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Activating FcγRIII determines cartilage destruction during immune complex arthritis but not in the presence of T-cell immunity
Arthritis Research & Therapy volume 4, Article number: 42 (2002)
We have recently shown that activating Fcγ receptors determine metalloproteinase (MMP)-induced cartilage destruction, seen in various murine models of arthritis mediated by immune complexes (IC). In the mouse, two activating FcγR (FcγRI and FcγRIII) which bind IC have been described. In this study, we investigated the role of activating FcγRIII in MMP-mediated cartilage destruction in two different models of experimental arthritis, one induced only by ICs and the second by ICs and T cells.
Mice made deficient for FcγRIII and their wildtype controls(C57BL/6) were used. Immune complex arthritis (ICA) was induced by injecting lysozyme directly into the knee joint of mice, which had previously been given antilysozyme intravenously. T cell-mediated IC-mediated IC-arthritis (AIA) was induced by immunizing mice with mBSA in CFA and injection of the antigen directly into the knee joint, 3 weeks after immunization. Cartilage destruction was studied by immunolocalisation of MMP-mediated neoepitopes (VDIPEN) and matrix erosion in total knee joint sections. Adaptive cellular cells (T cells) and humoral immunity (anti-mBSA antibodies) were investigated using lymphocyte stimulation assay and ELISA.
ICA induced in naive C57BL/6 knee joints showed florid inflammation at day 1 and 3. MMP-mediated cartilage destruction and matrix erosion was moderate at day 3. When ICA was induced in knee joints of FcγRIII deficient mice, joint inflammation, MMP-mediated cartilage destruction and erosion was significantly lower (respectively 95, 100 and 80%). In addition, AIA was induced in FcγRIII-/-. Immunisation of FcγRIII-/- did not alter adaptive cellular immunity or humoral immunity against mBSA if compared to wildtype controls. Induction of AIA showed similar swelling at day 1, 3 and 7. At day 7, histology showed severe chronic joint inflammation not different from controls. MMP-mediated cartilage destruction and erosion was also similar to wildtype controls. In contrast, AIA induction in knee joints of Fcg chain-/- (which lack both functional FcγRI and III), MMP-mediated cartilage destruction and erosion was completely prevented.
FcγRIII is the dominant activating receptor in MMP-mediated cartilage destruction and erosion during arthritis merely induced by immune complexes. In T cell driven immune complex arthritis, however, FcγRIII is not important or redundant.
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van Lent, P., Nabbe, K., Blom, A. et al. Activating FcγRIII determines cartilage destruction during immune complex arthritis but not in the presence of T-cell immunity. Arthritis Res Ther 4, 42 (2002). https://doi.org/10.1186/ar484
- Knee Joint
- Humoral Immunity
- Joint Inflammation
- Cartilage Destruction
- Stimulation Assay