Inhibition by insoluble immune complexes of both capacitative Ca2+ entry and Ca2+ mobilization by chemotactic agonists in human neutrophils.
Insoluble immune complexes (IIC) stimulate human neutrophils by binding to their FcR. It is known that they are able to release Ca2+ from intracellular stores but they induce little Ca2+ entry from the extracellular medium, a dissociation that cannot be explained within the framework of the capacitative model for Ca2+ entry, which is well established for these cells. We show here that IIC induce a strong and long-lasting inhibition of the Ca2+ pathway activated by emptying the Ca2+ stores (capacitative Ca2+ entry), which develops simultaneously with the activation of Ca2+ release from intracellular stores. This inhibition strongly resembles that previously described effected by FMLP and by phorbol dibutyrate, which seems to be mediated by phosphorylation. Inhibition by IIC, however, differs from that induced by FMLP and phorboldibutyrate in its lack of sensitivity to cytosolic-free calcium concentration and in its different sensitivity to the protein kinase inhibitors staurosporin and chelerythrine. It was also insensitive to the protein tyrosine kinase inhibitors genistein and herbimycin A. We also show that IIC inhibit Ca2+ mobilization induced by other agonists and that this inhibition is potentiated by the protein phosphatase inhibitor calyculin A. Our results therefore suggest that binding of IIC to the FcR activates a protein phosphorylation mechanism leading to a long-lasting inhibition of both capacitative Ca2+ entry and Ca2+ mobilization induced by other agonists such as FMLP, platelet-activating factor, or leukotriene B4.
Department of Biochemistry and Molecular Biology and Physiology, Faculty of Medicine, University of Valladolid, Spain.
M
M
Montero
A A
AA
Steil
M
M
Sanchez Crespo
J
J
Garcia-Sancho
J
J
Alvarez
D000936:Antigen-Antibody Complex / Q000737:chemistry / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000502:physiology*; D006801:Humans; D008345:Manganese / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism*; D010980:Platelet Membrane Glycoproteins / Q000502:physiology; D011956:Receptors, Cell Surface; D011961:Receptors, Fc / Q000502:physiology; D044042:Receptors, Formyl Peptide; D043562:Receptors, G-Protein-Coupled; D011971:Receptors, Immunologic / Q000502:physiology; D018102:Receptors, Leukotriene B4 / Q000502:physiology; D018000:Receptors, Peptide / Q000502:physiology
D000936:Antigen-Antibody Complex; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D011961:Receptors, Fc; D044042:Receptors, Formyl Peptide; D043562:Receptors, G-Protein-Coupled; D011971:Receptors, Immunologic; D018102:Receptors, Leukotriene B4; D018000:Receptors, Peptide; C039351:platelet activating factor receptor; D008345:Manganese; D002118:Calcium