Ligand bridging mediates integrin α_IIbβ₃ (platelet GPIIB-IIIA) dependent homotypic and heterotypic cell-cell interactions

The aggregation of cells bearing recombinant integrin α_IIbβ₃ (platelet GPIIb-IIIa) has been analyzed by two-color flow cytometry. As in normal platelets, aggregation requires functional α_IIbβ₃, "activation" of α_IIbβ₃, and fibrinogen (fg) binding to α_IIbβ₃. Cellular aggregation required that both interacting cells express functional α_IIbβ₃, because a binding defective mutant, α_IIbβ₃ (D119 → Y), failed to support interaction with wild type α_IIbβ₃-bearing cells. In addition, cells bearing resting α_IIbβ₃ were incorporated into aggregates formed by cells bearing a constitutively active mutant, α_IIbβ₃ (β₁-2), indicating that only one of the cells in an interacting pair must be activated. Finally, heterotypic interactions occurred between cells bearing activated α_IIbβ₃ and cells bearing α_vβ₃, 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 α_IIbβ₃ (e.g., resting platelets) may be incorporated into aggregates formed by cells bearing activated α_IIbβ₃, and α_IIbβ₃ mediates heterotypic interactions with cells bearing other fg receptors.