Ligand bridging mediates integrin αIIbβ3 (platelet GPIIB-IIIA) dependent homotypic and heterotypic cell-cell interactions

Meinrad P. Gawaz, Joseph C. Loftus, Mary Lynn Bajt, Mony M. Frojmovic, Edward F. Plow, Mark H. Ginsberg

Research output: Contribution to journalArticlepeer-review

102 Scopus citations

Abstract

The aggregation of cells bearing recombinant integrin αIIbβ3 (platelet GPIIb-IIIa) has been analyzed by two-color flow cytometry. As in normal platelets, aggregation requires functional αIIbβ3, "activation" of αIIbβ3, and fibrinogen (fg) binding to αIIbβ3. Cellular aggregation required that both interacting cells express functional αIIbβ3, because a binding defective mutant, αIIbβ3 (D119 → Y), failed to support interaction with wild type αIIbβ3-bearing cells. In addition, cells bearing resting αIIbβ3 were incorporated into aggregates formed by cells bearing a constitutively active mutant, αIIbβ31-2), indicating that only one of the cells in an interacting pair must be activated. Finally, heterotypic interactions occurred between cells bearing activated αIIbβ3 and cells bearing αvβ3, a fg-binding integrin present on endothelial and tumor cells. Thus, ligand bridging between fg-binding integrins represents a mechanism of cell-cell interaction, cells bearing resting αIIbβ3 (e.g., resting platelets) may be incorporated into aggregates formed by cells bearing activated αIIbβ3, and αIIbβ3 mediates heterotypic interactions with cells bearing other fg receptors.

Original languageEnglish (US)
Pages (from-to)1128-1134
Number of pages7
JournalJournal of Clinical Investigation
Volume88
Issue number4
DOIs
StatePublished - 1991

Keywords

  • Fibrinogen
  • Hemostasis
  • Platelet aggregation
  • RGD
  • Thrombosis

ASJC Scopus subject areas

  • Medicine(all)

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