Characterization of histamine secretion from mechanically dispersed human lung mast cells: effects of anti-IgE, calcium ionophore A23187, compound 48/80, and basic polypeptides.

Abstract

Abstract Human lung mast cells dispersed by a mechanical method not involving enzymatic digestion have been demonstrated to release a granule-associated preformed mediator, histamine, in a concentration-related manner when incubated with anti-lgE or the calcium ionophore A23187. That this release was noncytotoxic was demonstrated by its total dependence upon functional glycolysis and the presence of extracellular calcium and by the failure to detect concomitant release of the cytoplasmic marker LDH. Maximum histamine release induced by A23187 32.8 ± 4.8% is lower than that observed from rat peritoneal mast cells or human basophils. In individual experiments, a correlation between release induced by anti-lgE and A23187 suggests that, in addition to the degree of immunologic stimulation, an intrinsic donor-determined factor controls cell releasability. In kinetic experiments, the rate of histamine release depended on the degree of stimulation with anti-lgE or A21387 and upon the final maximum histamine release. Anti-lgE-in-duced release was complete in 2 to 5 min, while, with optimal concentrations of A23187, 10 min was required for completion of release. Compound 48/80, in contrast to its effects in rat peritoneal mast cells, produced significant histamine release only at the highest concentration used, 1000 jug/ml. This was probably due to cytotoxicity, since it was independent of glycolysis and extracellular calcium and was accompanied by LDH release. The heterogeneity of histamine-releasing cells both between and within species was further highlighted by the refractory nature of human lung cells to IgE-decapeptide and corticotropin-(1-24)-peptide, which are potent noncytotoxic releasers from rat peritoneal mast cells, and to polyarginine and polylysine, which are also effective secretagogues in human leukocyte basophils. Thus, extreme caution must be exercised in extrapolating results obtained using mast cells from experimental animals to predict the functional characteristics of the human lung mast cell.