Distinct tyrosine kinase activation and Triton X-100 insolubility upon Fc gamma RII or Fc gamma RIIIB ligation in human polymorphonuclear leukocytes. Implications for immune complex activation of the respiratory burst.
Two tyrosine kinase-dependent pathways exist for activation of the respiratory burst by polymorphonuclear leukocyte (PMN) immunoglobulin G Fc receptors. Direct ligation of Fc gamma RII activates the respiratory burst, but ligation of the glycan phosphoinositol-linked Fc gamma RIIIB does not. Instead, this receptor and the integrin complement receptor CR3 synergize in activation of the respiratory burst (Zhou, M.-J., and Brown, E. J. (1994) J. Cell Biol. 125, 1407-1416). Here we show that direct ligation of Fc gamma RII leads to activation and Triton X-100 insolubility of the Src family kinase Fgr, without effect on the related myeloid Src family member Hck. In contrast, adhesion of PMN via Fc gamma RIIIB leads to activation and Triton X-100 insolubility of Hck but not Fgr. The exclusive association of Fc gamma RIIIB with Hck activation and Triton insolubility is not solely a result of its glycan phosphoinositol anchor, since decay accelerating factor (CD55), another prominent glycan phosphoinositol-anchored PMN protein, is associated with Fgr insolubility to a greater extent than Hck. Ligation of decay accelerating factor, with or without coligation of CR3, does not activate the PMN respiratory burst. Coligation of Fc gamma RIIIB with Fc gamma RII overcomes the pertussis toxin inhibition of H2O2 production in response to direct ligation of Fc gamma RII. These data support the hypothesis that activation of Hck upon Fc gamma RIIIB ligation has a role in generation of the synergistic respiratory burst.
Zhou
M J
MJ
Division of Infectious Diseases, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Lublin
D M
DM
Link
D C
DC
Brown
E J
EJ
D000936:Antigen-Antibody Complex / Q000378:metabolism*; D004789:Enzyme Activation; D006801:Humans; D009504:Neutrophils / Q000201:enzymology / Q000378:metabolism*; D017830:Octoxynol / Q000737:chemistry*; D011505:Protein-Tyrosine Kinases / Q000737:chemistry / Q000378:metabolism*; D017452:Receptors, IgG / Q000378:metabolism*; D016897:Respiratory Burst; D015398:Signal Transduction; D012995:Solubility
D000936:Antigen-Antibody Complex; D017452:Receptors, IgG; D017830:Octoxynol; D011505:Protein-Tyrosine Kinases