Objective. To examine the ultrastructure of human synovial mast cells in situ, to identify immunologic and nonimmunologic stimuli that activate these cells in vitro, and to quantify a number of preformed and de novo-synthesized mediators. Methods. We conducted an ultrastructural study of synovial mast cells in situ and performed immunoelectron microscopy localization of tryptase and chymase. Isolated synovial mast cells were analyzed biochemically, immunologically, and functionally in vitro and compared with cells from human lung, heart, and skin. Results. Ultrastructural study of synovial tissue revealed mast cells with homogeneously dense, scrolled, crystal, and mixed granules, and lipid bodies in the cytoplasm. A small percentage of mast cells showed evidence of degranulalion. Immunoelectron microscopy demonstrated the subcellular localization of tryptase and chymase over granules of >90% of the mast cells, which were of the MC(TC) subtype. Isolated synovial mast cells released histamine in response to immunologic (anti-IgE and anti-Fcε receptor I [anti-FcεRII) and nonimmunologic (substance P, recombinant human stem cell factor, and 48/80) stimuli, but did not respond to recombinant human C5a in vitro. Synovial mast cells differed from those isolated from other human tissues, in a variety of immunologic and biochemical features. There was a linear correlation between the percentage of histamine secretion and tryptase release (r = 0.79, P <0.001) induced by cross-linking of FcεRI. Cross-linking of IgE with anti-IgE on synovial mast cells induced de novo synthesis of prostaglandin D2 (mean ± SEM 87.5 ± 4.9 ng/106 cells) and of leukotriene C4 (57.6 ± 17.8 ng/106 cells). Conclusion. Mast cells ultrastructurally characterized in situ in synovial tissue were seen to differ from mast cells previously isolated from other human tissues. This raises the possibility that the local microenviroment influences their phenotype. Isolation of mast cells from human synovia can be useful for studying their rule and their mediators in patients with arthritis.
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