Contribution of soluble intercellular adhesion molecule-1 to the migration of vascular smooth muscle cells.
Soluble intercellular adhesion molecule-1 (sICAM-1), a circulating form of ICAM-1, has been known to be involved in the development of vascular diseases that are associated with vascular smooth muscle cell migration, such as hypertension and atherosclerosis. Here we investigated the contributions of sICAM-1 in promoting vascular migration in rat aortic smooth muscle cells (RASMCs). sICAM-1 increased RASMC migration, and this response was stronger in spontaneously hypertensive rats (SHRs) than in Wistar Kyoto (WKY) rats. The CD11a, CD11b, and CD18 subunits of ICAM-1 receptors were expressed in both SHRs and WKY rats; however, the expression levels of CD18 and CD11b were greater in SHRs than in WKY rats. The neutralization of the receptor subunits with anti-CD11a and -CD18 antibodies abolished the sICAM-1-increased migration. The treatment of inhibitors of spleen tyrosine kinase (Syk) and p38 mitogen-activated protein kinase suppressed the sICAM-1-stimulated migration of RASMCs. sICAM-1 also increased the sprout formation in aortic rings on Matrigel, and this response was inhibited by treatment with these inhibitors. The results suggest that sICAM-1 play crucial roles in vascular cell function through Syk pathways, and that the altered responses of sICAM-1 in RASMCs from SHRs may be mediated by the increased expression of the CD18 receptor.
Lee
Hwan Myung
HM
Department of Medicine, College of Medicine, Konkuk University, 322 Danwol-dong, Chungju-city, Chungbuk 380-701, South Korea.
Kim
Hyo Jin
HJ
Won
Kyung-Jong
KJ
Choi
Wahn Soo
WS
Lee
Kyung-Yung
KY
Bae
Young Min
YM
Park
Pyo-Jam
PJ
Park
Tae-Kyu
TK
Lee
Yun Lyul
YL
Lee
Chang-Kwon
CK
Kim
Bokyung
B
D000818:Animals; D001011:Aorta / Q000166:cytology / Q000378:metabolism; D040881:CD11a Antigen / Q000235:genetics / Q000378:metabolism; D039481:CD11b Antigen / Q000235:genetics / Q000378:metabolism; D018821:CD18 Antigens / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology*; D015870:Gene Expression; D006973:Hypertension / Q000150:complications; D066298:In Vitro Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D000072377:Syk Kinase
D040881:CD11a Antigen; D039481:CD11b Antigen; D018821:CD18 Antigens; D047908:Intracellular Signaling Peptides and Proteins; D018799:Intercellular Adhesion Molecule-1; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C000606898:Syk protein, rat