Lung alveolar epithelial cell migration in vitro: Modulators and regulation processes

Lung alveolar epithelial cell migration in vitro: Modulators and regulation processes
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DOI:
10.1152/ajplung.1996.270.3.l311
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发表时间:
1996-03-01
影响因子:
4.9
通讯作者:
Lane, D
Lane, D
中科院分区:
医学2区
文献类型:
--
作者:
Lesur, O;Arsalane, K;Lane, D

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急性肺损伤后,改变的细支气管肺泡上皮必须迅速修复,以恢复肺功能。在再上皮化过程中,II型细胞最初似乎迁移并扩散到重塑的基质上;然后出现第二个增殖期。假设1)II型细胞可以在体外形成运动,其由生长因子、促炎细胞因子和底物粘附分子调节,2)II型细胞的迁移和增殖可以作为独特的过程发生。使用大鼠II型肺细胞的短期培养物阐述了趋化性测定。表皮生长因子(EGF)、转化生长因子-α、层粘连蛋白、纤连蛋白被发现是II型细胞的主要吸引剂,在细胞迁移中分别增加了8.5倍、10.5倍、8倍和7倍(与对照相比P < 0.05)。层粘连蛋白诱导梯度依赖性和随机细胞迁移。加入层粘连蛋白和EGF在促进细胞迁移方面具有协同作用(与对照相比增加30倍,P < 0.05)。干扰素-γ和白细胞介素-6抑制EGF诱导的II型细胞迁移,而肿瘤坏死因子-α和白细胞介素-1 β作为II型细胞迁移的引物(与对照组相比增加1.5倍,P < 0.05)。II型细胞不需要处于增殖期才能表现出运动性。关于II型细胞迁移的调节过程的新见解与我们对急性肺损伤后上皮修复过程中发生的早期事件的理解特别相关。
After acute lung injury, altered bronchioloalveolar epithelia must be repaired quickly in order to restore lung function. During reepithelialization, type II cells initially appear to migrate and spread over a remodeled matrix; then a secondary proliferative phase occurs. It was hypothesized that 1) type II cells can develop locomotion in vitro that is modulated by growth factors, proinflammatory cytokines, and substrate adhesion molecules and 2) migration and proliferation of type II cells can occur as distinctive processes. Chemotaxis assays were elaborated using shortterm cultures of rat type II pneumocytes. Epidermal growth factor (EGF), transforming growth factor-alpha, laminin, fibronectin were found to be the main attractants for type II cells with respective increases of similar to 8.5-, 10.5-, 8-, and 7-fold in cell migration (P < 0.05 vs. control). Laminin induced gradient-dependent and random cell migration. Addition of laminin with EGF had a synergistic effect in promoting cell migration (similar to 30-fold increase over control, P < 0.05). Interferon-gamma and interleukin-6 inhibited EGF-induced type II cell migration, whereas tumor necrosis factor-ct and interleukin-1 beta acted as primers for type II cell migration (similar to 1.5-fold increase over control, P < 0.05). Type II cells did not need to be in a proliferative phase in order to exhibit motility. New insights regarding the regulatory processes for type II cell migration are especially relevant in our understanding of early events occurring during epithelial repair after acute lung injury.