Brown C, Stenn K S, Falk R J, Woodley D T, O'Keefe E J
Department of Dermatology, Yale University.
J Invest Dermatol. 1991 May;96(5):724-8. doi: 10.1111/1523-1747.ep12470960.
Epibolin, a plasma protein, was initially purified on the basis of its ability to enhance spreading of keratinocytes. It is now known that epibolin is identical to serum spreading factor, S protein, and vitronectin, and the current name for the protein is vitronectin. Studies of vitronectin on cultured keratinocytes showed that it caused spreading and epiboly but not cellular adhesion to the substratum. In studies with other types of cells, vitronectin increased migration of several types of cells in a Boyden chamber. Because some agents that enhance spreading and adhesion, such as collagen and fibronectin, also increase motility, we tested whether vitronectin increased motility of keratinocytes. By photographing and quantitating motility of keratinocytes plated on a bed of colloidal gold particles, we determined that vitronectin increased local movement of keratinocytes in a concentration-dependent fashion, resulting in clearing of gold particles in a circular pattern around the cells, but did not cause the production of tracks found in cultures plated on collagen or fibronectin. The small increases in clearing of the gold particles that occurred in the presence of vitronectin were abolished by antibody to vitronectin. Furthermore, the marked increase in motility produced by type I collagen was significantly reduced when the keratinocytes were treated with vitronectin. Antibody to vitronectin also abrogated the vitronectin-induced reduction in collagen-stimulated motility, confirming that this action was specific for vitronectin. Serum, which contains vitronectin, stimulated motility in a fashion identical to purified vitronectin, but serum lacking vitronectin was inactive. These studies show that vitronectin causes a localized increase in movement associated with spreading resulting in a halo around individual cells, that vitronectin does not enhance directional motility of keratinocytes in this assay but in contrast antagonizes such motility produced by collagen, and that vitronectin is the factor in serum responsible for this effect. The findings with vitronectin and collagen show that these agents stimulate different types of motility. The roles in wound healing of agents stimulating different types of motility are unclear and require further study.
表皮生成素是一种血浆蛋白，最初是根据其增强角质形成细胞铺展的能力而被纯化出来的。现在已知表皮生成素与血清铺展因子、S蛋白和玻连蛋白相同，该蛋白目前的名称是玻连蛋白。对培养的角质形成细胞进行的玻连蛋白研究表明，它能引起细胞铺展和外包，但不会使细胞黏附于基质。在对其他类型细胞的研究中，玻连蛋白增加了博伊登小室中几种类型细胞的迁移。由于一些增强铺展和黏附的因子，如胶原蛋白和纤连蛋白，也能增加细胞运动性，因此我们测试了玻连蛋白是否会增加角质形成细胞的运动性。通过拍摄并定量接种在胶体金颗粒床上的角质形成细胞的运动性，我们确定玻连蛋白以浓度依赖的方式增加角质形成细胞的局部运动，导致细胞周围的金颗粒呈圆形清除，但不会产生接种在胶原蛋白或纤连蛋白上的培养物中发现的轨迹。在有玻连蛋白存在的情况下，金颗粒清除的小幅增加被玻连蛋白抗体消除。此外，当角质形成细胞用玻连蛋白处理时，I型胶原蛋白所产生的显著运动性增加明显降低。玻连蛋白抗体也消除了玻连蛋白诱导的胶原蛋白刺激的运动性降低，证实了这种作用对玻连蛋白具有特异性。含有玻连蛋白的血清以与纯化玻连蛋白相同的方式刺激运动性，但缺乏玻连蛋白的血清则无活性。这些研究表明，玻连蛋白会导致与铺展相关的局部运动增加，从而在单个细胞周围形成光晕；在该实验中，玻连蛋白不会增强角质形成细胞的定向运动性，反而会拮抗胶原蛋白产生的这种运动性；玻连蛋白是血清中产生这种效应的因子。玻连蛋白和胶原蛋白的研究结果表明，这些因子刺激不同类型的运动性。刺激不同类型运动性的因子在伤口愈合中的作用尚不清楚，需要进一步研究。
