Integrin αMβ2-mediated cell migration to fibrinogen and its recognition peptides

Christopher B. Forsyth, Dmitry A. Solovjov, Tatiana P. Ugarova, Edward F. Plow

Research output: Contribution to journalArticlepeer-review

105 Scopus citations

Abstract

Leukocyte migration is the hallmark of inflammation, and integrin αMβ2 and its ligand fibrinogen (Fg) are key participants in this cellular response. Cells expressing wild-type or mutant αMβ2 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 αMβ2 recognition peptides support a chemotactic response; (b) when the I domain of αL was replaced with the I domain of αM, the chimeric receptor supported cell migration to Fg; however, the αM subunit, containing the I domain bur lacking the β2 subunit, supported migration poorly, thus, the αMI domain is necessary but not sufficient to support chemotaxis, and efficient migration requires the β2 subunit and αMI domain; and (c) in addition to supporting cell migration, P2 enhanced αMβ2-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 αMβ2 to mediate cell migration to Fg derivatives and assign a novel proinflammatory activity to the P2 peptide.

Original languageEnglish (US)
Pages (from-to)1123-1133
Number of pages11
JournalJournal of Experimental Medicine
Volume193
Issue number10
DOIs
StatePublished - May 21 2001
Externally publishedYes

Keywords

  • Adhesion molecules
  • CD11b/CD18
  • Fibrinogen
  • Inflammation
  • Integrin

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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