Integrin alpha(M)beta(2)-mediated cell migration to fibrinogen and its recognition peptides

Leukocyte migration is the hallmark of inflammation. and integrin alpha (M) beta (2) and its ligand fibrinogen (Fg) are key participants in this cellul ar response. Cells expressing wild-type or mutant alpha (M)beta (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 P3 alpha (M)beta (2) recog nition peptides support a chemotactic response; (b) when the I domain of al pha (L) was replaced with the I domain of alpha (M), the chimeric receptor supported cell migration to Fg; however, the alpha (M) subunit, containing the I domain but lacking the beta (2) subunit, supported migration poorly, thus. the alpha I-M domain is necessary but nor sufficient to support chemo taxis, and efficient migration requires the P, subunit and ol,I domain; and (c) in addition to supporting cell migration, P2 enhanced alpha (M)beta (2 )-mediated chemotaxis to Fg and the P1 peptide. This activation was associa ted with exposure of the activation-dependent epitope recognized by monoclo nal antibody 7E3 and was observed also with human neutrophils. Taken togeth er, these data define specific molecular requirements for alpha (M)beta (2) to mediate cell migration to Fg derivatives and assign a novel proinflamma tory activity to the P2 peptide.