![]() ![]() ![]() Mast cells are found principally in mucosae and in connective tissue, generally clustered at epithelial surfaces and around nerves and blood vessels. We review here the functions of mast cells as a prelude to the discussion of the current state of knowledge about the role of mast cells in murine and human inflammatory arthritis. This finding has renewed interest in older histological data documenting prominent mast cell infiltrates in the rheumatoid synovium. Recently, several laboratories have established that mast cells have a critical role in the pathogenesis of synovitis in a murine system with considerable similarity to rheumatoid arthritis (RA). Beyond the acute phase of the immune response, mast cells may participate in the response of tissue to injury by means of mediators that promote angiogenesis and fibrosis. Correspondingly, mice deficient in mast cells have been found to exhibit striking susceptibility to death from certain types of bacterial infection. ![]() Mast cells are capable of phagocytosis, intracellular killing, and antigen presentation. Mast cells express surface receptors for IgG, complement, and specific pathogen-associated molecular patterns. However, research over the past two decades has revealed that the role of mast cells is not limited to IgE-mediated immune responses. Clinical manifestations can range from seasonal allergic rhinitis to life-threatening anaphylaxis. Crosslinking of surface-bound IgE results in the immediate release of granule contents, including histamine, and the more gradual elaboration of other proinflammatory mediators. The mast cell has long been known to mediate important manifestations of allergic disease. Here we review some of the non-allergic functions of mast cells and focus on the potential role of these cells in murine and human inflammatory arthritis. Accumulating within inflamed tissues, mast cells produce cytokines and other mediators that may contribute vitally to ongoing inflammation. Equipped with a diversity of surface receptors and effector capabilities, mast cells are sentinels of the immune system, detecting and delivering a first response to invading bacteria and other insults. This finding highlights the results of more than 20 years of research indicating that mast cells are frequent participants in non-allergic immune responses as well as in allergy. Recent investigations in a murine model have demonstrated that mast cells can have a critical role in the generation of inflammation within the joint. Mast cells are present in limited numbers in normal human synovium, but in rheumatoid arthritis and other inflammatory joint diseases this population can expand to constitute 5% or more of all synovial cells. ![]()
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