Heaney L G, Cross L J, Stanford C F, Ennis M
Department of Clinical Biochemistry, Queen's University of Belfast, UK.
Clin Exp Allergy. 1995 Feb;25(2):179-86. doi: 10.1111/j.1365-2222.1995.tb01024.x.
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 at routine bronchoscopy from 35 non-preselected patients. Histamine release experiments were performed in a standard manner using substance P and the calcium ionophore A23187. Both substance P (50 microM) and A23187 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) than 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 substance P induced release and spontaneous release but was not observed with A23187 induced release. Mast cell counts correlated significantly with substance P induced release but not with spontaneous or A23187 induced release. The substance P induced histamine secretion was elicited at similar concentrations to those used with rodent and human skin mast cells. Asthma is associated with increased numbers of mast cells which have both increased spontaneous and stimulated secretory responses. Thus, in vivo, the bronchoconstrictor action of substance P may in part result from activation of mast cells in the bronchial lumen.
P物质可引起人皮肤和啮齿动物肥大细胞释放组胺。由于神经肽介导的反射在哮喘中可能很重要,我们研究了P物质刺激通过支气管肺泡灌洗(BAL)获得的人肥大细胞的能力。在常规支气管镜检查时从35例未预先选择的患者中获取BAL样本。使用P物质和钙离子载体A23187以标准方式进行组胺释放实验。P物质(50微摩尔)和A23187均引起组胺释放(中位数分别为26.7%,范围6.2 - 62.8%和32.1%,7.7 - 56.8%),这显著高于(P < 0.0001)自发释放(中位数15.6%,范围4.1 - 33.4%),即无任何刺激时的释放。P物质诱导的组胺释放是通过能量依赖过程,并且可被与抗霉素A预孵育所阻断。观察到P物质诱导的释放与自发释放之间存在显著相关性,但A23187诱导的释放未观察到这种相关性。肥大细胞计数与P物质诱导的释放显著相关,但与自发或A23187诱导的释放无关。P物质诱导的组胺分泌在与用于啮齿动物和人皮肤肥大细胞的相似浓度下引发。哮喘与肥大细胞数量增加有关,这些肥大细胞的自发和刺激分泌反应均增强。因此,在体内,P物质的支气管收缩作用可能部分源于支气管腔内肥大细胞的激活。