SUBSTANCE-P INDUCES HISTAMINE-RELEASE FROM HUMAN PULMONARY MAST-CELLS

Substance P elicits histamine release from human skin and rodent mast cells. Since neuropeptide-mediated reflexes may be important in asthma , we examined the ability of substance P to stimulate human mast cells obtained at bronchoalveolar lavage (BAL). BAL samples were obtained a t routine bronchoscopy from 35 non-preselected patients. Histamine rel ease experiments were performed in a standard manner using substance P and the calcium ionophore A23187. Both substance P (50 mu M) and A231 87 caused histamine release (median 26.7%, range 6.2-62.8% and 32.1%, 7.7-56.8% respectively) which was significantly greater (P < 0.0001) t han the spontaneous release (median 15.6%, range 4.1-33.4%), i.e. that in the absence of any stimulus. Substance P induced histamine release was via an energy dependent process and was blocked by preincubation with antimycin A. A significant correlation was observed between subst ance P induced release and spontaneous release but was not observed wi th A23187 induced release. Mast cell counts correlated significantly w ith substance P induced release but not with spontaneous or A23187 ind uced release. The substance P induced histamine secretion was elicited at similar concentrations to those used with rodent and human skin ma st cells. Asthma is associated with increased numbers of mast cells wh ich have both increased spontaneous and stimulated secretory responses . Thus, in vivo, the bronchoconstrictor action of substance P may in p art result from activation of mast cells in the bronchial lumen.