Signal transduction events and Fc gamma R engagement in human neutrophils stimulated with immune complexes.
Signal transduction events have been evaluated in human neutrophils stimulated with immune complexes consisting of polyclonal rabbit antibody complexed with BSA. Immune complexes induced dose-related O2- responses, but very small increases in intracellular calcium ([Ca2+]i) levels were observed, in contrast to FMLP-stimulated cells. Measurements employing [45Ca2+] demonstrated that calcium influx and efflux in cells stimulated with immune complexes was substantially less than fluxes found in FMLP-stimulated cells. With respect to inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) formation under conditions in which the O2- responses to immune complexes or FMLP were similar, the Ins(1,4,5)P3 response to immune complexes was much smaller (by 65%) as compared to that induced by FMLP. Although pertussis toxin-treated cells showed a greatly diminished O2- response (by 89%) to FMLP, the response to immune complexes was largely resistant (only 26% reduction) to the inhibitory effects of this toxin. Antibodies to Fc gamma R indicated that engagement of Fc gamma RII and Fc gamma RIII, but not Fc gamma RI, receptors was related to the O2- response of neutrophils to immune complexes. O2- formation occurred in neutrophils incubated with Staphylococcus aureus cell walls bearing antibodies to Fc gamma RII or Fc gamma RIII. These data indicate that, in human neutrophils stimulated with immune complexes, signal transduction events involve engagement of Fc gamma RII and Fc gamma RIII. The O2- response is largely pertussis-toxin insensitive, is not associated with a significant increase in levels of [Ca2+]i, and is associated with relatively little formation of Ins(1,4,5)P3. This is in contrast to cells stimulated with FMLP in which O2- responses are largely pertussis toxin-sensitive and associated with large increases in [Ca2+]i as well as formation of Ins(1,4,5)P3. Signal transduction events involving Fc gamma R appear to be quite different from those events related to engagement of FMLP receptors.
Walker
B A
BA
Department of Pathology, University of Michigan School of Medicine, Ann Arbor 48109-0602.
Hagenlocker
B E
BE
Stubbs
E B
EB
Sandborg
R R
RR
Agranoff
B W
BW
Ward
P A
PA
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex / Q000502:physiology*; D000943:Antigens, Differentiation / Q000502:physiology*; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis; D008954:Models, Biological; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000276:immunology / Q000494:pharmacology; D009504:Neutrophils / Q000276:immunology*; D011961:Receptors, Fc / Q000502:physiology*; D017452:Receptors, IgG; D015398:Signal Transduction / Q000276:immunology*; D013481:Superoxides / Q000378:metabolism
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D000943:Antigens, Differentiation; D011961:Receptors, Fc; D017452:Receptors, IgG; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015544:Inositol 1,4,5-Trisphosphate