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Mature Macrophages (mature + macrophage)

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Medical Sciences100%

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Increased expression of Fc, receptors II and III on macrophages of rheumatoid arthritis patients results in higher production of tumor necrosis factor , and matrix metalloproteinase

ARTHRITIS & RHEUMATISM, Issue 4 2003
Arjen B. Blom
Objective To evaluate Fc, receptor (Fc,R) expression on synovial macrophages from rheumatoid arthritis (RA) patients and to determine whether this expression correlates with the production of the proinflammatory cytokines tumor necrosis factor , (TNF,), interleukin-1, (IL-1,), IL-12, and matrix metalloproteinase 1 (MMP-1). We also sought to determine whether mature macrophages from RA patients express aberrant levels of Fc,RI, Fc,RII, and Fc,RIII, and to determine the production of inflammatory mediators after immune complex (IC) stimulation. Methods Immunohistochemistry was performed on cryostat sections of synovial biopsy specimens obtained from 27 RA patients and 5 controls. Fc,R I, II, and III were detected, as well as the proinflammatory mediators IL-1, TNF,, IL-12, and MMP-1. Monocytes were isolated from the blood of 10 RA patients and 10 healthy controls and cultured for 7 days with macrophage colony-stimulating factor to obtain macrophages. Using fluorescence-activated cell sorting, the expression of Fc,RI, Fc,RII, and Fc,RIII was determined. On day 7, macrophages were stimulated with heat-aggregated gamma globulins (HAGGs) for 24 hours. Production of cytokines was measured using enzyme-linked immunosorbent assay, and production of gelatinases/collagenases was measured by degradation of fluorescent gelatin. Results Immunohistochemistry showed higher Fc,RII and Fc,RIII expression in RA synovium than in controls. Fc,RII and Fc,RIII, but not Fc,RI, were highly correlated with the number of synovial macrophages. Consistent with this, TNF, expression correlated positively with Fc,RIII expression. Moreover, MMP-1 expression strongly correlated with Fc,R I, II, and III expression. Mature macrophages from RA patients showed significantly enhanced expression of Fc,RII and Fc,RIII compared with controls. Twenty-four hours after stimulation of RA macrophages with HAGGs, significantly higher production of TNF, and gelatinase/collagenase was measured. Conclusion RA synovium and mature RA macrophages express significantly elevated levels of Fc,RII and Fc,RIII, resulting in much higher production of TNF, and gelatinase/collagenase after IC stimulation. These data suggest that disturbed expression of Fc,R on mature synovial macrophages is involved in the pathology of RA. [source]

Effect of reactive oxygen intermediaries on the viability and infectivity of Mycobacterium lepraemurium

INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 3 2007
Kendy Wek-Rodriguez
Summary Murine leprosy is a natural disease of the mouse, the most popular model animal used in biomedical research; the disease is caused by Mycobacterium lepraemurium (MLM), a successful parasite of macrophages. The aim of the study was to test the hypothesis that MLM survives within macrophages because it highly resists the toxic effects of the reactive oxygen intermediaries produced by these cells in response to infection by the microorganism. MLM cells were incubated in the presence of horseradish peroxidase (HRPO),H2O2,halide for several periods of time. The peroxidative effect of this system was investigated by assessing the changes occurred in (a) lipid composition; (b) viability; and (c) infectivity of the microorganism. Changes in the lipid composition of peroxidated- vs. intact-MLM were analysed by thin layer chromatography. The effect of the peroxidative system on the viability and infectivity of MLM was measured by the alamar blue reduction assay and by its ability to produce an infection in the mouse, respectively. Peroxidation of MLM produced drastic changes in the lipid envelope of the microorganism, killed the bacteria and abolished their ability to produce an in vivo infection in the mouse. In vitro, MLM is highly susceptible to the noxious effects of the HRPO,H2O2,halide system. Although the lipid envelope of MLM might protect the microorganism from the peroxidative substances produced at ,physiological' concentrations in vivo, the success of MLM as a parasite of macrophages might rather obey for other reasons. The ability of MLM to enter macrophages without triggering these cells' oxidative response and the lack of granular MPO in mature macrophages might better explain its success as an intracellular parasite of these cells. [source]

Increased expression of Fc, receptors II and III on macrophages of rheumatoid arthritis patients results in higher production of tumor necrosis factor , and matrix metalloproteinase

ARTHRITIS & RHEUMATISM, Issue 4 2003
Arjen B. Blom
Objective To evaluate Fc, receptor (Fc,R) expression on synovial macrophages from rheumatoid arthritis (RA) patients and to determine whether this expression correlates with the production of the proinflammatory cytokines tumor necrosis factor , (TNF,), interleukin-1, (IL-1,), IL-12, and matrix metalloproteinase 1 (MMP-1). We also sought to determine whether mature macrophages from RA patients express aberrant levels of Fc,RI, Fc,RII, and Fc,RIII, and to determine the production of inflammatory mediators after immune complex (IC) stimulation. Methods Immunohistochemistry was performed on cryostat sections of synovial biopsy specimens obtained from 27 RA patients and 5 controls. Fc,R I, II, and III were detected, as well as the proinflammatory mediators IL-1, TNF,, IL-12, and MMP-1. Monocytes were isolated from the blood of 10 RA patients and 10 healthy controls and cultured for 7 days with macrophage colony-stimulating factor to obtain macrophages. Using fluorescence-activated cell sorting, the expression of Fc,RI, Fc,RII, and Fc,RIII was determined. On day 7, macrophages were stimulated with heat-aggregated gamma globulins (HAGGs) for 24 hours. Production of cytokines was measured using enzyme-linked immunosorbent assay, and production of gelatinases/collagenases was measured by degradation of fluorescent gelatin. Results Immunohistochemistry showed higher Fc,RII and Fc,RIII expression in RA synovium than in controls. Fc,RII and Fc,RIII, but not Fc,RI, were highly correlated with the number of synovial macrophages. Consistent with this, TNF, expression correlated positively with Fc,RIII expression. Moreover, MMP-1 expression strongly correlated with Fc,R I, II, and III expression. Mature macrophages from RA patients showed significantly enhanced expression of Fc,RII and Fc,RIII compared with controls. Twenty-four hours after stimulation of RA macrophages with HAGGs, significantly higher production of TNF, and gelatinase/collagenase was measured. Conclusion RA synovium and mature RA macrophages express significantly elevated levels of Fc,RII and Fc,RIII, resulting in much higher production of TNF, and gelatinase/collagenase after IC stimulation. These data suggest that disturbed expression of Fc,R on mature synovial macrophages is involved in the pathology of RA. [source]

Macrophage Stimulating Protein (MSP) evokes superoxide anion production by human macrophages of different origin

BRITISH JOURNAL OF PHARMACOLOGY, Issue 6 2001
Sandra Brunelleschi
Macrophage Stimulating Protein (MSP), a serum factor related to Hepatocyte Growth Factor, was originally discovered to stimulate chemotaxis of murine resident peritoneal macrophages. MSP is the ligand for Ron, a member of the Met subfamily of tyrosine kinase receptors. The effects of MSP on human macrophages and the role played in human pathophysiology have long been elusive. We show here that human recombinant MSP (hrMSP) evokes a dose-dependent superoxide anion production in human alveolar and peritoneal macrophages as well as in monocyte-derived macrophages, but not in circulating human monocytes. Consistently, the mature Ron protein is expressed by the MSP responsive cells but not by the unresponsive monocytes. The respiratory burst evoked by hrMSP is quantitatively higher than the one induced by N-formylmethionyl-leucyl-phenylalanine and similar to phorbol myristate acetate-evoked one. To investigate the mechanisms involved in NADPH oxidase activation, leading to superoxide anion production, different signal transduction inhibitors were used. By using the non selective tyrosine kinase inhibitor genistein, the selective c-Src inhibitor PP1, the tyrosine phosphatase inhibitor sodium orthovanadate, the phosphatidylinositol 3-kinase inhibitor wortmannin, the p38 inhibitor SB203580, the MEK inhibitor PD098059, we demonstrate that hrMSP-evoked superoxide production is mediated by tyrosine kinase activity, requires the activation of Src but not of PI 3-kinase. We also show that MAP kinase and p38 signalling pathways are involved. These results clearly indicate that hrMSP induces the respiratory burst in human macrophages but not in monocytes, suggesting for the MSP/Ron complex a role of activator as well as of possible marker for human mature macrophages. British Journal of Pharmacology (2001) 134, 1285,1295; doi:10.1038/sj.bjp.0704356 [source]