Angiogenesis mediated by soluble forms of E-selectin and vascular cell adhesion molecule-1

• Published in: Nature (London) Vol. 376; no. 6540; pp. 517 - 519
• Main Authors: Koch, Alisa E, Halloran, Margaret M, Haskell, Catherine J, Shah, Manisha R, Polverini, Peter J
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 10.08.1995; Nature Publishing Group
• Subjects: Animals; Arthritis, Rheumatoid - complications; Arthritis, Rheumatoid - metabolism; Biochemistry; Biological and medical sciences; Cell Adhesion; Cell Adhesion Molecules - metabolism; Cell Adhesion Molecules - physiology; Cell differentiation, maturation, development, hematopoiesis; Cell physiology; Chemotaxis; Cornea - cytology; E-Selectin; Endothelium, Vascular - physiology; Fundamental and applied biological sciences. Psychology; Humans; Lewis X Antigen - physiology; Molecular and cellular biology; Neovascularization, Pathologic - complications; Neovascularization, Pathologic - etiology; Neovascularization, Pathologic - metabolism; Rats; Recombinant Proteins; Solubility; Synovial Fluid - metabolism; Vascular Cell Adhesion Molecule-1; Human; ascular cell adhesion molecule 1; Endothelial cell; Rat; E Selectin; Rodentia; Cell adhesion molecule; Chemotaxis; In vitro; Biological activity; Endothelium; Angiogenesis; Vertebrata; Mammalia; Blood vessel; Circulatory system
• ISSN: 0028-0836; 1476-4687
• 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.