alpha-Thrombin increases cytosolic calcium and induces human airway smooth muscle cell proliferation.
alpha-Thrombin increases cytosolic calcium and induces human airway smooth muscle cell proliferation.
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α-凝血酶增加胞质钙并诱导人气道平滑肌细胞增殖。
DOI：
10.1165/ajrcmb.13.2.7626288
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Murray,RK
中科院分区：
文献类型：
--
作者：
PanettieriJr,RA;Hall,IP;Maki,CS;Murray,RK
在包括哮喘在内的多种疾病中，炎症引起微血管渗漏并激活凝血酶。除了将纤维蛋白原切割成纤维蛋白外，凝血酶可能还有其他重要的细胞作用。由于气道炎症和血管通透性是气道高反应性的重要决定因素，我们研究了凝血酶对气道平滑肌的影响。利用培养的人气道平滑肌细胞，我们研究了α -凝血酶是否能引起钙反应、磷酸肌肽转换或细胞增殖。我们已经证明，α -凝血酶确实以剂量和时间依赖的方式增加了胞质钙和磷酸肌肽的水解，这种水解可能被水蛭素预处理细胞所抑制。此外，我们已经证明凝血酶刺激气道平滑肌细胞增殖。相比之下，缓激肽虽然能引起细胞质钙和磷酸肌肽周转的增加，但却不能刺激气道平滑肌细胞的生长。我们得出结论，凝血酶有效地增加细胞质钙，诱导PI水解，此外，还能够刺激气道平滑肌细胞的生长。然而，缓激肽缺乏对细胞生长的影响，这表明单纯增加钙和PI的周转不会诱导气道平滑肌细胞增殖。我们认为α -凝血酶可能在气道阻力增加的发病机制以及慢性哮喘导致的结构变化中起重要作用。
In a variety of diseases including asthma, inflammation causes microvascular leakage and activates thrombin. In addition to cleaving fibrinogen to fibrin, thrombin may have other important cellular effects. Because airway inflammation and vascular permeability are important determinants of airway hyperreactivity, we have studied the effects of thrombin on airway smooth muscle. Using cultured human airway smooth muscle cells, we have examined whether alpha-thrombin can evoke calcium responses, phosphoinositide turnover, or cell proliferation. We have demonstrated that alpha-thrombin does increase cytosolic calcium and phosphoinositide hydrolysis in a dose- and time-dependent manner that may be inhibited by pretreating cells with r-hirudin. In addition, we have shown that thrombin stimulates airway smooth muscle cell proliferation. By contrast, bradykinin, which evoked comparable increases in cytosolic calcium and phosphoinositide turnover, did not stimulate airway smooth muscle cell growth. We conclude that thrombin effectively increases cytosolic calcium and induces PI hydrolysis and, in addition, is capable of stimulating airway smooth muscle cell growth. However, the lack of an effect of bradykinin on cell growth suggests that increases in calcium and PI turnover alone will not induce airway smooth muscle cell proliferation. We suggest that alpha-thrombin may be important in the pathogenesis of both increased airway resistance as well as the structural changes seen as a consequence of chronic asthma.