The role of tyrosine phosphorylation and Ca2+ accumulation in Fc gamma-receptor-mediated phagocytosis of human neutrophils.
When stimulated with an insoluble immune complex consisting of tetanus toxoid and human anti-tetanus toxoid IgG antibody, human neutrophils recognized the immune complex via Fc receptors (Fc gamma RII and Fc gamma RIIIB) on their plasma membranes, resulting in Ca2+ accumulation, and finally phagocytosed the immune complex. Ca2+ depletion experiments suggest that Ca2+ accumulation is essential for the maximal phagocytic activity. A tyrosine kinase inhibitor, genistein, inhibited the phagocytosis of immune complex. Genistein also inhibited both the later prolonged Ca2+ accumulation below 100 microM, and the initial rapid Ca2+ accumulation above 100 microM. Stimulation of human neutrophils by immune complexes through Fc gamma Rs caused tyrosine phosphorylation of multiple neutrophil proteins within 15 s, proceeding to an increase in the intracellular Ca2+ concentration. A similar pattern of tyrosine phosphorylation was observed when Fc gamma RII or Fc gamma RIIIB was aggregated by an anti-Fc gamma R monoclonal antibody and anti-mouse Ig. These results suggest that tyrosine phosphorylation mediates, at least in part, the later responses (Ca2+ accumulation and phagocytosis) of the cells and is an important early step in signaling via Fc gamma Rs.
D000936:Antigen-Antibody Complex / Q000276:immunology; D002118:Calcium / Q000378:metabolism*; D002614:Chelating Agents / Q000378:metabolism / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005453:Fluorescence; D019833:Genistein; D006801:Humans; D015151:Immunoblotting; D007074:Immunoglobulin G / Q000276:immunology; D007529:Isoflavones / Q000494:pharmacology; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism*; D010587:Phagocytosis / Q000187:drug effects; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011961:Receptors, Fc / Q000502:physiology*; D013744:Tetanus Toxin / Q000276:immunology; D014443:Tyrosine / Q000378:metabolism*
D000936:Antigen-Antibody Complex; D002614:Chelating Agents; D004791:Enzyme Inhibitors; D007074:Immunoglobulin G; D007529:Isoflavones; D011961:Receptors, Fc; D013744:Tetanus Toxin; D014443:Tyrosine; D004533:Egtazic Acid; D019833:Genistein; D011505:Protein-Tyrosine Kinases; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium