DISPERSED HUMAN-LUNG MAST-CELLS - PHARMACOLOGIC ASPECTS AND COMPARISON WITH HUMAN-LUNG TISSUE FRAGMENTS

Publisher Website
Google Scholar
Abstract
To study the histamine release and pharmacologic characteristics of dispersed human lung mast cells, particularly in comparison with parenchymal tissue fragments, dispersed human lung mast cells were prepared by enzymatic treatment (yield, 0.5-2 .times. 106 mast cells/g tissue). Purity was 1-8% (mean, 3.6 .+-. 0.7%), and histamine content varied from 2-6 pg/cell (mean, 3.6 .+-. 0.5 pg/cell). Release, studied using anti-IgE as the stimulus, was relatively rapid, being essentially complete within 15 min when high concentrations of anti-IgE (.gtoreq. 0.3 .mu.g/ml) were used, and was not enhanced by phosphatidyl serine. The concentration of drug required to inhibit histamine release by 50% in dispersed cells for a series of pharmacologic agents, including the .beta.-adrenergic agent fenoterol, prostaglandin E2 and the phosphodiesterase inhibitor isobutylmethylxanthine, were 0.1-1, 50 and 0.5 mM, respectively; similar results were obtained in simultaneous experiments performed using tissue fragments. Adenosine enhanced release (19 .+-. 3.4%) at low concentrations (10 .mu.M) and inhibited release (61 .+-. 5.1%) at high concentrations (1 mM). The H2 agonist, dimaprit (10-5-10-7 M) and prostaglandin D2 (10-4-10-6 M) had no effect on histamine release; deuterium oxide potentiated histamine release. This study quantitates the pharmacologic effects of several agents on anti-IgE-mediated histamine release from dispersed human lung mast cells and has further suggested that the dispersed cell system is similar to the standard chopped lung system in dose-response relationships, kinetics and pharmacologic modulation. Apparently, enzymatic treatment of the cells does not affect the release characteristics or functional capacity of several different receptors. This preparation appears suitable as an in vtro human model of mediator release that can be used for the evaluation of pharmacologic agents and for further mast cell purification.