Johnson P R, Ammit A J, Carlin S M, Armour C L, Caughey G H, Black J L
Dept of Pharmacology, University of Sydney NSW, Australia.
Eur Respir J. 1997 Jan;10(1):38-43. doi: 10.1183/09031936.97.10010038.
The mast cell plays a pivotal role in the early asthmatic response via release of mediators, which directly influence airway smooth muscle tone. Canine mast cell tryptase has been reported to potentiate the contractile response of canine isolated airways to histamine. The aim of this study was to investigate whether human mast cell tryptase potentiated contractile responses in human isolated bronchi. The effect of tryptase differed according to the sensitization status of the bronchi. In lung tissue from sensitized patients (those whose bronchial tissue contracted in response to the application of any of four common antigens) 90 ng.mL-1 of human purified lung tryptase markedly potentiated the contractile response to histamine. The maximal response as a percentage of maximal contraction to acetylcholine was 80 +/- 8% in control tissues and 119 +/- 6% in tryptase treated tissues (n = 4; p < 0.05). Tryptase, at a dose of 200 ng.mL-1, also potentiated responses but to a lesser degree, 100 +/- 5% (n = 4; p < 0.05). In nonsensitized bronchi, neither 90 nor 200 ng.mL-1 tryptase had any significant effect on histamine responses. The increased response in the presence of tryptase in sensitized tissue was inhibited by the calcium voltage-dependent channel antagonist, verapamil (10(-6) M). We have shown, for the first time, that human mast cell tryptase potentiates contraction in sensitized bronchi via a calcium-related mechanism. These findings provide a link between a mast cell derived product and in vitro human airway hyperresponsiveness.
肥大细胞通过释放介质在哮喘早期反应中起关键作用，这些介质直接影响气道平滑肌张力。据报道，犬类肥大细胞胰蛋白酶可增强犬类离体气道对组胺的收缩反应。本研究的目的是调查人肥大细胞胰蛋白酶是否能增强人离体支气管的收缩反应。胰蛋白酶的作用因支气管的致敏状态而异。在致敏患者的肺组织（即支气管组织对四种常见抗原中的任何一种施加均有收缩反应的患者）中，90 ng/mL的人纯化肺胰蛋白酶显著增强了对组胺的收缩反应。对照组织中对组胺最大收缩反应的百分比为80±8%，而胰蛋白酶处理的组织中为119±6%（n = 4；p < 0.05）。200 ng/mL剂量的胰蛋白酶也能增强反应，但程度较小，为100±5%（n = 4；p < 0.05）。在未致敏的支气管中，90 ng/mL和200 ng/mL的胰蛋白酶对组胺反应均无显著影响。致敏组织中存在胰蛋白酶时反应的增强被钙电压依赖性通道拮抗剂维拉帕米（10⁻⁶ M）抑制。我们首次表明，人肥大细胞胰蛋白酶通过钙相关机制增强致敏支气管的收缩。这些发现提供了一种肥大细胞衍生产物与体外人气道高反应性之间的联系。
