Thompson Paul W, Randi Anna M, Ridley Anne J
Ludwig Institute for Cancer Research, Royal Free and University College School of Medicine, London, United Kingdom.
J Immunol. 2002 Jul 15;169(2):1007-13. 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.
ICAM - 1和ICAM - 2是整合素结合免疫球蛋白超家族粘附分子，对白细胞穿过内皮单层细胞的迁移非常重要。已知ICAM - 1交联可激活小GTP酶RhoA并诱导内皮细胞中应力纤维的形成，但ICAM - 2信号传导尚未得到研究。在本研究中，我们比较了ICAM - 1和ICAM - 2在人脐静脉内皮细胞（HUVECs）中的信号传导和定位。尽管ICAM - 1和ICAM - 2都与顶端微绒毛中的肌动蛋白结合蛋白埃兹蛋白共定位，但只有ICAM - 1在交联后与埃兹蛋白共定位。与ICAM - 1不同，ICAM - 2不激活RhoA或改变肌动蛋白细胞骨架组织。有趣的是，ICAM - 1刺激已知的早期反应基因c - fos的转录。此外，它上调rhoA表达，表明它在RhoA激活后激活了一个正反馈途径。这些结果表明，在内皮细胞中，ICAM - 1而非ICAM - 2能快速刺激涉及RhoA的信号反应。
