Fc gammaRIIIB stimulation promotes beta1 integrin activation in human neutrophils.
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 gammaR) on activation of integrins in human neutrophils. Cross-linking of Fc gammaRIIA induced an increase in surface expression of beta2 integrins but had no effect on beta1 integrins. In contrast, cross-linking of Fc gammaRIIIB not only increased beta2 integrins on the cell surface but also induced beta1 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 gammaRIIIB-induced increase of beta2 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 gammaRIIIB-induced beta1 integrin activation was not blocked by PP2 or LY294002. It was, however, enhanced by Piceatannol. After Fc gammaRIIIB cross-linking, colocalization of Fc gammaRIIIB and active beta1 integrins was detected on the neutrophil membrane. These data show, for the first time, that cross-linking of Fc gammaRIIIB induces an inside-out signaling pathway that leads to beta1 integrin activation. This activation is independent of Src-family kinases, and PI-3K and may be induced in part by the interaction of Fc gammaRIIIB with beta1 integrins.
Ortiz-Stern
Alejandro
A
Immunology department, Instituto de Investigaciones Biomédicas, Apdo. Postal 70228, Cd. Universitaria, México D.F.-04510, Mexico.
Rosales
Carlos
C
D000328:Adult; D015703:Antigens, CD; D002867:Chromones / Q000494:pharmacology; D003432:Cross-Linking Reagents; D004791:Enzyme Inhibitors / Q000494:pharmacology; D058851:GPI-Linked Proteins; D006801:Humans; D019012:Integrin beta1 / Q000276:immunology / Q000378:metabolism*; D009025:Morpholines / Q000494:pharmacology; D018375:Neutrophil Activation; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D017452:Receptors, IgG / Q000819:agonists*; D015398:Signal Transduction / Q000187:drug effects; D013267:Stilbenes / Q000494:pharmacology; D015854:Up-Regulation
D015703:Antigens, CD; D002867:Chromones; D003432:Cross-Linking Reagents; D004791:Enzyme Inhibitors; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D019012:Integrin beta1; D009025:Morpholines; D017452:Receptors, IgG; D013267:Stilbenes; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C041525:3,3',4,5'-tetrahydroxystilbene; D011505:Protein-Tyrosine Kinases