Differential roles of ICAM-1 and E-selectin in polymorphonuclear leukocyte-induced angiogenesis.
Ets-1, which stimulates metalloproteinase gene transcription, has a key role in angiogenesis. We first examined whether activated polymorphonuclear leukocytes (PMNs) enhanced angiogenesis through the induction of Ets-1. Addition of activated PMNs to endothelial cells stimulated both in vitro angiogenesis in collagen gel and Ets-1 expression. Both angiogenesis and Ets-1 expression induced by PMNs were reduced by ets-1 antisense oligonucleotide, suggesting that Ets-1 is an important factor in PMN-induced angiogenesis. Although intercellular adhesion molecule (ICAM)-1 and E-selectin are involved in PMN-induced angiogenesis, the mechanisms underlying their roles in angiogenesis have yet to be elucidated. PMN-induced Ets-1 expression was reduced by a monoclonal antibody against ICAM-1 but not E-selectin despite the inhibition of PMN-induced angiogenesis by both antibodies. Moreover, the stimulation of angiogenesis by H(2)O(2) without PMNs was inhibited by a monoclonal antibody to E-selectin but not ICAM-1. These findings suggested that ICAM-1 in endothelial cells may act as a signaling receptor to induce Ets-1 expression, whereas E-selectin seems to function in the formation of tubelike structures in vascular endothelial cell cultures.
Yasuda
Masako
M
Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
Shimizu
Shunichi
S
Ohhinata
Kyoko
K
Naito
Shinji
S
Tokuyama
Shogo
S
Mori
Yasuo
Y
Kiuchi
Yuji
Y
Yamamoto
Toshinori
T
D000818:Animals; D000906:Antibodies; D001011:Aorta / Q000166:cytology; D002374:Catalase / Q000494:pharmacology; D002417:Cattle; D002478:Cells, Cultured; D019040:E-Selectin / Q000378:metabolism*; D019332:Endothelin-1 / Q000235:genetics / Q000276:immunology; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology*; D005786:Gene Expression Regulation / Q000502:physiology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000276:immunology*; D009504:Neutrophils / Q000502:physiology*; D016376:Oligonucleotides, Antisense; D016877:Oxidants / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000494:pharmacology
D000906:Antibodies; D019040:E-Selectin; D019332:Endothelin-1; D016376:Oligonucleotides, Antisense; D016877:Oxidants; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase