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Rheumatoid Arthritis is a Lining Cell Disease: An Evolving Concept

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Rheumatoid arthritis (RA) is a chronic inflammatory disease affecting predominantly lining structures, including synovial tissue, tendon sheaths, bursae, pleura, and pericardium. Characteristically, these tissues contain large numbers of macrophages, suggesting that these cells are crucial in the pathogenesis of the disease. Data obtained by us and by others have indicated that phagocytic lining cells are essential for disease onset and expression. Removal of synovial lining cells by intra-articular injection of apoptosis-inducing clodronate liposomes prevents joint inflammation in murine arthritis models, and pilot data suggest that these liposomes can be succesfully used in humans. The degree of monocyte/macrophage (but not of T-cell) infiltration in rheumatoid joints has been reported to correlate with both disease activity and progression of joint destruction in rheumatoid arthritis (RA). Recent studies have shown that intrinsic macrophage characteristics may determine an individual's susceptibility to develop arthritis. Murine collagen-induced arthritis-susceptible mouse strains were shown to have markedly higher expression of FcK RII/III by macrophages than nonsusceptible strains (Blom, 1999). In human RA, we found that activated monocyte-derived macrophages produce significantly higher IL-8 mRNA levels than those in controls, pointing to an innate hyper-responsiveness of these cells in this disease. The central role of lining macrophages in the pathogenesis of RA has therapeutic consequences in terms of targeting these cells and/or their proinflammatory products.


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van de Putte, L.B., van Lent, P., Rodenburg, R. et al. Rheumatoid Arthritis is a Lining Cell Disease: An Evolving Concept. Arthritis Res Ther 1 (Suppl 1), S17 (1999).

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