Koch A E, Halloran M M, Haskell C J, Shah M R, Polverini P J
Department of Medicine, Northwestern University Medical School, Chicago, Illinois 60611, USA.
Nature. 1995 Aug 10;376(6540):517-9. doi: 10.1038/376517a0.
Endothelial adhesion molecules facilitate the entry of leukocytes into inflamed tissues. This in turn promotes neovascularization, a process central to the progression of rheumatoid arthritis, tumor growth and wound repair. Here we test the hypothesis that soluble endothelial adhesion molecules promote angiogenesis. Human recombinant soluble E-selectin and soluble vascular cell adhesion molecule-1 induced chemotaxis of human endothelial cells in vitro and were angiogenic in rat cornea. Soluble E-selectin acted on endothelial cells in part through a sialyl Lewis-X-dependent mechanism, while soluble vascular cell adhesion molecule-1 acted on endothelial cells in part through a very late antigen (VLA)-4 dependent mechanism. The chemotactic activity of rheumatoid synovial fluid for endothelial cells, and also its angiogenic activity, were blocked by antibodies to either soluble E-selectin or soluble vascular cell adhesion molecule-1. These results suggest a novel function for soluble endothelial adhesion molecules as mediators of angiogenesis.
内皮黏附分子促进白细胞进入炎症组织。这反过来又促进了新血管形成，这是类风湿性关节炎、肿瘤生长和伤口修复进程中的核心过程。在此，我们检验可溶性内皮黏附分子促进血管生成这一假说。人重组可溶性E选择素和可溶性血管细胞黏附分子-1在体外诱导人内皮细胞趋化，并在大鼠角膜中具有血管生成作用。可溶性E选择素部分通过唾液酸化路易斯-X依赖性机制作用于内皮细胞，而可溶性血管细胞黏附分子-1部分通过极晚期抗原（VLA）-4依赖性机制作用于内皮细胞。类风湿滑膜液对内皮细胞的趋化活性及其血管生成活性，均可被抗可溶性E选择素或抗可溶性血管细胞黏附分子-1抗体阻断。这些结果提示可溶性内皮黏附分子作为血管生成介质的新功能。
