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Published online before print January 20, 2005
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RIIIB stimulation promotes ß1 integrin activation in human neutrophils
Immunology Department, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City
1 Correspondence: Department of Immunology, Instituto de Investigaciones BiomédicasUNAM, Apdo. Postal 70228, Cd. Universitaria, México D.F.04510, Mexico. E-mail: carosal{at}servidor.unam.mx
The molecular stimuli involved in receptor-induced integrin activation are still poorly defined. We have investigated the role of receptors for the Fc portion of immunoglobulin G molecules (Fc
Key Words: Fc receptors inside-out signaling PI-3K ERK Syk calcium
R) on activation of integrins in human neutrophils. Cross-linking of Fc
RIIA induced an increase in surface expression of ß2 integrins but had no effect on ß1 integrins. In contrast, cross-linking of Fc
RIIIB not only increased ß2 integrins on the cell surface but also induced ß1 integrin activation, as indicated by an increase in binding to fibronectin and the appearance of an activation epitope detected by the monoclonal antibody 15/7. The Fc
RIIIB-induced increase of ß2 integrins required Src-family tyrosine kinases, Syk kinase, and phosphatidylinositol-3 kinase (PI-3K), as the corresponding, specific inhibitors, PP2, Piceatannol, and LY294002
RIIIB-induced ß1 integrin activation was not blocked by PP2 or LY294002
RIIIB cross-linking, colocalization of Fc
RIIIB and active ß1 integrins was detected on the neutrophil membrane. These data show, for the first time, that cross-linking of Fc
RIIIB induces an inside-out signaling pathway that leads to ß1 integrin activation. This activation is independent of Src-family kinases, and PI-3K and may be induced in part by the interaction of Fc
RIIIB with ß1 integrins.
Copyright © 2005 by the Society for Leukocyte Biology.
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