Immunolocalization of inducible nitric oxide synthase in synovium and cartilage in rheumatoid arthritis and osteoarthritis |
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Authors: | Grabowski PS; Wright PK; Van 't Hof RJ; Helfrich MH; Ohshima H; Ralston SH |
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Institution: | Department of Medicine and Therapeutics, University of Aberdeen. |
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Abstract: | Nitric oxide has been implicated as a mediator of inflammatory arthritis,
and recent work has shown that pro-inflammatory cytokines stimulate NO
production in vitro by activation of the inducible nitric oxide synthase
(iNOS) pathway. In order to identify the cellular sources of NO production
within the joint, we have used immunohistochemical techniques to study the
distribution of iNOS in synovium and cartilage from normal and diseased
joints. iNOS was most strongly expressed in the synovial lining layer,
subsynovium, vascular smooth muscle and chondrocytes from patients with
rheumatoid arthritis (RA). Analysis of serial sections, coupled with double
immunofluorescent staining, showed that the CD68+ macrophages in the
synovial lining layer and, to a lesser extent, fibroblasts were the
predominant source of iNOS within synovium, whereas T cells, B cells and
neutrophils were negative. A similar pattern of iNOS staining was seen in
osteoarthritis, but fewer cells were iNOS positive and the intensity of
staining, particularly in cartilage, was much weaker than in RA. In
contrast, no evidence of iNOS was detected in non- inflammatory synovium or
in cartilage derived from normal joints (fractured neck of femur). In
conclusion, these data support the hypothesis that synovium and cartilage
are important sources of increased NO production in patients with
inflammatory arthritis. Localization of iNOS at these sites within the
inflamed joint raises the possibility that increased local production of NO
may contribute to the pathogenesis of inflammatory arthritis by increasing
synovial blood flow and by modulating cellular function within synovium and
articular cartilage.
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