β2 Integrins-Multi-Functional Leukocyte Receptors in Health and Disease

beta 2 integrins are heterodimeric surface receptors composed of a variable alpha (CD11a-CD11d) and a constant beta (CD18) subunit and are specifically expressed by leukocytes. The alpha subunit defines the individual functional properties of the corresponding beta 2 integrin, but all beta 2 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 beta 2 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 beta 2 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, beta 2 integrins have received growing interest as targets in the treatment of autoimmune diseases. Moreover, beta 2 integrin activity on leukocytes has been implicated in tumor development.