Integrin α_Mβ₂-Mediated Cell Migration to Fibrinogen and Its Recognition Peptides

Leukocyte migration is the hallmark of inflammation, and integrin α_Mβ₂ and its ligand fibrinogen (Fg) are key participants in this cellular response. Cells expressing wild-type or mutant α_Mβ₂ 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_Mβ₂ 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 β₂ subunit, supported migration poorly, thus, the α_MI domain is necessary but not sufficient to support chemotaxis, and efficient migration requires the β₂ subunit and α_MI domain; and (c) in addition to supporting cell migration, P2 enhanced α_Mβ₂-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_Mβ₂ to mediate cell migration to Fg derivatives and assign a novel proinflammatory activity to the P2 peptide.