Integrin α3-subunit expression modulates alveolar epithelial cell monolayer formation
Integrin α3-subunit expression modulates alveolar epithelial cell monolayer formation
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DOI：
10.1152/ajplung.2000.279.1.l183
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发表时间：
2000-07-01
影响因子：
4.9
通讯作者：
Borok, Z
中科院分区：
文献类型：
--
作者：
Lubman, RL;Zhang, XL;Borok, Z
我们研究了α（3）-整联蛋白亚基的表达，大鼠肺泡上皮细胞（AEC）生长在原代培养，以及单克隆抗体的影响，阻断活性对α（3）-整联蛋白亚基AEC单层形成。在培养第1天的AEC中可检测到α（3）-整合素亚基mRNA和蛋白，并随培养时间的延长而增加。在免疫沉淀实验中，α 3和β 1整合素亚基与α 3和β 1亚基特异性抗体共沉淀，这与它们在细胞膜上作为α 3 β 1整合素受体的结合一致。与未处理的AEC相比，从第0天开始用阻断性抗α 3单克隆抗体处理延迟了跨上皮阻力的发展，降低了跨上皮阻力，并在第3天通过扫描电子显微镜观察到单层中的大的亚融合斑块。这些数据表明α（3）-和β（1）-整联蛋白亚基在AEC单层中表达，在那里它们在细胞膜上形成异二聚体α（3）β（1）-整联蛋白受体。阻断α 3-整联蛋白亚基可抑制融合AEC单层的形成。我们的结论是，α（3）-整联蛋白亚基调节AEC单层的形成凭借的α（3）β（1）-整联蛋白受体在AEC粘附的关键作用。
We investigated expression of the alpha(3)-integrin subunit by rat alveolar epithelial cells (AECs) grown in primary culture as well as the effects of monoclonal antibodies with blocking activity against the alpha(3)-integrin subunit on AEC monolayer formation. alpha(3)-Integrin subunit mRNA and protein were detectable in AECs on day 1 and increased with time in culture. alpha(3)- and beta(1)-integrin subunits coprecipitated in immunoprecipitation experiments with alpha(3)- and beta(1)-subunit-specific antibodies, consistent with their association as the alpha(3)beta(1)-integrin receptor at the cell membrane. Treatment with blocking anti-alpha(3) monoclonal antibody from day 0 delayed development of transepithelial resistance, reduced transepithelial resistance through day 5 compared with that in untreated AECs, and resulted in large subconfluent patches in monolayers viewed by scanning electron microscopy on day 3. These data indicate that alpha(3)- and beta(1)-integrin subunits are expressed in AEC monolayers where they form the heterodimeric alpha(3)beta(1)-integrin receptor at the cell membrane. Blockade of the alpha(3)-integrin subunit inhibits formation of confluent AEC monolayers. We conclude that the alpha(3)-integrin subunit modulates formation of AEC monolayers by virtue of the key role of the alpha(3)beta(1)-integrin receptor in AEC adhesion.