Integrin α(M)β(2)-Mediated Cell Migration to Fibrinogen and Its Recognition Peptides

Leukocyte migration is the hallmark of inflammation, and integrin α(M)β(2) and its ligand fibrinogen (Fg) are key participants in this cellular response. Cells expressing wild-type or mutant α(M)β(2) and Fg or its derivatives have been used to dissect the molecular requirements for this receptor–ligand pair to mediate cell migration. The major conclusions are that (a) Fg, its D fragment, and its P1 and P2 α(M)β(2) recognition peptides support a chemotactic response; (b) when the I domain of α(L) was replaced with the I domain of α(M), the chimeric receptor supported cell migration to Fg; however, the α(M) subunit, containing the I domain but lacking the β(2) subunit, supported migration poorly, thus, the α(M)I domain is necessary but not sufficient to support chemotaxis, and efficient migration requires the β(2) subunit and α(M)I domain; and (c) in addition to supporting cell migration, P2 enhanced α(M)β(2)-mediated chemotaxis to Fg and the P1 peptide. This activation was associated with exposure of the activation-dependent epitope recognized by monoclonal antibody 7E3 and was observed also with human neutrophils. Taken together, these data define specific molecular requirements for α(M)β(2) to mediate cell migration to Fg derivatives and assign a novel proinflammatory activity to the P2 peptide.