Hauser I A, Setter E, Bell L, Madri J A
Department of Pathology, Yale University School of Medicine, New Haven, CT 06510.
Am J Pathol. 1993 Jul;143(1):173-80.
A blood vessel's response to denudation injury will determine its final luminal diameter as well as its function. The synthesis, deposition, and remodeling of extracellular matrix components and migration by vascular endothelial cells are major factors in determining luminal diameter, cellular proliferative and migratory responses, and mononuclear cell adhesion at sites of injury. Previously, we have shown that after in vivo and in vitro denudation injury, endothelial cell migration is dramatically influenced by the amount of fibronectin synthesized and deposited by the responding endothelial cell population. The aim of this study was to elucidate the roles of fibronectin in modulating mononuclear cell adhesion to the endothelial cell population during in vitro migration. In this report we demonstrate that U937 cell binding to the migrating fronts of endothelial cell monolayers is modulated by the amount of fibronectin synthesized and deposited by the endothelial cells. Agents which increase fibronectin deposition, such as transforming growth factor-beta 1, elicit greater U937 cell adhesion. Manipulations that decrease fibronectin deposition, such as transfection and overexpression of pp60c-src proto-oncogene in endothelial cells, reduce U937 cell adhesion. These results suggest that changes in endothelial cell extracellular matrix synthesis and deposition modulate, in part, the adhesive properties of the vessel wall after injury. In turn, the intensity and duration of mononuclear cell adhesion at sites of vessel wall injury determines, in part, the vessel wall response.
血管对剥脱性损伤的反应将决定其最终的管腔直径及其功能。细胞外基质成分的合成、沉积和重塑以及血管内皮细胞的迁移是决定管腔直径、细胞增殖和迁移反应以及损伤部位单核细胞黏附的主要因素。此前，我们已经表明，在体内和体外剥脱性损伤后，内皮细胞迁移受到反应性内皮细胞群体合成和沉积的纤连蛋白量的显著影响。本研究的目的是阐明纤连蛋白在体外迁移过程中调节单核细胞与内皮细胞群体黏附的作用。在本报告中，我们证明U937细胞与内皮细胞单层迁移前沿的结合受到内皮细胞合成和沉积的纤连蛋白量的调节。增加纤连蛋白沉积的因子，如转化生长因子-β1，会引发更强的U937细胞黏附。减少纤连蛋白沉积的操作，如在内皮细胞中转染和过表达pp60c-src原癌基因，会降低U937细胞黏附。这些结果表明，内皮细胞细胞外基质合成和沉积的变化部分调节了损伤后血管壁的黏附特性。反过来，血管壁损伤部位单核细胞黏附的强度和持续时间部分决定了血管壁的反应。
