HUMAN SYNOVIAL MAST-CELLS .1. ULTRASTRUCTURAL IN-SITU AND IN-VITRO IMMUNOLOGICAL CHARACTERIZATION

Objective. To examine the ultrastructure of human synovial mast cells in situ, to identify immunologic and nonimmunologic stimuli that activ ate 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 immuno-electron mic roscopy localization of tryptase and chymase, Isolated synovial mast c ells were analyzed biochemically, immunologically, and functionally in vitro and compared with cells from human lung, heart, and skin. Resul ts. 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 evide nce of degranulation, Immunoelectron microscopy demonstrated the subce llular localization of tryptase and chymase over granules of >90% of t he mast cells, which were of the MC(TC) subtype, Isolated synovial mas t cells released histamine in response to immunologic (anti-IgE and an ti-Fc epsilon receptor I [anti-Fc epsilon RI]) and nonimmunologic (sub stance 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 o f 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 Fc epsilon RI. Cross-l inking of IgE with anti-IgE on synovial mast cells induced de novo syn thesis of prostaglandin D-2 (mean +/- SEM 87.5 +/- 4.9 ng/10(6) cells) and of leukotriene C-4 (57.6 +/- 17.8 ng/10(6) cells). Conclusion. Ma st cells ultrastructurally characterized in situ in synovial tissue we re seen to differ from mast cells previously isolated from other human tissues, This raises the possibility that the local microenviroment i nfluences their phenotype, Isolation of mast cells from human synovia can be useful for studying their role and their mediators in patients with arthritis.