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A crucial role for macrophages in the pathology of K/B × N serum-induced arthritis

European Journal of Immunology, ISSN: 0014-2980, Vol: 35, Issue: 10, Page: 3064-3073
2005
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Article Description

Autoantibodies in the form of immune complexes are known to be crucial mediators in initiating inflammation in a variety of autoimmune diseases. This has been well documented in the anti-collagen II antibody-induced arthritis animal model for a long time now. Recently, in the K/B × N mouse model (the F1 of the TCR-transgenic KRN and the diabetic NOD mice), anti-glucose-6-phosphate isomerase (GPI) autoantibodies have been shown to induce arthritis. Experimental work in the K/B × N model demonstrated key roles of autoantigenic immune complexes activating the alternative pathway of complement, the subsequent association with C5aR and FcγRIII-mediated cell activation and production of the inflammatory cytokines IL-1 and TNF-α, finally leading to joint destruction. The presence of high amounts of inflammatory cytokines and matrix-degrading proteases at sites of inflammation obviously put the cytokine-producing macrophages as the next target for investigation in this model. Here, we show that mice depleted of macrophages by clodronate liposome treatment are completely resistant to K/B × N serum-induced arthritis. Reconstituting clodronate liposome-treated mice with macrophages from naive animals could reverse this resistance. Also, we found that deficiencies in the Wiskott-Aldrich syndrome protein and CD40, which are both implicated in macrophage activation, chemotaxis and phagocytosis, are not essential in serum-induced arthritis. Mast cell degranulation was seen in arthritogenic serum-treated mice even in the absence of macrophages, possibly suggesting that mast cell degranulation/activation acts hierarchically before macrophages in the inflammatory cascade of anti-GPI antibody-induced arthritis. © 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Bibliographic Details

Solomon, Samuel; Rajasekaran, Narendiran; Jeisy-Walder, Elvira; Snapper, Scott B; Illges, Harald

Wiley

Medicine; Immunology and Microbiology

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