Activation of the monocyte-macrophage system in rheumatoid arthritis

Journal/Book: Z Rheumatol 1999; 58:366. 1999;

Abstract: Prof. Dr. G. R. Burmester Department of Rheumatology and Clinical Immunology Charité University Hospital Humboldt University of Berlin Rheumatoid arthritis is characterized by cartilage and bone destruction via pannus formation. It is also a systemic disease where monocytes are known to play an important role in the inflammatory processes. To further investigate mechanisms of monocyte activation differential gene analysis appears to be a powerful tool. Thus we have differentially analyzed gene expression in activated monocytes from first (activated) and third (non-activated) leukapheresis preparations from an RA patient. Typical genes identified were IL-1Alpha -Beta IL-6 TNF-Alpha. Furthermore GRO-Alpha/melanoma growth-stimulatory activity MIP-2/GRO-Beta ferritin Alpha-1-antitrypsin lysozyme transaldolase EBER-1/BBER-2-associated-protein thrombospondin 1 an angiotensin receptor-II C-terminal homologue RNA polymerase-II elongation factor (elongin) 3 unknown (BSK-66 -80 -89) and homologues of functionally undefined genes (BSK-67 -83) were differentially expressed. Overexpression was confirmed for selected genes by semiquantitative PCR analysis in monocytes from RA patients versus healthy donors including IL-1-Beta the ATR-II homologue BSK-66 -67 and -89. To investigate the importance of monocytes in the synovial tissue and to take other cells in the synovial pannus into account especially fibroblasts who may modulate the destructive process essentially a representational difference analysis has been performed in whole synovial tissue between RA and OA. Furthermore a modified technique of semiquantitative PCR was used to verify these data and to analyze a group of genes possibly involved in the tissue homeostasis of cartilage. A preliminary analysis of 151 clones revealed that genes other than regulatory cytokines dominate the difference. Especially genes of effector functions like immunoglobulin and collagen type I are overrepresented. Furthermore receptors with immunoregulatory function like HLA-DR ... le

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