Identification of immunoglobulins and complement in rheumatoid articular collagenous tissues

Cooke, T. D. V.; Hurd, Eric R.; Jasin, Hugo E.; Bienenstock, John; Ziff, Morris

doi:10.1002/art.1780180603

Cited by 183 publications

(70 citation statements)

References 22 publications

(5 reference statements)

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“…Further studies by us and others revealed that the activated chondrocytes in the superficial layer of cartilage were responsible for much of the NO produced by this tissue (8,9). These findings, coupled to previous studies showing the presence of immune complexes trapped on the surface of rheumatoid cartilage (20), suggested that in this disease, large concentrations of oxygen radicals and NO may coexist at the cartilage surface. Finally, recent studies in our laboratory indicated that H 2 O 2 , and the product of oxidation of NO, nitrite salts, as well as ONOO, were able to cross-link and nitrosate immunocomplexes (10).…”

Section: Discussionmentioning

confidence: 51%

Inflammatory Properties of IgG Modified by Oxygen Radicals and Peroxynitrite

Uesugi

Yoshida

Jasin

2000

The Journal of Immunology

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In inflammatory arthritis, there is evidence indicating that the affected tissues produce large amounts of oxygen-free radicals and NO. Herein, we examine the biologic effects of exposure of IgG to hypochlorous acid (HOCl) and peroxynitrite (ONOO). The concentrations of IgG modified by chlorination and nitrosation were measured in synovial fluids from inflammatory and noninflammatory arthritis. Human IgG was exposed to increasing concentrations of HOCl and ONOO, and the resulting products were tested for complement component binding; binding to FcγRI; activation of polymorphonuclear neutrophils; effect on the Ab-combining site of Abs; and in vivo inflammatory activity in a rabbit model of acute arthritis. Rheumatoid synovial fluids contained significantly greater concentrations of nitrosated and chlorinated IgG compared with ostearthritic specimens. In vitro exposure of human IgG to HOCl and ONOO resulted in a concentration-dependent decrease in C3 and C1q fixation. The decrease in Fc domain-dependent biologic functions was confirmed by competitive binding studies to the FcγRI of U937 cells. HOCl-treated IgG monomer was 10 times less effective in competing for binding compared with native IgG, and ONOO-treated IgG was 2.5 times less effective. The modified IgGs were also ineffective in inducing synthesis of H2O2 by human PMN. The Ag-binding domains of IgG also showed a concentration-dependent decrease in binding to Ag. The ability of the modified IgGs to induce acute inflammation in rabbit knees decreased 20-fold as gauged by the intensity of the inflammatory cell exudates. These studies clarify the modulating role of biological oxidants in inflammatory processes in which Ag-autoantibody reactions and immune complex pathogenesis may play an important role.

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Section: Discussionmentioning

confidence: 51%

Inflammatory Properties of IgG Modified by Oxygen Radicals and Peroxynitrite

Uesugi

Yoshida

Jasin

2000

The Journal of Immunology

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“…Numerous aspects of this model have been shown to resemble rheumatoid disease, including in both the immunofluorescent demonstration of immunoglobulins and complement components in ACT surfaces (2,3,15,22). Immuno-em studies of rheumatoid ACT have suggested the presence of IgG and IgM (23).…”

Section: Discussionmentioning

confidence: 99%

Pathogenesis of chronic inflammation in experimental ferritin‐induced arthritis.

Ohno¹,

Tateishi²,

Td³

1978

Arthritis & Rheumatism

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The earliest and most severe changes in articular collagenous tissues (ACT) occur within 24 hours of antigen challenge and are associated with and are possibly secondary to maximal immune complex deposition in ACT surfaces. The immuno-electron microscopic (immuno-em) staining characterizes the ferritin as aggregates with antibody and suggests its occurrence and deposition as a preformed immune complex. These data indicate a direct interaction between immune complexes and collagenous matrix which could relate to both antigen In this model for rheumatoid arthritis (RA) ( I ,2) persistence of the inducing antigen (Ag) in association with rabbit immunoglobulin (Ig) and complement components (p,,) has been demonstrated in a surface relationship of the articular collagenous tissues (ACT), i.e. hyaline cartilage, intra-articular ligaments, and the menisci of the knee (3). The specificity of antibody synthesis in synovial cultures suggested that the local immune response was directed at and maintained by the complexed Ag in ACT (2). The fact that detailed information of the nature, form, and site of these complexes, as well as knowledge of changes in ACT matrix, was not known prompted this study using immuno-em techniques. Ferritin was chosen as the antigen as it contains more than 20% of iron by weight, is easily detected by its characteristic em appearance (4), and was shown in a preliminary study to be a suitable protein antigen (5,6). MATERIALS AND METHODSAnimals. New Zealand white rabbits of either sex weighing 2-3 kg were used. They were fed regular Purina Chow and water ad libitum.

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“…Enzymes released in the immediate proximity of cartilage are probably of greater importance. They may originate in granulation tissue pannus, or as a consequence of phagocytosis or reversed endocytosis associated with immune complex deposition in the superficial collagenous layer of cartilage (13,14). Such sources of enzymes, however, would only provide a partial explanation for matrix destruction in that proteoglycan depletion may, at times, be observed in midzone and deeper regions of cartilage, which are anatomically divorced from events that occur in the superficial layer (15).…”

Section: Modulation Of Cartilage Destruction By Select Nonsteroidal Amentioning

confidence: 99%

Modulation of cartilage destruction by select nonsteroidal antiinflammatory drugs

Herman

Appel

Hess

1987

Arthritis & Rheumatism

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Non‐enzymatic factors produced by synovial tissue can potentially mediate cartilage destruction by inducing the synthesis and release of matrix‐degrading proteinases from chondrocytes. Pharmacologic control of this process is of potential clinical relevance. The in vitro effect of therapeutic concentrations of select nonsteroidal antiinflammatory drugs on the synthesis and activity of catabolism‐inducing cytokines produced by 6‐day explant cultures of osteoarthritic and rheumatoid synovial tissue was studied. Piroxicam regularly suppressed such factor synthesis by both types of tissue without significantly affecting total protein synthesis. This did not occur using sodium salicylate or indomethacin in osteoarthritis tissue cultures and was observed only occasionally in rheumatoid arthritis cultures. None of the nonsteroidal antiinflammatory drugs studied consistently blocked catabolism‐inducing activity in osteoarthritis tissue, whereas piroxicam more consistently inhibited activity produced by rheumatoid arthritis tissue. Results suggest that the catabolism‐inducing factors produced by the 2 tissue sources may differ.

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Identification of immunoglobulins and complement in rheumatoid articular collagenous tissues

Abstract: Ninety-three patients with a variety of joint diseases were studied for evidence of immune complexes in articular collagenous tissues. Frozen sections of freshly obtained biopsies of hyaline articular cartilage and menisci were stained with fluoresceinated

Cited by 183 publications

References 22 publications

Inflammatory Properties of IgG Modified by Oxygen Radicals and Peroxynitrite

Inflammatory Properties of IgG Modified by Oxygen Radicals and Peroxynitrite

Pathogenesis of chronic inflammation in experimental ferritin‐induced arthritis.

Modulation of cartilage destruction by select nonsteroidal antiinflammatory drugs

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