Role of Fc receptor gamma chain in inflammation and cartilage damage during experimental antigen-induced arthritis

Objective. To study the role of Fc receptor (FcR) gamma chain in inflammati on and cartilage destruction during antigen-induced arthritis (AIA). Methods. FcR gamma-/- mice and controls were immunized with methylated bovi ne serum albumin (mBSA) in Freund's complete adjuvant, followed by inductio n of arthritis by local injection of mBSA into the right knee joint. Joint inflammation was studied by Tc-99m uptake and by histology. Breakdown of pr oteoglycans from the cartilage matrix was determined by loss of red stainin g in Safranin O-stained knee joint sections, and matrix metalloproteinase ( MMP)-mediated aggrecan degradation was determined by immunolocalization usi ng anti-VDIPEN antibodies. Chondrocyte death was measured by determining em pty lacunae in hematoxylin-stained sections and with the TUNEL assay in cry ostat sections. Erosion was detected as ruffling of the cartilage surface. Results. Joint swelling, as measured by 99mTc uptake on days 1, 3, and 7,wa s significantly decreased in FcR gamma-/- mice compared with controls. On d ay 7 after AIA induction, sustained joint inflammation, as seen histologica lly, was not significantly lower in FcR gamma-/- deficient mice. In various cartilage layers (femur, tibia, patella) of control arthritic knee joints, marked depletion of proteoglycans (40-70%), chondrocyte death (25-50%), an d mild surface erosion were found. In FcR gamma-/- knee joints, depletion o f proteoglycans was comparable (40-70%), Strikingly, chondrocyte death and matrix erosion were absent, Furthermore, MMP-induced aggrecan neoepitopes, which were abundantly found in controls, were also absent in FcR gamma-/-, Nevertheless, latent MMPs were present in the cartilage matrix as seen in A PMA-activated patellae. Conclusion. FcR gamma chain is involved in the severity of acute and sustai ned inflammation and is a crucial factor in cartilage erosion during AIA, p robably by regulating activation of latent MMPs present in the cartilage ma trix.