Substance P activates the release of histamine from human skin mast cells through a pertussis toxin-sensitive and protein kinase C-dependent mechanism

被引:63
作者
Columbo, M
Horowitz, EM
KageySobotka, A
Lichtenstein, LM
机构
[1] Div. of Allerg. and Clin. Immunology, Johns Hopkins Asthma and Allerg. C., Johns Hopkins Univ. Sch. of Medicine, Baltimore, MD 21224
[2] Div. of Allerg. and Clin. Immunology, Johns Hopkins Asthma and Allerg. C., Baltimore, MD 21224
来源
CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY | 1996年 / 81卷 / 01期
关键词
D O I
10.1006/clin.1996.0159
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Using pharmacologic agents, we explored the mechanism by which a potent neuropeptide, substance P, induces the secretion of histamine from human skin mast cells and compared their effects on substance P-induced histamine release to the secretion activated by anti-IgE. Histamine release from human cutaneous mast cells induced by substance P was inhibited by the G(e)-protein inhibitor pertussis toxin that, in turn, did not affect the IgE-mediated secretion. Similarly to anti-IgE, two activators of protein kinase C, tetradecanoylphorbol acetate (TPA) and bryostatin 1, significantly inhibited the substance P-induced response. In contrast, drugs that enhance intracellular levels of cAMP, an inhibitor of protein kinases, genistein, and a protease inhibitor, AEBSF, did not affect substance P-induced histamine secretion, whereas these compounds significantly reduced the response initiated by anti-IgE. Our data demonstrate that substance P activates human cutaneous mast cells by acting on C proteins and protein kinase C. Our results also suggest that the biochemical pathways underlying mast cell activation by substance P and anti-IgE are to a great extent unrelated. (C) 1996 Academic Press, Inc.
引用
收藏
页码:68 / 73
页数:6
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