PDF(Sci-hub)
Abstract：
β2 integrins are heterodimeric surface receptors composed of a variable α (CD11a-CD11d) and a constant β (CD18) subunit and are specifically expressed by leukocytes. The α subunit defines the individual functional properties of the corresponding β2 integrin, but all β2 integrins show functional overlap. They mediate adhesion to other cells and to components of the extracellular matrix (ECM), orchestrate uptake of extracellular material like complement-opsonized pathogens, control cytoskeletal organization, and modulate cell signaling. This review aims to delineate the tremendous role of β2 integrins for immune functions as exemplified by the phenotype of LAD-I (leukocyte adhesion deficiency 1) patients that suffer from strong recurrent infections. These immune defects have been largely attributed to impaired migratory and phagocytic properties of polymorphonuclear granulocytes. The molecular base for this inherited disease is a functional impairment of β2 integrins due to mutations within the CD18 gene. LAD-I patients are also predisposed for autoimmune diseases. In agreement, polymorphisms within the CD11b gene have been associated with autoimmunity. Consequently, β2 integrins have received growing interest as targets in the treatment of autoimmune diseases. Moreover, β2 integrin activity on leukocytes has been implicated in tumor development.
摘要：
β2整联蛋白是异二聚体表面受体,由可变α(CD11a-CD11d)和恒定β(CD18)亚基组成,并由白细胞特异性表达。α亚基定义了相应β2整联蛋白的各个功能特性，但所有的β2整合素显示功能重叠。它们介导与其他细胞和细胞外基质（ECM）成分的粘附，协调细胞外物质的摄取，如补体调理病原体，控制细胞骨架组织，并调节细胞信号传导。这篇综述旨在描述β2整合素对免疫功能的巨大作用，例如患有强烈复发性感染的LAD-I（白细胞粘附缺陷1）患者的表型。这些免疫缺陷主要归因于多形核粒细胞的迁移和吞噬特性受损。这种遗传性疾病的分子基础是由于CD18基因内的突变引起的β2整合素的功能损害。LAD-I患者也倾向于自身免疫性疾病。在协议中,CD11b基因内的多态性与自身免疫有关。因此,β2整联蛋白作为自身免疫疾病治疗中的靶标受到越来越多的关注。此外，β2整联蛋白对白细胞的活性与肿瘤的发展有关。
