Targeting leukocyte integrins in human diseases

Abstract: 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 in-volved in diverse clinical disorders, ranging from asthma to atherosclerosis. Antagonists that inter-fere 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 tri-als (e.g., ischemia-reperfusion disorders and trans-plantation). However, recent successes of integrin antagonists in psoriasis, inflammatory bowel dis-ease, and multiple sclerosis demonstrate the tre-mendous potential of antiadhesion therapy di-rected at leukocyte integrins. This article will re-view the role of the leukocyte integrins in the inflammatory process, approaches to targeting leu-kocyte integrins and their ligands, and the result