周期性应变诱导人肺上皮细胞整联蛋白再分布的研究

Cyclic Strain Induces Reorganization of Integrins in Human Pulmonary Epithelial Cells

为了探讨机械拉伸应变对人肺上皮细胞表面整联蛋白α3 、α5和 β1分布的调控作用 ,建立了体外周期性拉伸应变装置 ,并应用胞外基质蛋白———纤连蛋白 (Fn)、胶原蛋白Ⅳ (ColⅣ )裱衬基底膜 ,激光共聚焦显微镜分析了在应变为 15 % ,频率为 4 0次 /min的拉伸刺激下 ,正常人肺上皮细胞H72 7表面α3 、α5和 β1整联蛋白的再分布 .结果表明 :在人肺上皮细胞H72 7中 ,α3 、α5和 β1整联蛋白是对拉伸应变敏感的膜受体 ,周期性拉伸刺激可诱导其激活 ,使之发生分布的重组 ,并向基底层转移 ,形成局部粘附连接 ,增强了整联蛋白受体与其特异性配体的结合能力 .结果提示 :一个有效的局部粘附连接的形成是受体聚集和配体占据共同启动的一个协调反应 ,该反应可能参与了细胞响应机械应力的起始过程 ,可能进一步通过力 化学信号的耦合或张力整合的形式 。

In order to study the effects of mechanical strain on distribution of integrins in normal human pulmonary epithelial cell line H727, a cyclic strain unit in vitro was set up, and the redistribution of alpha(3), alpha(5), beta(1) integrin in H727 cells subjected to 24 h cyclic strain was analyzed. Human pulmonary epithelial H727 cells seeded on either fibronectin or collagen IV surfaces were subjected to 15% elongation at a frequency of 40 cycles/min. Confocal microcopy revealed that alpha(3), beta(5), beta(1) integrin in H727 cells were concentrated and brighter, and cells created a large fusion of focal adhesion or adhesion plaques after 24 h exposure to strain. Under static condition alpha(3), alpha(5), beta(1) integrin in H727 cells maintained a diffuse pattern with an occasional speckle concentration in some regions. Furthermore alpha(3), alpha(5), beta(1) integrin in H727 cells transferred from the apical layer to the basal layer and created adhesion plaques, and affinity between integrins and extracellular matrices ( ECM) was enhanced. It is concluded that the formation of effective focal contacts is the concerted interaction between receptors recruitment and ligand occupy. This interaction plays an important role in transducing mechanical stimuli into intracellular signals.