Ligation of lymphocyte function-associated antigen-1 on monocytes decreases very late antigen-4-mediated adhesion through a reactive oxygen species-dependent pathway
Ligation of lymphocyte function-associated antigen-1 on monocytes decreases very late antigen-4-mediated adhesion through a reactive oxygen species-dependent pathway
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DOI：
10.1182/blood-2004-05-1822
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发表时间：
2004-12-15
期刊：
影响因子：
20.3
通讯作者：
Shieh, CC
中科院分区：
文献类型：
--
作者：
Chuang, KP;Huang, YF;Shieh, CC
单核细胞-内皮细胞黏附在单核细胞转运中起重要作用，因此在免疫反应和包括动脉粥样硬化在内的炎症性疾病的发病机制中具有重要作用。在复杂的跨内皮细胞迁移过程中，单核细胞上不同整合素之间的相互作用可能是协调调节细胞黏附的关键。用单抗和重组细胞间黏附分子-1(ICAM-1)与单核细胞表面的淋巴细胞功能相关抗原-1(LFA-1)结合，发现VLA-4(VLA-4)介导的细胞与血管细胞黏附分子-1(VCAM-1)的黏附受到抑制，这种抑制作用依赖于活性氧(ROS)的存在。通过使用烟酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶的抑制剂而不是线粒体电子传输链或黄嘌呤氧化酶的抑制剂来抑制ROS的产生，发现这种抑制VLA-4介导的细胞结合的作用是由吞噬细胞NADPH氧化酶产生的ROS介导的。磷酸肌醇-3激酶和Akt的激活可能通过p47Phox磷酸化和Rac-1激活来介导这种NADPH氧化酶的激活。我们的结果提供了一条新的途径，使Ross在单核细胞的整合素串扰中发挥关键作用。在单核细胞运输过程中，这一信号通路可能对细胞从坚硬的停滞到滞育的转变很重要。(C)2004年，由美国血液病学会提供。
Monocyte-endothelial adhesion plays an important role in monocyte trafficking and hence is important for immune responses and pathogenesis of inflammatory diseases including atherosclerosis. The cross-talk between different integrins on monocytes may be crucial for a coordinated regulation of the cellular adhesion during the complex process of transendothelial migration. By using monoclonal antibodies and recombinant intercellular adhesion molecule 1 (ICAM-1) to engage lymphocyte function-associated antigen 1 (LFA-1) on monocytic cells, we found that the cellular adhesion to vascular cell adhesion molecule 1 (VCAM-1) mediated by very late antigen 4 (VLA-4) was suppressed after this treatment and the suppression depended on the presence of reactive oxygen species (ROSs). Inhibition of production of RoSs through the use of inhibitor of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, but not inhibitors of mitochondrial electron transport chain or xanthine oxidase, revealed that this suppression on VLA-4-mediated cellular binding was mediated by Ross produced by phagocyte NADPH oxidase. Activation of phosphoinositol-3 kinase and Akt appears to mediate this NADPH oxidase activation through p47 phox phosphorylation and Rac-1 activation. Our results provide a novel pathway in which Ross play a critical role in integrin cross-talk in monocytes. This signaling pathway may be important for cellular transition from firm arrest to diapedesis during monocyte trafficking. (C) 2004 by The American Society of Hematology.