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 cellular 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 P2 alpha(M)beta(2) recognition peptides support a chemotactic response; (b) when the I domain of alpha(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(M)I domain is necessary but not sufficient to support chemotaxis, and efficient migration requires the beta(2) subunit and alpha(M)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 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 alpha(M)beta(2) to mediate cell migration to Fg derivatives and assign a novel proinflammatory activity to the P2 peptide.
Forsyth
C B
CB
Joseph J. Jacobs Center for Thrombosis and Vascular Biology, and the Department of Molecular Cardiology, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
Solovjov
D A
DA
Ugarova
T P
TP
Plow
E F
EF
D002634:Chemotaxis, Leukocyte / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005338:Fibrin Fibrinogen Degradation Products / Q000494:pharmacology*; D005340:Fibrinogen / Q000494:pharmacology*; D006801:Humans; D016177:Macrophage-1 Antigen / Q000235:genetics / Q000378:metabolism*
D005338:Fibrin Fibrinogen Degradation Products; D016177:Macrophage-1 Antigen; C046678:fibrinopeptide D; D005340:Fibrinogen