Kim H J, Henke C A, Savik S K, Ingbar D H
Department of Medicine, University of Minnesota Medical School, Minneapolis 55455, USA.
Am J Physiol. 1997 Jul;273(1 Pt 1):L134-41. doi: 10.1152/ajplung.1997.273.1.L134.
Acute lung injury leads to type I alveolar epithelial cell (AEC) death, denudation of the alveolar basement membrane, and formation of an alveolar provisional matrix from fibronectin, fibrinogen, and type I collagen. The provisional matrix provides a scaffold for alveolar repair. To restore normal lung architecture, surviving type II AECs must reepithelialize denuded alveoli. We examined whether AECs migrate on provisional matrix proteins and whether integrins mediate this migration using a Boyden chemotaxis chamber. Cultured AECs migrated on fibronectin-coated filters by haptotaxis (defined as movement on a solid-phase substrate) more than one type I collagen-coated filters, and they did not migrate on fibrinogen-coated filters. Soluble fibronectin augmented migration on type I collagen-coated filters, but not on fibronectin-coated filters. Anti-alpha v beta 3-integrin monoclonal antibody (MAb) inhibited migration on substrate-bound fibronectin by 62-77%, whereas anti-beta 1-integrin MAb inhibited migration by 48%. Anti-alpha 2-integrin MAb almost completely inhibited migration on substrate-bound type I collagen, but not on fibronectin. The novel findings in this study are as follows: 1) AECs migrate by haptotaxis more effectively on substrate-bound fibronectin than on type I collagen; 2) alpha v beta 3- and beta 1-integrins partially mediate AEC haptotaxis on fibronectin; and 3) the alpha 2 beta 1-integrin mediates AEC migration on type I collagen. These results support the importance of type II cell migration on provisional matrix proteins during repair of lung injury.
急性肺损伤导致I型肺泡上皮细胞（AEC）死亡、肺泡基底膜剥脱，并由纤连蛋白、纤维蛋白原和I型胶原形成肺泡临时基质。该临时基质为肺泡修复提供支架。为恢复正常肺结构，存活的II型AEC必须重新上皮化剥脱的肺泡。我们使用Boyden趋化室研究了AEC是否在临时基质蛋白上迁移以及整合素是否介导这种迁移。培养的AEC通过趋触性（定义为在固相基质上的移动）在纤连蛋白包被的滤膜上迁移的程度超过I型胶原包被的滤膜，且它们不在纤维蛋白原包被的滤膜上迁移。可溶性纤连蛋白增强了在I型胶原包被滤膜上的迁移，但在纤连蛋白包被滤膜上无此作用。抗αvβ3整合素单克隆抗体（MAb）抑制在底物结合的纤连蛋白上的迁移达62% - 77%，而抗β1整合素MAb抑制迁移达48%。抗α2整合素MAb几乎完全抑制在底物结合的I型胶原上的迁移，但对纤连蛋白无此作用。本研究的新发现如下：1）AEC通过趋触性在底物结合的纤连蛋白上比在I型胶原上更有效地迁移；2）αvβ3和β1整合素部分介导AEC在纤连蛋白上的趋触性；3）α2β1整合素介导AEC在I型胶原上的迁移。这些结果支持了II型细胞在肺损伤修复过程中在临时基质蛋白上迁移的重要性。
