Figure 3.

Candidate proinflammatory functions of mast cells in synovitis. Mast cell effector functions suggest their participation in diverse pathogenic pathways in inflammatory arthritis, including leukocyte recruitment and activation, synovial fibroblast activation and hyperplasia, angiogenesis, and cartilage and bone destruction. Activated mast cells elaborate mediators potently capable of enhancing vasopermeability, inducing endothelial expression of adhesion molecules, recruiting circulating leukocytes, and activating infiltrating leukocytes as well as resident macrophages, thereby contributing to the early phases of inflammatory arthritis. In chronic synovitis, mast cells synthesize mitogens and cytokines that activate synovial fibroblasts, recruit macrophages, and promote the growth of new blood vessels, implicating them in synovial lining hyperplasia and pannus formation. Further, mast cells may participate in joint destruction by the induction of matrix metalloproteinases (MMPs) from fibroblasts, by activation of chondrocytes, and by direct and indirect promotion of osteoclast differentiation and activation. Because activated synovial fibroblasts demonstrate enhanced stem cell factor (SCF) expression, a potentially important positive feedback loop is established in which SCF promotes mast cell survival and proliferation, leading to the mastocytosis described in inflamed synovium. Note that the importance of these candidate pathways in vivo remains to be established. See text for details and references. bFGF, basic fibroblast growth factor; IFN, interferon; IL, interleukin; MCP, monocyte chemoattractant protein; M-CSF, macrophage colony-stimulating factor; MIP, macrophage inflammatory protein; PDGF, platelet-derived growth factor; PMN, polymorphonuclear cell; RANK-L, receptor activator of NF-κB ligand; TNF, tumor necrosis factor. (Graphic design by Steve Moskowitz.)