Critical role of peripheral blood phagocytes and the involvement of complement in tumour necrosis factor enhancement of passive collagen-arthritis.
Studies have implicated tumour necrosis factor-alpha (TNF-alpha) in type-II collagen (CII)-induced arthritis (CIA), a well established animal model of human rheumatoid arthritis. Precisely how TNF is involved in CIA is not yet clear. In this study the effects of TNF on CIA were examined, independent of its potential effects on the immune response, by performing peri-articular injection of TNF in combination with passive immunization of rats. A sub-arthritic dose (5 mg) of affinity-purified anti-CII IgG, which alone was insufficient to induce spontaneous clinical arthritis, was used throughout the study. Obvious clinical arthritis that persisted for several days was rapidly induced by injections of 100 ng TNF into hindpaws of rats that were passively immunized shortly before the TNF injection. Injections of TNF in non-immunized control rats did not induce clinical arthritis, nor did buffer-only injections in passively immunized controls. The clinical arthritic response was a local phenomenon, limited only to the TNF-injected hindpaws. No swelling was observed in the opposite, buffer-injected hindpaws, indicating the effects of TNF were not systemic. Depletion of peripheral blood phagocytes with anti-rat neutrophil antiserum before passive immunization completely abolished the ability of TNF to induce clinical arthritis, identifying phagocytic cells as the essential target cells in evoking this arthritic response. A role for complement activation was also demonstrated in this model through the use of a soluble recombinant version of CD35, the cell surface complement receptor type-1 (sCR1, BRL55730), which significantly reduced TNF-induced arthritis in phagocyte-replete rats.
Fava
R A
RA
Department of Veterans Affairs Medical Center, White River Jct., VT.
Gates
C
C
Townes
A S
AS
D000818:Animals; D001168:Arthritis / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D003094:Collagen / Q000276:immunology; D003167:Complement Activation; D003165:Complement System Proteins / Q000502:physiology*; D005260:Female; D007116:Immunization, Passive; D009504:Neutrophils / Q000276:immunology / Q000473:pathology; D010586:Phagocytes / Q000276:immunology* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D017463:Receptors, Complement 3b / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology* / Q000502:physiology
D017463:Receptors, Complement 3b; D014409:Tumor Necrosis Factor-alpha; D003094:Collagen; D003165:Complement System Proteins