Distinct roles for the α and β subunits in the functions of integrin αMβ2

Integrin alpha(M)beta(2) (Mac-1, CD11b/CD18) is a noncovalently linked heterodimer of alpha(M) and beta(2) subunits on the surface of leukocytes, where it plays a pivotal role in the adhesion and migration of these cells. Using HEK293 cells expressing alpha(M)beta(2) or the individual constituent chains on their surface, we analyzed the contributions of the alpha(M) or beta(2) subunits to functional responses mediated by the integrin. In cells expressing only alpha(M) or beta(2), the individual subunits were not associated with the endogenous integrins of the cells, and other partners for the subunits were not detected by surface labeling and immunoprecipitation under a variety of conditions. The alpha(M) cells mediated adhesion and spreading on a series of alpha(M)beta(2) ligands (fibrinogen, Factor X, iC3b, ICAM-1 (intercellular adhesion molecule-1), and denatured ovalbumin) but could not support cell migration to any of these. The spreading of the alpha(M) cells suggested an unanticipated linkage of this subunit to the cytoskeleton. The beta(2) cells supported migration and attachment but not spreading on a subset of the alpha(M)beta(2) ligands. The heterodimeric receptor and its individual subunits were purified from the cells by affinity chromatography and recapitulated the ligand binding properties of the corresponding cell lines. These data indicate that each subunit of alpha(M)beta(2) contributes distinct properties to alpha(M)beta(2) and that, in most but not all cases, the response of the integrin is a composite of the functions of its individual subunits.