FcRIIIB stimulation promotes 1 integrin activation in human neutrophils

Abstract: The molecular stimuli involved in re-ceptor-induced integrin activation are still poorly defined. We have investigated the role of receptors for the Fc portion of immunoglobulin G molecules (FcR) on activation of integrins in human neutro-phils. Cross-linking of FcRIIA induced an in-crease in surface expression of 2 integrins but had no effect on 1 integrins. In contrast, cross-linking of FcRIIIB not only increased 2 inte-grins on the cell surface but also induced 1 inte-grin activation, as indicated by an increase in bind-ing to fibronectin and the appearance of an activation epitope detected by the monoclonal an-tibody 15/7. The FcRIIIB-induced increase of 2 integrins required Src-family tyrosine kinases, Syk kinase, and phosphatidylinositol-3 kinase (PI-3K), as the corresponding, specific inhibitors, PP2, Piceatannol, and LY294002, completely blocked it. Contrary to this, FcRIIIB-induced 1 integrin activation was not blocked by PP2 or LY294002. It was, however, enhanced by Piceatannol. After FcRIIIB cross-linking, colocalization of FcRIIIB and active 1 integrins was detected on the neu-trophil membrane. These data show, for the first time, that cross-linking of FcRIIIB induces an inside-out signaling pathway that leads to 1 inte-grin activation. This activation is independent of Src-family kinases, and PI-3K and may be induced in part by the interaction of FcRIIIB with 1 integrins. J. Leukoc. Biol. 77: 000–000; 2005