Intercellular Adhesion Molecule (ICAM)-1, But Not ICAM-2, Activates RhoA and Stimulates c-fos and rhoA Transcription in Endothelial Cells

• Published in: The Journal of immunology (1950) Vol. 169; no. 2; pp. 1007 - 1013
• Main Authors: Thompson, Paul W, Randi, Anna M, Ridley, Anne J
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15.07.2002
• Subjects: Actin Cytoskeleton - metabolism; Actins - metabolism; Antigens, CD - immunology; Antigens, CD - metabolism; Antigens, CD - physiology; Cell Adhesion Molecules - immunology; Cell Adhesion Molecules - metabolism; Cell Adhesion Molecules - physiology; Cells, Cultured; Cross-Linking Reagents - metabolism; Endothelium, Vascular - cytology; Endothelium, Vascular - metabolism; Gene Expression Regulation - immunology; Genes, fos - immunology; Humans; Immune Sera - metabolism; Immune Sera - pharmacology; Intercellular Adhesion Molecule-1 - immunology; Intercellular Adhesion Molecule-1 - metabolism; Intercellular Adhesion Molecule-1 - physiology; Microfilament Proteins - metabolism; rhoA GTP-Binding Protein - biosynthesis; rhoA GTP-Binding Protein - genetics; rhoA GTP-Binding Protein - metabolism; Transcription, Genetic - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.169.2.1007

ICAM-1 and -2 are integrin-binding Ig superfamily adhesion molecules that are important for leukocyte transmigration across endothelial monolayers. ICAM-1 cross-linking is known to activate the small GTPase RhoA and induce stress fiber formation in endothelial cells, but ICAM-2 signaling has not been investigated. In this study, we compare ICAM-1 and ICAM-2 signaling and localization in HUVECs. Although ICAM-1 and ICAM-2 both localize with the actin-binding protein moesin in apical microvilli, only ICAM-1 colocalizes with moesin after cross-linking. Unlike ICAM-1, ICAM-2 does not activate RhoA or alter actin cytoskeletal organization. Interestingly, ICAM-1 stimulates transcription of c-fos, a known early response gene. In addition, it up-regulates rhoA expression, suggesting that it activates a positive feedback pathway after RhoA activation. These results indicate that in endothelial cells, ICAM-1, but not ICAM-2, rapidly stimulates signaling responses involving RhoA.