González-Amaro R, Díaz-González F, Sánchez-Madrid F
Hospital Universitario de la Princesa, Universidad Autónoma de Madrid, Spain.
Drugs. 1998 Dec;56(6):977-88. doi: 10.2165/00003495-199856060-00003.
Cell adhesion molecules (CAM) have a key role in the inflammatory response. Selectins, integrins and immunoglobulin (Ig) gene superfamily adhesion receptors mediate the different steps of the migration of leucocytes from the blood-stream towards inflammatory foci. The activation of endothelial cells (EC) upregulates the expression of several CAM and triggers the interaction of these cells with leucocytes. Selectins are involved in the initial interactions (tethering/rolling) of leucocytes with activated endothelium, whereas integrins and Ig superfamily CAM mediate the firm adhesion of these cells and their subsequent extravasation. During rolling, leucocytes are activated through the intracellular signals generated by CAM and chemokine receptors. Blockade of the function or expression of CAM has emerged as a new therapeutic target in inflammatory diseases. Different drugs are able to interfere with cell adhesion phenomena. In addition, new antiadhesion therapeutic approaches (blocking monoclonal antibodies, soluble receptors, synthetic peptides, peptidomimetics, etc.) are currently in development.
细胞黏附分子(CAM)在炎症反应中起关键作用。选择素、整合素和免疫球蛋白(Ig)基因超家族黏附受体介导白细胞从血流向炎症灶迁移的不同步骤。内皮细胞(EC)的激活上调了几种CAM的表达,并触发这些细胞与白细胞的相互作用。选择素参与白细胞与活化内皮细胞的初始相互作用(拴系/滚动),而整合素和Ig超家族CAM介导这些细胞的牢固黏附及其随后的外渗。在滚动过程中,白细胞通过CAM和趋化因子受体产生的细胞内信号被激活。阻断CAM的功能或表达已成为炎症性疾病的新治疗靶点。不同的药物能够干扰细胞黏附现象。此外,新的抗黏附治疗方法(阻断单克隆抗体、可溶性受体、合成肽、肽模拟物等)目前正在研发中。