Endothelial intercellular adhesion molecule (ICAM)-2 regulates angiogenesis.
Endothelial junctions maintain endothelial integrity and vascular homeostasis. They modulate cell trafficking into tissues, mediate cell-cell contact and regulate endothelial survival and apoptosis. Junctional adhesion molecules such as vascular endothelial (VE)-cadherin and CD31/platelet endothelial cell adhesion molecule (PECAM) mediate contact between adjacent endothelial cells and regulate leukocyte transmigration and angiogenesis. The leukocyte adhesion molecule intercellular adhesion molecule 2 (ICAM-2) is expressed at the endothelial junctions. In this study we demonstrate that endothelial ICAM-2 also mediates angiogenesis. Using ICAM-2-deficient mice and ICAM-2-deficient endothelial cells, we show that the lack of ICAM-2 expression results in impaired angiogenesis both in vitro and in vivo. We show that ICAM-2 supports homophilic interaction, and that this may be involved in tube formation. ICAM-2-deficient cells show defective in vitro migration, as well as increased apoptosis in response to serum deprivation, anti-Fas antibody, or staurosporine. ICAM-2 signaling in human umbilical vein endothelial cells (HUVECs) was found to activate the small guanosine triphosphatase (GTPase) Rac, which is required for endothelial tube formation and migration. These data indicate that ICAM-2 may regulate angiogenesis via several mechanisms including survival, cell migration, and Rac activation. Our findings identify a novel pathway regulating angiogenesis through ICAM-2 and a novel mechanism for Rac activation during angiogenesis.
Huang
Miao-Tzu
MT
Imperial College, BHF Cardiovascular Sciences Unit, Hammersmith Hospital, Du Cane Road, London W12 0NN, United Kingdom.
Mason
Justin C
JC
Birdsey
Graeme M
GM
Amsellem
Valerie
V
Gerwin
Nicole
N
Haskard
Dorian O
DO
Ridley
Anne J
AJ
Randi
Anna M
AM
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D017209:Apoptosis / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D042783:Endothelial Cells / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology*; D020744:rac GTP-Binding Proteins / Q000378:metabolism
D015703:Antigens, CD; D015815:Cell Adhesion Molecules; C480027:ICAM-2 protein, mouse; D020744:rac GTP-Binding Proteins