Tryptase-stimulated human airway smooth muscle cells induce cytokine synthesis and mast cell chemotaxis
Tryptase-stimulated human airway smooth muscle cells induce cytokine synthesis and mast cell chemotaxis
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DOI：
10.1096/fj.03-0041fje
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发表时间：
2003-09-01
期刊：
影响因子：
4.8
通讯作者：
de Lara, JMT
中科院分区：
文献类型：
--
作者：
Berger, P;Girodet, PO;de Lara, JMT
哮喘患者的气道平滑肌层中肥大细胞数量高于正常人。人气道平滑肌细胞（HASMCs）是各种细胞因子的来源，包括转化生长因子β 1（TGF-β 1），其对肥大细胞具有趋化性。因此，我们已经研究了HASMCs和肥大细胞之间的相互作用的潜力，并调查，特别是，刺激后，HASMCs可以诱导肥大细胞的趋化性，通过生产细胞因子的假设。用肥大细胞主要产物类胰蛋白酶处理的HASMCs上清液对HMC-1肥大细胞系的趋化活性增加。这种效应依赖于类胰蛋白酶的完整催化位点，并且可以由蛋白酶激活受体2的肽激动剂诱导。趋化活性与HASMCs合成TGF-β 1有关，在较小程度上与干细胞因子有关。哮喘患者平滑肌层内肥大细胞的数量与平滑肌表达TGF-β 1密切相关。因此，HASMCs可能能够刺激肥大细胞的积累，而这些细胞又可能刺激HASMCs分泌趋化因子。
Asthmatic patients have higher numbers of mast cells in the smooth muscle layer of airways than normal subjects. Human airway smooth muscle cells (HASMCs) are a source of various cytokines including transforming growth factor beta1 (TGF-beta1), which is chemotactic for mast cells. We have thus examined the potential for interaction between HASMCs and mast cells and have investigated, in particular, the hypothesis that after stimulation, HASMCs can induce mast cell chemotaxis through the production of cytokines. Supernatants of HASMCs treated with the major mast cell product tryptase had increased chemotactic activity for the HMC-1 mast cell line. The effect depended on an intact catalytic site for tryptase and could be induced by a peptide agonist for protease activated receptor 2. Chemotactic activity was related to the synthesis of TGF-beta1 by HASMCs and, to a lesser extent, to stem cell factor. The number of mast cells within the smooth muscle layer of asthmatic patients was closely related to TGF-beta1 expression by smooth muscle. HASMCs may thus be able to stimulate the accumulation of mast cells, and these cells may, in turn, stimulate the secretion of chemotactic factors by HASMCs.