Journal of Leukocyte Biology
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A more recent version of this article appeared on May 1, 2005

Published online before print January 20, 2005
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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0504310


Received for publication May 27, 2004.
Revised December 15, 2004.
Accepted for publication December 19, 2004.


Article

Fc{gamma}RIIIB stimulation promotes {beta}1 integrin activation in human neutrophils

Alejandro Ortiz-Stern and Carlos Rosales @

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

@ To whom correspondence should be addressed. E-mail: carosal{at}servidor.unam.mx.


   Abstract

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 {beta}2 integrins but had no effect on {beta}1 integrins. In contrast, cross-linking of Fc{gamma}RIIIB not only increased {beta}2 integrins on the cell surface but also induced {beta}1 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 {beta}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, Fc{gamma}RIIIB-induced {beta}1 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 {beta}1 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 {beta}1 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 {beta}1 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.