Leukocyte integrin activation.

Abstract

The three leukocyte integrins LFA-1, CR3/Mac-1 and p150,95 are heter-odimeric molecules each comprising a unique α subunit noncovalently associated with a common β 2 subunit (1). A feature of the N terminus of the α subunit is the seven domains of ∼60 amino acids (domains I-VII) of which the last three or four are homologous to divalent cation binding or EF-hand-type sites. Integrins are known to require bound divalent cations such as Mg2+ and/or Ca2+ in order to function and it is to this region that they bind (2,3). The roles of these molecules in immune functions are best characterized for LFA-1 (CD11a/CD18) and CR3(CD11b/ CD18). Antibody blocking studies have demonstrated a key role for LFA-1 in many cellular interactions of leukocytes and CR3 is important in functions such as myeloid cell phagocytosis, adherence to activated endothelium, and Chemotaxis (4–6). These activities are thought to represent in vitro correlates of the response to tissue inflammation.