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

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

Research output: Contribution to journalArticlepeer-review

110 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)3064-3073
Number of pages10
JournalEuropean Journal of Immunology
Issue number10
StatePublished - Oct 2005
Externally publishedYes


  • Arthritis
  • CD40
  • Macrophages
  • Mast cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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