Garat C, Kheradmand F, Albertine K H, Folkesson H G, Matthay M A
Cardiovascular Research Institute, University of California, San Francisco 94143-0130, USA.
Am J Physiol. 1996 Nov;271(5 Pt 1):L844-53. doi: 10.1152/ajplung.1996.271.5.L844.
Adhesive interactions between cells and extracellular matrix proteins are important in cell attachment, migration, and proliferation. The present work defines the role of fibronectin (soluble and insoluble) compared with type I and type IV collagen on in vitro alveolar epithelial wound healing. Repeated video microscopy experiments demonstrated that the half-time of wound closure was decreased in the presence of soluble fibronectin (6.6 +/- 2.1 vs. 17.4 +/- 0.8 h in serum-free medium, P < 0.05). Video microscopy, electron microscopy, and vinculin distribution demonstrated the contribution of two main events during the repair process: the migration of epithelial cell sheets and the spreading of the cells. During the wound healing, the internuclear distance between two adjacent cells at the migrating edge of the wound was significantly increased 10 h after wounding in the presence of soluble fibronectin (67 +/- 3.0 vs. 45 +/- 1.5 microns in serum-free medium, P < 0.05), indicating that cell spreading is involved as part of the mechanism for wound closure. Compared with type I and type IV collagen, insoluble fibronectin was the most potent stimulus for alveolar type II cell motility and wound healing in the absence of other serum factors. These results demonstrate that alveolar epithelial wound healing can be modulated in vitro by the composition of the extracellular matrix, an effect that may be mediated by changes in cell shape.
细胞与细胞外基质蛋白之间的黏附相互作用在细胞附着、迁移和增殖过程中起着重要作用。本研究确定了与I型和IV型胶原相比，纤连蛋白（可溶性和不溶性）在体外肺泡上皮伤口愈合中的作用。反复的视频显微镜实验表明，在可溶性纤连蛋白存在的情况下，伤口闭合的半衰期缩短（无血清培养基中分别为6.6±2.1小时和17.4±0.8小时，P<0.05）。视频显微镜、电子显微镜和纽蛋白分布显示了修复过程中两个主要事件的作用：上皮细胞片层的迁移和细胞的铺展。在伤口愈合过程中，伤口迁移边缘两个相邻细胞的核间距在受伤10小时后，在可溶性纤连蛋白存在的情况下显著增加（无血清培养基中分别为67±3.0微米和45±1.5微米，P<0.05），表明细胞铺展是伤口闭合机制的一部分。与I型和IV型胶原相比，在没有其他血清因子的情况下，不溶性纤连蛋白是肺泡II型细胞运动和伤口愈合的最有效刺激物。这些结果表明，肺泡上皮伤口愈合在体外可通过细胞外基质的组成进行调节，这种作用可能由细胞形状的变化介导。
