Journal of Leukocyte Biology
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Originally published online as doi:10.1189/jlb.0504310 on January 20, 2005

Published online before print January 20, 2005
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(Journal of Leukocyte Biology. 2005;77:787-799.)
© 2005 by Society for Leukocyte Biology

Fc{gamma}RIIIB stimulation promotes ß1 integrin activation in human neutrophils

Alejandro Ortiz-Stern and Carlos Rosales1

Immunology Department, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City

1 Correspondence: Department of Immunology, Instituto de Investigaciones Biomédicas–UNAM, 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{gamma}R) on activation of integrins in human neutrophils. Cross-linking of Fc{gamma}RIIA induced an increase in surface expression of ß2 integrins but had no effect on ß1 integrins. In contrast, cross-linking of Fc{gamma}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{gamma}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, completely blocked it. Contrary to this, Fc{gamma}RIIIB-induced ß1 integrin activation was not blocked by PP2 or LY294002. It was, however, enhanced by Piceatannol. After Fc{gamma}RIIIB cross-linking, colocalization of Fc{gamma}RIIIB and active ß1 integrins was detected on the neutrophil membrane. These data show, for the first time, that cross-linking of Fc{gamma}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{gamma}RIIIB with ß1 integrins.

Key Words: Fc receptors • inside-out signaling • PI-3K • ERK • Syk • calcium







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Copyright © 2005 by the Society for Leukocyte Biology.