LIGAND BRIDGING MEDIATES INTEGRIN ALPHA-IIB-BETA-3 (PLATELET GPIIB-IIIA) DEPENDENT HOMOTYPIC AND HETEROTYPIC CELL-CELL INTERACTIONS

The aggregation of cells bearing recombinant integrin alpha-IIb-beta-3 (platelet GPIIb-IIIa) has been analyzed by two-color flow cytometry. As in normal platelets, aggregation requires functional alpha-IIb-beta-3, "activation" of alpha-IIb-beta-3, and fibrinogen (fg) binding to alpha-IIb-beta-3. Cellular aggregation required that both interacting cells express functional alpha-IIb-beta-3, because a binding defective mutant, alpha-IIb-beta-3 (D119 --> Y), failed to support interaction with wild type alpha-IIb-beta-3-bearing cells. In addition, cells bearing resting alpha-IIb-beta-3 were incorporated into aggregates formed by cells bearing a constitutively active mutant, alpha-IIb-beta-3 (beta-1-2), indicating that only one of the cells in an interacting pair must be activated. Finally, heterotypic interactions occurred between cells bearing activated alpha-IIb-beta-3 and cells bearing alpha-v-beta-3, 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 alpha-IIb-beta-3 (e.g., resting platelets) may be incorporated into aggregates formed by cells bearing activated alpha-IIb-beta-3, and alpha-IIb-beta-3 mediates heterotypic interactions with cells bearing other fg receptors.