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Published online before print January 20, 2005
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Article |
RIIIB stimulation promotes
1 integrin activation in human neutrophils
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 |
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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
R) on activation of integrins in human neutrophils. Cross-linking of Fc
RIIA induced an increase in surface expression of
2 integrins but had no effect on
1 integrins. In contrast, cross-linking of Fc
RIIIB not only increased
2 integrins on the cell surface but also induced
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
RIIIB-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, Fc
RIIIB-induced
1 integrin activation was not blocked by PP2 or LY294002. It was, however, enhanced by Piceatannol. After Fc
RIIIB cross-linking, colocalization of Fc
RIIIB and active
1 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
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
RIIIB with
1 integrins.
Key Words: Fc receptors inside-out signaling PI-3K ERK Syk calcium
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