Angiogenesis mediated by soluble forms of E-selectin and vascular cell adhesion molecule-1.
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.
Koch
A E
AE
Department of Medicine, Northwestern University Medical School, Chicago, Illinois 60611, USA.
Halloran
M M
MM
Haskell
C J
CJ
Shah
M R
MR
Polverini
P J
PJ
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000378:metabolism; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism / Q000502:physiology*; D002633:Chemotaxis; D003315:Cornea / Q000166:cytology; D019040:E-Selectin; D004730:Endothelium, Vascular / Q000502:physiology; D006801:Humans; D016256:Lewis X Antigen / Q000502:physiology; D009389:Neovascularization, Pathologic / Q000150:complications / Q000209:etiology* / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins; D012995:Solubility; D013582:Synovial Fluid / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1
D015815:Cell Adhesion Molecules; D019040:E-Selectin; D016256:Lewis X Antigen; D011994:Recombinant Proteins; D019010:Vascular Cell Adhesion Molecule-1