Permissive role of nitric oxide in endothelin-induced migration of endothelial cells.
Endothelin (ET) synthesis is enhanced at sites of ischemia or in injured vessels. The purpose of this study was to explore the possibility of autocrine stimulation of endothelial cell migration by members of the endothelin family. Experiments with microvascular endothelial cell transmigration in a Boyden chemotactic apparatus showed that endothelins 1 and 3, as well as a selective agonist of ETB receptor IRL-1620, equipotently stimulated migration. Endothelial cell migration was unaffected by the blockade of ETA receptor, but it was inhibited by ETB receptor antagonism. Based on our previous demonstration of signaling from the occupied ETB receptor to constitutive nitric oxide (NO) synthase (Tsukahara, H., Ende, H., Magazine, H. I., Bahou, W. F., and Goligorsky, M. S. (1994) J. Biol. Chem. 269, 21778-21785), we next examined the contribution of ET-stimulated NO production to endothelial cell migration. In three independent cellular systems, 1) migration and wound healing by microvascular endothelial cells, 2) wound healing by Chinese hamster ovary cells stably expressing ETB receptor with or without endothelial NO synthase, and 3) application of antisense oligodeoxynucleotides targeting endothelial NO synthase in human umbilical vein endothelial cells, an absolute requirement for the functional NO synthase in cell migration has been demonstrated. These findings establish the permissive role of NO synthesis in endothelin-stimulated migration of endothelial cells.
Noiri
E
E
Department of Medicine, State University of New York, Stony Brook, New York 11794-8152, USA.
Hu
Y
Y
Bahou
W F
WF
Keese
C R
CR
Giaever
I
I
Goligorsky
M S
MS
D000818:Animals; D016466:CHO Cells; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D006224:Cricetinae; D016232:Endothelins / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology*; D006801:Humans; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000235:genetics; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000502:physiology; D011994:Recombinant Proteins / Q000378:metabolism; D014945:Wound Healing
D016232:Endothelins; D016376:Oligonucleotides, Antisense; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D011994:Recombinant Proteins; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase