HUMAN HEART MAST-CELLS - A DEFINITIVE CASE OF MAST-CELL HETEROGENEITY

Mast cells and their chemical mediators play a role in cardiac and systemic anaphilaxis. Perivascular and cardiac mast cells have been implicated in the pathogenesis of coronary artery spasm, atherosclerosis, myocardial ischemia, and cardiomyopathy. Despite this, nothing is known about the immunological and biochemical characteristics of the human heart mast cell (HHMC). We have isolated and partially purified HHMC and compared them with mast cells isolated from lung (HLMC) and skin (HSMC) tissues. Cross-linking of the high-affinity receptor for IgE (Fc(epsilon)RI) by a polyclonal anti-Fc(epsilon) antibody caused the release of preformed (histamine and tryptase and de novo synthesized mediators [peptide leukotriene C-4 (LTC(4)) and prostaglandin D-2 (PGD(2))]. The tryptase content of HHMC (19.4+/-1.5 mu g/10(6) cells) was lower than HSMC (33.4+/-2.5 mu g/10(6) cells) and higher than HLMC (10.6+/-1.9 mu g/10(6) cells). Maximal stimulation of HHMC with anti-IgE led to the release of LTC(4) (17.5+/-5.1 ng/10(6) mast cells) and PGD(2) (17.8+/-5.0 ng/10(6) mast cells, whereas HSMC synthesized more PGD(2) (65.0+/-6.8 ng/10(6) mast cells) and much less LTC(4) (<5 ng/10(6) cells). Recombinant human C5a anaphylatoxin and protamine induced histamine release from HHMC and HSMC, but not from HLMC, Substance P and morphine selectively induced the release of histamine from HSMC, but not from HHMC and HLMC. Compound 48/80 caused histamine release from HSMC and HHMC, but not from HLMC. The pattern of mediators synthesized and the responsiveness of HHMC to different secretagogues appear unique providing strong evidence of human mast cell heterogeneity.