Yonekawa Karyn, Harlan John M
Division of Nephrology, Department of Pediatrics, University of Washington, Seattle, WA, USA.
J Leukoc Biol. 2005 Feb;77(2):129-40. doi: 10.1189/jlb.0804460. Epub 2004 Nov 17.
As our understanding of integrins as multifunctional adhesion and signaling molecules has grown, so has their recognition as potential therapeutic targets in human diseases. Leukocyte integrins are of particular interest in this regard, as they are key molecules in immune-mediated and inflammatory processes and are thus critically involved in diverse clinical disorders, ranging from asthma to atherosclerosis. Antagonists that interfere with integrin-dependent leukocyte trafficking and/or post-trafficking events have shown efficacy in multiple preclinical models, but these have not always predicted success in subsequent clinical trials (e.g., ischemia-reperfusion disorders and transplantation). However, recent successes of integrin antagonists in psoriasis, inflammatory bowel disease, and multiple sclerosis demonstrate the tremendous potential of antiadhesion therapy directed at leukocyte integrins. This article will review the role of the leukocyte integrins in the inflammatory process, approaches to targeting leukocyte integrins and their ligands, and the results of completed clinical trials.
随着我们对整合素作为多功能黏附及信号分子的理解不断深入，它们作为人类疾病潜在治疗靶点的认可度也在提高。在这方面，白细胞整合素尤其受关注，因为它们是免疫介导和炎症过程中的关键分子，因此严重参与了从哮喘到动脉粥样硬化等多种临床疾病。干扰整合素依赖性白细胞转运和/或转运后事件的拮抗剂在多个临床前模型中已显示出疗效，但这些疗效在随后的临床试验中（如缺血再灌注疾病和移植）并非总能预测成功。然而，整合素拮抗剂最近在银屑病、炎症性肠病和多发性硬化症中的成功证明了针对白细胞整合素的抗黏附疗法的巨大潜力。本文将综述白细胞整合素在炎症过程中的作用、靶向白细胞整合素及其配体的方法以及已完成的临床试验结果。
