Using properdin-deficient and wild-type mice, we have investigated the role of properdin in development and progression of zymosan-induced arthritis. At the initial phase of local, zymosan-induced inflammation, properdin-deficient and wild-type mice showed bone erosion, proteoglycan loss and cell infiltration. Compared to wild-type, properdin-deficient mice had reduced C5a and IL-6 but similar synovial TNF-alpha and sRANKL levels. Both groups showed a systemic immune response. Elevated IFN-gamma production and STAT1 signaling in splenocytes and a shift to Th1 response in popliteal lymph nodes were observed in properdin-deficient mice. Properdin-deficient mice had significantly less circulating zymosan-specific IgG antibodies than wild-type. In the chronic phase, the lack of properdin resulted in significant proteoglycan loss in the joints and lower cartilageneous STAT1 expression. The level of synovial C5a on day 30 was comparable in both groups, but C5aR staining was more apparent in the joints of properdin-deficient mice. Our data show that properdin is an important player in processes involved in inflammatory joint degradation.
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