synthesis of data from candidate-gene association studies on CLL (http://biomath.med.uth.gr). Nine genetic variants (BAX (rs4645878), GSTM1 (null/present), GSTT1 (null/present), IL10 (rs1800896), LTA (rs909253), MTHFR (rs1801131), MTHFR (rs1801133), P2RX7 (rs3751143), and TNF (rs1800629)) were investigated in 4 or more studies, and their results were meta-analyzed. In individual studies, 147 variants showed a significant association with CLL risk under any genetic model. For 53 variants, the association was significant at P < 0.01 with an increased risk greater than 40%. Only 0.3% of studies had statistical power greater than 80%. In meta-analyses, none of the variants showed significant results, and heterogeneity ranged from none to high. Large and rigorous genetic studies (candidate-gene association studies and genome-wide association studies) designed to investigate epistatic and gene-environment interactions may produce more conclusive evidence about the genetic etiology of CLL. CUMAGAS-CLL would be a useful tool for current genomic epidemiology research in the field of CLL. PMID:19700502

Zintzaras, Elias; Kitsios, George D

2009-09-15

352

Cryopreservation of human monocytes for pharmacopeial monocyte activation test.  

PubMed

EU Directive 2010/63/EU regarding the protection of experimental animals came into force in November 2010 with an obligation for EU member states to incorporate its requirements into their respective national legislations by 1st of January 2013. The directive stipulates the application of in vitro methods to replace animal experiments whenever such an in vitro method exits and is recognized by EU legislation. The monocyte activation test (MAT) for the detection and quantification of pyrogenic contamination in medicines is recognized by the European Directorate for the Quality of Medicines & Health Care (EDQM) and was published in the European Pharmacopeia (Pharm. Eur.) in April 2010. The methodology described here facilitates the use of the MAT by making monocytes available, in the form of cryopreserved human peripheral blood mononuclear cells (PBMCs). We have developed and qualified a procedure to prepare functional monocytes in the form of PBMCs from the leukocyte filters that are used for the separation of blood in blood donation centers. Once used, these filters are normally treated as biological waste. Here we describe the procedures that are critical for the successful cryopreservation of PBMCs, demonstrate protection of PBMC functionality using various ligands for the toll-like receptors (TLRs) that mediate pyrogenic responses, report validation of the methodology for linearity, precision and robustness and show examples of the practical application of cryopreserved in MATs with samples of drugs and vaccines. Another application of cryopreserved PBMCs, only mentioned here, is to serve as an alternative to freshly isolated PBMCs in tests for unwanted intrinsic pro-inflammatory activities of new biological therapeutics. Such tests use PBMCs or PBMCs over a layer of endothelial cells to detect (unwanted) cytokine release, PBMCs being more suited to this purpose than tests using whole blood. PMID:24456627

Koryakina, Anna; Frey, Esther; Bruegger, Peter

2014-03-01

353

Magnesium contents of leukemic lymphocytes.  

PubMed

In this study, magnesium concentrations were measured in lymphocytes from patients with acute myeloblastic leukemia (AML), chronic megalositer leukemia (KML) and acute lymphoblastic leukemia (ALL) before and after chemotherapy management, and results were compared with those of control subjects. Magnesium concentrations were higher in the patient groups compared with control values. However, no meaningful differences were found among magnesium concentrations of the patient groups themselves. Similarly, no statistically meaningful differences were found between lymphocyte magnesium concentrations before and after chemotherapy management in the patient groups. In the inter-correlation analysis, we observed no correlations between pre- and post-magnesium concentrations in patients' lymphocytes. It has been suggested that magnesium concentrations of leukemic lymphocytes might increase due to the high ATP requirement of the leukemic cells since magnesium is known to play an important part as a cofactor in most of the energy-producing reactions. PMID:7812116

Canbolat, O; Kavutcu, M; Durak, I

1994-10-01

354

Monocyte-derived dendritic cells in innate and adaptive immunity  

Microsoft Academic Search

Monocytes have been classically considered essential elements in relation with innate immune responses against pathogens, and inflammatory processes caused by external aggressions, infection and autoimmune disease. However, although their potential to differentiate into dendritic cells (DCs) was discovered 14 years ago, their functional relevance with regard to adaptive immune responses has only been uncovered very recently. Studies performed over the

Beatriz León; Carlos Ardavín

2008-01-01

355

Carboxylesterase 1 (Ces1): from monocyte marker to major player  

Microsoft Academic Search

There are few, if any, enzymes that have been studied by, and have importance in, so many and varied disciplines as has monocyte esterase\\/Ces 1. In this review its involvement in the fields of histochemistry, haematology, toxicology, pharmacology, therapeutics, and tumour cell killing, immune surveillance and malignant disease, is briefly described.

Geraldine M Markey

2010-01-01

356

CD2 Identifies a Monocyte Subpopulation with IgE Dependent, High Level Expression of Fc?RI  

PubMed Central

Background Fc?RI expression by monocytes can affect monocyte function via multiple mechanisms, thereby potentially influencing the generation of allergic inflammation. Previous studies on the in vivo regulation of monocyte Fc?RI expression by ambient IgE have yielded conflicting results. Objective We hypothesized that monocyte Fc?RI expression is limited to a specific monocyte subset and that within that subset Fc?RI surface expression is correlated to serum IgE. Methods Study 1: Blood was obtained from nonallergic subjects (n = 14) and subjects with allergic asthma (n = 18), hypereosinophilic syndrome (n = 2), hyper-IgE syndrome (n = 6), and helminth infection (n = 4). Study 2: Blood was obtained from allergic subjects in a clinical trial of omalizumab before and during study drug treatment. Monocyte surface Fc?RI expression was measured using flow cytometry. Results Fc?RI expression was significantly greater in the CD2high vs. CD2low monocyte subsets (31% vs. 1.9% median Fc?RI+, respectively). In asthmatic and non-atopic healthy control subjects, CD2low monocytes expressed little or undetectable Fc?RI. In study 1, Fc?RI expression was highly correlated to serum IgE in the CD2high, but not in the CD2low monocyte subpopulation (R values of 0.67 and 0.41, respectively). In study 2, omalizumab but not placebo, caused a significant and sustained drop in Fc?RI expression within the CD2high monocyte subset. Conclusions CD2 defines a monocyte subset with high Fc?RI expression, the magnitude of which is highly correlated to serum IgE. As such, this new description of CD2high monocytes as Fc?RI bearing cells suggests that they may be potential targets of anti-IgE immunomodulatory therapies.

Cheng, Yuan Xiong; Foster, Barbara; Holland, Steven M.; Klion, Amy D.; Nutman, Thomas B.; Casale, Thomas B.; Metcalfe, Dean D.; Prussin, Calman

2006-01-01

357

Monocyte-to-Macrophage Differentiation  

PubMed Central

Although monocyte- and macrophage-derived molecules are known to promote extracellular matrix (ECM) disruption and destabilization, it is less appreciated that they also synthesize molecules contributing to ECM formation, stabilization, and function. We have identified and characterized the synthesis of proteoglycans and related proteins, some not previously known to be associated with macrophages. Proteoglycan extracts of [35S]sulfate- and 35S-trans amino acid-radiolabeled culture media from THP-1 monocytes induced to differentiate by treatment with phorbol myristate acetate revealed three major proteins of ?25, 90, and 100 kDa following chondroitin ABC lyase digestion. The 25-kDa protein was predominant for monocytes, whereas the 90- and 100-kDa proteins were predominant for macrophages. Tandem mass spectrometry identified (i) the 25-kDa core protein as serglycin, (ii) the 90-kDa core protein as inter-?-inhibitor heavy chain 2 (I?IHC2), and (iii) the 100-kDa core as amyloid precursor-like protein 2 (APLP2). Differentiation was also associated with (i) a >500-fold increase in mRNA for TNF-stimulated gene-6, an essential cofactor for heavy chain-mediated matrix stabilization; (ii) a >800-fold increase in mRNA for HAS2, which is responsible for hyaluronan synthesis; and (iii) a 3-fold increase in mRNA for versican, which interacts with hyaluronan. Biochemical evidence is also presented for an I?IHC2-APLP2 complex, and immunohistochemical staining of human atherosclerotic lesions demonstrates similar staining patterns for APLP2 and I?IHC2 with macrophages, whereas serglycin localizes to the underlying glycosaminoglycan-rich region. These findings indicate that macrophages synthesize many of the molecules participating in ECM formation and function, suggesting a novel role for these molecules in the differentiation of macrophages in the development of atherosclerosis.

Chang, Mary Y.; Chan, Christina K.; Braun, Kathleen R.; Green, Pattie S.; O'Brien, Kevin D.; Chait, Alan; Day, Anthony J.; Wight, Thomas N.

2012-01-01

358

HSV-2 Regulates Monocyte Inflammatory Response via the Fas/FasL Pathway  

PubMed Central

Monocytic cells represent important cellular elements of the innate and adaptive immune responses in viral infections. We assessed the role of Fas/FasL in promoting monocyte apoptosis during HSV-2 infection by using an in vitro model based on the murine RAW 264.7 monocytic cell line and an in vivo murine model of HSV-2 infection applied to C57BL6, MRL-Faslpr/J (Fas?/?) and C3-Faslgld/J (FasL?/?) mice. HSV-2 infection of the monocytic cell line led to early induction of apoptosis, with no protective expression of anti-apoptotic Bcl-2. HSV-2 infected monocytes up-regulated Fas and FasL expression early during in vitro infection but were susceptible to Fas induced apoptosis. The vaginal monocytes in the HSV-2 murine model of infection up-regulated FasL expression and were susceptible to Fas induced apoptosis. HSV-2 infection of Fas and FasL- deficient mice led to decreased apoptosis of monocytes and impaired recruitment of NK, CD4+ and CD8+ T cells within the infection sites. The vaginal lavages of HSV-2 infected Fas and FasL- deficient showed decreased production of CXCL9, CXCL10 and TNF-? in comparison to HSV-2 infected wild-type mice strain. The decreased recruitment of immune competent cells was accompanied by delayed virus clearance from the infected tissue. Triggering of the Fas receptor on HSV-2 infected monocytes in vitro up-regulated the expression of CXCL9 chemokines and the cytokine TNF-?. Our study provides novel insights on the role of Fas/FasL pathway not only in apoptosis of monocytes but also in regulating local immune response by monocytes during HSV-2 infection.

Krzyzowska, Malgorzata; Baska, Piotr; Orlowski, Piotr; Zdanowski, Robert; Winnicka, Anna; Eriksson, Kristina; Stankiewicz, Wanda

2013-01-01

359

Bovine Lymphocytic Leukemia: Studies of Etiology, Pathogenesis, and Mode of Transmission. Progress Report No. 19, June 1978-June 1979.  

National Technical Information Service (NTIS)

Bovine leukemia is believed to be caused by an oncogenic RNA virus designated bovine leukemia virus (BLV). The presence of BLV particles in lymphocyte cultures from leukemic cattle and cattle with a persistent lymphocytosis has been consistentily demonstr...

D. K. Sorensen

1979-01-01

360

Bovine Lymphocytic Leukemia: Studies of Etiology, Pathogenesis and Mode of Transmission. Progress Report No. 17, July 1976--October 1977.  

National Technical Information Service (NTIS)

The primary objective of the proposed research will be elucidation of the etiology and pathogenesis of bovine leukemia. We have consistently demonstrated C-type particles in mitogen stimulated lymphocyte cultures from leukemic cows and cows with a persist...

D. K. Sorensen

1977-01-01

361

Monocyte differentiation induced by co-culture with tumor cells involves RGD-dependent cell adhesion to extracellular matrix  

Microsoft Academic Search

Macrophages that infiltrate tumor tissues, or tumor-associated macrophages (TAMs), affect the malignant behaviors of tumor cells. In this study, we attempted to induce monocytes to differentiate into TAM-like cells producing matrix metalloproteinases (MMPs) by co-culture with tumor cells. When human monocytes were co-cultured for 3–7days with tumor cell lines, monocytes differentiated to produce MMP-9, accompanied by morphological changes. The in

Go Kamoshida; Ayaka Matsuda; Wakana Sekine; Hiromi Mizuno; Teruaki Oku; Saotomo Itoh; Tatsuro Irimura; Tsutomu Tsuji

362

Monoclonal antibodies identifying a novel T-Cell antigen and Ia antigens of human lymphocytes  

Microsoft Academic Search

We describe here two new monoclonal antibodies that react with surface antigens of human lymphocytes. Antibody 7.2 identified a determinant on the framework region of the human Ia antigen. It was cytotoxic for all cultured B-cell lines, normal B cells, and monocytes. The antibody was not cytotoxic for normal T cells or for established T leukemic cell lines. In immune

John A. Hansen; Paul J. Martin; Robert C. Nowinski

1980-01-01

363

Immunomodulatory Drugs Regulate HMGB1 Release from Activated Human Monocytes  

PubMed Central

Several HMGB1-specific antagonists have provided beneficial results in multiple models of inflammatory disease–preclinical trials including arthritis. Since no HMGB1-specific targeted therapy has yet reached the clinic, we have performed in vitro studies to investigate whether any of a selection of well-established antirheumatic drugs inhibit HMGB1 release as part of its mode of action. Freshly purified peripheral blood monocytes from healthy donors were stimulated in cultures with LPS and IFN? to cause HMGB1 and TNF release detected in ELISPOT assays. Effects on the secretion were assessed in cultures supplemented with dexamethasone, cortisone, chloroquine, gold sodium thiomalate, methotrexate, colchicine, etanercept or anakinra. Pharmacologically relevant doses of dexamethasone, gold sodium thiomalate and chloroquine inhibited the extracellular release of HMGB1 in a dose-dependent mode. Immunostaining demonstrated that dexamethasone caused intracellular HMGB1 retention. No effects on HMGB1 secretion were observed in cultures with activated monocytes by any of the other studied agents. TNF production in LPS/IFN?-activated monocytes was readily downregulated by dexamethasone and, to some extent, by chloroquine and etanercept. We conclude that dexamethasone, gold sodium thiomalate and chloroquine share a capacity to inhibit HMGB1 release from activated monocytes.

Schierbeck, Hanna; Wahamaa, Heidi; Andersson, Ulf; Harris, Helena Erlandsson

2010-01-01

364

Immunotherapy with the use of tumor-infiltrating lymphocytes and interleukin-2 as adjuvant treatment in stage III non-small-cell lung cancer. A pilot study.  

PubMed

This study assesses the feasibility and toxicity of adoptive immunotherapy with tumor infiltrating lymphocytes and recombinant interleukin-2 in 29 patients who underwent resection for stage III non-small-cell lung cancer. In five patients cultures yielded no growth of tumor infiltrating lymphocytes. In the remaining 24 patients (stage IIIa, 14 cases; stage IIIb, 10 cases) tumor infiltrating lymphocytes were in vitro expanded from surgically obtained tissue samples, including samples from both the tumor and surrounding lung. A number of tumor infiltrating lymphocytes, ranging from 4 to 70 billion cells, were reinfused intravenously 4 to 6 weeks after operation. Interleukin-2 was administered subcutaneously at escalating does for 2 weeks and then at reduced doses for 2 to 3 months. Median survival was 14 months, and the 2-year survival was 40%. Three patients remain alive and disease-free at more than 2 years after operation. Two of these patients did not have complete resection at thoracotomy. Multivariate analysis showed no correlation between the factor of incomplete resection and survival. Intrathoracic recurrence without concomitant distant failure was documented in two patients only and none of the patients with incomplete resection (12 cases) had relapse within the thorax. The present experience demonstrates that adoptive immunotherapy may be applied with safety in patients operated on for stage III non-small-cell lung cancer and suggests that it can be useful, notably in patients with locally advanced disease. PMID:7776685

Ratto, G B; Melioli, G; Zino, P; Mereu, C; Mirabelli, S; Fantino, G; Ponte, M; Minuti, P; Verna, A; Noceti, P

1995-06-01

365

Comparative studies on cytotoxic and genotoxic effects of two organic mercury compounds in lymphocytes and gastric mucosa cells of Sprague-Dawley rats  

SciTech Connect

Human lymphocytes (HL) as well as lymphocytes (RL), hepatocytes (RH), and gastric mucosa cells (GM) of Sprague-Dawley rats were treated in vitro for 1 h with methylmercury chloride (MMC, 0.5 -4 [mu]g/ml) and dimethylmercury (DMM, 5-40 [mu]g/ml). The cytotoxicity of the two organic mercury compounds was assessed by dye exclusion, and the extent of induced DNA fragmentation was measured with a single-cell microgel electrophoresis assay. Both MMC and DMM induced DNA damage and cytotoxicity in a dose-related manner in HL, RL, and GM. MMC was more effective in causing a significant increase in median DNA migration than DMM at doses yielding approximately the same degree of cytotoxicity. In rat hepatocytes the MMC-induced DNA damage was, however, lower than in the other cells. An analysis of repair kinetics following exposure to 2 [mu]g/ml MMC was carried out in human lymphocytes obtained from an adult male donor. The bulk of DNA repair occurred 90 min after in vitro exposure, and it was about complete by 120 min following cessation of exposure. Finally, in order to have a basis for extrapolating to the human situation, in vivo studies were performed with Sprague-Dawley rats, also assessing the DNA damage and cytotoxicity in the lymphocytes and gastric mucosa cells. These in vivo results after oral exposure may be directly compared to the in vitro data obtained in the same cells. 27 refs., 9 figs., 1 tab.

Betti, C.; Barale, R.; Pool-Zobel, B.L. (Univ. of Ferrara (Italy))

1993-01-01

366

Synergistic antitumor activity of tumor-infiltrating lymphocytes, interleukin 2, and local tumor irradiation. Studies on the mechanism of action  

PubMed Central

The adoptive transfer of tumor-infiltrating lymphocytes (TIL) with the concomitant administration of IL-2 has been shown to mediate the regression of established 6- and 14-d murine hepatic and pulmonary metastases. For successful immunotherapy with TIL, however, pretreatment with either cyclophosphamide (CP) or whole body irradiation (WBX) was required. The exact mechanism of CP and WBX augmentation of TIL antitumor activity remains unknown, but the elimination of Ts cells has been frequently invoked as an explanation. To address this possibility and to determine if local tumor irradiation (LTX) could synergize with TIL as well as WBX, we investigated the effect of LTX on the therapeutic efficacy of TIL and IL-2 in the treatment of multiple 7-d murine hepatic metastases. Experiments studying the treatment of a weakly immunogenic murine adenocarcinoma, MC-38, showed prolonged survival of mice treated with the combination of IL-2, TIL, and either LTX or WBX, compared with treatment with radiation alone or radiation plus IL-2 controls (p less than 0.0001). In addition, therapy with LTX and IL-2 prolonged survival, compared with LTX administration alone, whereas therapy with WBX combined with IL-2 did not alter survival. This augmentation of TIL-mediated antitumor activity was dependent on the dose of radiation used. To assess the possibility that tumor-associated Ts cells inhibit the function of adoptively transferred TIL in animals with 7-d metastatic tumor and are eliminated by WBX and LTX, we repeated the above experiments leaving some tumor unirradiated. Mice underwent either LTX or limited LTX, which included only the right side of the liver (LTX1/2). The number of right- and left-sided metastases were then individually counted. These studies showed that the reduction in the number of right-sided metastases was identical between the two groups and that the presence of left-sided tumor in the LTX1/2 group did not suppress the observed antitumor activity of TIL against irradiated tumor. Additional evidence against the elimination of suppressor cells as an important mechanism in radiation-induced augmentation of TIL antitumor activity was provided by experiments studying the effectiveness of TIL in thymectomized, lethally irradiated, and reconstituted B mice. Unless CP was administered before the adoptive transfer of TIL, therapy with IL-2 and TIL in these B mice was ineffective in the absence of demonstrable T lymphocytes.(ABSTRACT TRUNCATED AT 400 WORDS)

1990-01-01

367

Lymphocyte infiltration and activation in iris-ciliary body and anterior chamber of mice in corneal allograft rejection  

PubMed Central

AIM To investigate the infiltration and activation of lymphocyte in iris-ciliary body and anterior chamber after allogenic penetrating keratoplasty (PK), for further revealing the role of iris-ciliary body in corneal allograft immune rejection. METHODS In the mice models of PK, BALB/C mice received orthotopic isografts (n =35) or C57BL/6 donor allografts (n =25). Grafts were examined daily for 3 weeks by slit-lamp microscopy and scored for opacity. The infiltration of CD4+ T lymphocyte in iris-ciliary body and anterior chamber was examined by immunohistology and the mRNA of CD80 and CD86 in both cornea graft and iris-ciliary body by RT-PCR was analyzed in allograft recipient at days 3, 6, 10 and the day when graft rejection occurred. Isograft recipients were examined as control at the corresponding time points. Transmission electron microscope was used to study the ultrastructure, especially cell infiltration, of iris-cilary body and corneal graft at day 3, 7 and the day when rejection occurred after allogenic PK. RESULTS Rejection was observed in all the allograft recipients followed more than 10 days, at a median time of 15 days (range 12-18 days), but not in any of isografts. CD4+ T cells were first detected at day 6 after transplantation in limbus and Ciliary body, and then in the stroma of recipient, iris, anterior chamber and corneal allograft with an increased number until graft rejection occurred. CD80 and CD86 mRNA were detected under RT-PCR examination in both graft and iris-ciliary body of allograft recipient, but not in any of isograft recipient. Three days after operation, lymphocytes and monocytes macrophages were visible in iris blood vessels and the anterior chamber, and vascular endothelial cell proliferation and activation were significant under transmission electron microscopy examination. At day 7, corneal endothelial cells became thinner. Lymphocytes and mononuclear macrophages were found with great number in the anterior chamber and adhered to the corneal endothelium. Blood vessels in iris increased and were filled with lymphocytes. And lymphocytes were detected to migrate through endothelial cell gap out of vessels. When allograft rejection occurred, macrophages attached to endothelial cells with large number of lymphocytes and macrophages infiltrating in iris. CONCLUSION Lymphocyte infiltration and activation occurred in iris-ciliary body after allogenic PK, and the lymphocytes could migrate from iris blood vessel to the anterior chamber, which might play an important role in corneal allograft immune rejection.

Wang, Fu-Hua; Chen, Min; Liu, Ting; Zang, Xin-Jie; Gong, Hua-Qing; Shi, Wei-Yun

2012-01-01

368

Circulating Monocytes Expressing CD31  

PubMed Central

To identify the roles of various circulating cells (eg, endothelial and/or stem and progenitor cells) in angiogenesis, we parabiosed a wild-type syngeneic mouse with a transgenic syngeneic green fluorescent protein mouse. Following the establishment of a common circulation between these parabionts, we investigated acute (7 to 10 days), subacute (2 to 3 weeks), and chronic (4 to 6 weeks) phases of angiogenesis in wild-type mice using wound healing, implanted gel foam fragments, and subcutaneous tumor assays, respectively. We found that under in vitro conditions, circulating murine monocytes expressed F4/80, CD31, and vascular endothelial growth factor receptor 2, but neither CD133 nor von Willebrand factor, whereas murine endothelial cells expressed CD31, vascular endothelial growth factor receptor 2, and von Willebrand factor, but neither CD133 nor F4/80. Immunofluorescence analysis revealed that green fluorescent protein-positive cells in the walls of new vessels in wounds, gel foam blocks, and tumors expressed both F4/80 and CD31, that is, macrophages. Pericytes, cells that express both CD31 and desmin, were found both in the walls of tumor-associated vessels and within tumors. Collectively, these data demonstrate that monocytes (ie, cells that express both CD31 and F4/80) may be recruited to the site of tissue injury and directly contribute to angiogenesis, reaffirming the close relationships between various cell types within the reticuloendothelial system and suggesting possible targets for anticancer treatments.

Kim, Sun-Jin; Kim, Jang-Seong; Papadopoulos, John; Wook Kim, Seung; Maya, Marva; Zhang, Fahao; He, Junquin; Fan, Dominic; Langley, Robert; Fidler, Isaiah J.

2009-01-01

369

Bovine lymphocytic leukemia: studies of etiology, pathogenesis and mode of transmission. Progress report, November 1, 1979-October 31, 1980  

SciTech Connect

The primary project objectives are to elucidate the cause(s) and early pathogenesis of the adult form of lymphosarcoma in cattle. This goal is to be accomplished through experimental transmission of the disease. For these studies large quantities of bovine leukemia virus (BLV) were propagated in short-term, mitogen stimulated, lymphocyte cultures. Cultures containing abundant BLV particles were pooled (33 liters total) and further processed by continuous flow, density gradient, ultracentrifugation. This higly concentrated, cell free, BLV preparation was then used as inoculum for 12 late stage bovine fetuses (inoculated in utero) and two newborn calves. Extensive monitoring studies have been carrid out on these inoculated animals to detect precancerous changes and to obtain a detailed description of the events preceding the development of lymphosarcoma. These extensive records on lymphosarcoma associated blood parameters have established that all of the inoculated animals became persistently BLV infected. However, after more than five years of incubation, no cases of lymphosarcoma developed. Consequently, during the past seven months, five of these well characterized animals have been subjected to frequent BLV re-exposure in order to study BLV-host interactions in previously infected adults and to potentially accelerate tumor formation in these animals.

Sorensen, D.K.

1980-06-01

370

Ionizing Radiation and Risk of Chronic Lymphocytic Leukemia in the 15-Country Study of Nuclear Industry Workers  

PubMed Central

In contrast to other types of leukemia, chronic lymphocytic leukemia (CLL) has long been regarded as non-radiogenic, i.e. not caused by ionizing radiation. However, the justification for this view has been challenged. We therefore report on the relationship between CLL mortality and external ionizing radiation dose within the 15-country nuclear workers cohort study. The analyses included, in seven countries with CLL deaths, a total of 295,963 workers with more than 4.5 million person-years of follow-up and an average cumulative bone marrow dose of 15 mSv; there were 65 CLL deaths in this cohort. The relative risk (RR) at an occupational dose of 100 mSv compared to 0 mSv was 0.84 (95% CI 0.39, 1.48) under the assumption of a 10-year exposure lag. Analyses of longer lag periods showed little variation in the RR, but they included very small numbers of cases with relatively high doses. In conclusion, the largest nuclear workers cohort study to date finds little evidence for an association between low doses of external ionizing radiation and CLL mortality. This study had little power due to low doses, short follow-up periods, and uncertainties in CLL ascertainment from death certificates; an extended follow-up of the cohorts is merited and would ideally include incident cancer cases.

Vrijheid, Martine; Cardis, Elisabeth; Ashmore, Patrick; Auvinen, Anssi; Gilbert, Ethel; Habib, Rima R.; Malker, Hans; Muirhead, Colin R.; Richardson, David B.; Rogel, Agnes; Schubauer-Berigan, Mary; Tardy, Helene; Telle-Lamberton, Maylis

2014-01-01

371

Expression of CD147 on monocytes\\/macrophages in rheumatoid arthritis: its potential role in monocyte accumulation and matrix metalloproteinase production  

Microsoft Academic Search

Monocytes\\/macrophages play an important role in rheumatoid arthritis (RA) pathogenesis. They can activate fibroblasts through many molecules, including IL-1 and tumor necrosis factor-alpha, but there have been very few reports on the role of CD147 in RA. In our study, the results of flow cytometry reveal that the mean fluorescence intensity (MFI) of CD147 expression on CD14+ monocytes of peripheral

Ping Zhu; J