Fc gamma RII-mediated superoxide production by phagocytes is augmented by GM-CSF without a change in Fc gamma RII expression.
Freshly purified neutrophils and monocytes respond to multiple cross-linking of Fc gamma RII with the IgG1 monoclonal antibody, CIKM5, with a rapid rise in Ca(2+)i, but not with a respiratory burst, although superoxide is generated by these cells when stimulated with the chemotactic peptide, FMLP, or phorbol ester (TPA). Incubation in vitro for 30-60 min at 37 degrees C in medium + 0.1% FCS had no effect on the neutrophil superoxide response to CIKM5 but induced a weak monocyte response in 11/13 experiments. However, incubation with rhGM-CSF (10 ng/ml) under similar conditions induced a neutrophil respiratory burst in response to cross-linking Fc gamma RII in 12/14 experiments and enhanced the monocyte response by 181%. GM-CSF also enhanced the response of neutrophils and monocytes to FMLP by 308% and 165%, respectively. The response to TPA was not significantly enhanced by GM-CSF. rhIFN-gamma (100 mu/ml) was ineffective as a priming agent for all agonists tested in short-term incubations but augmented the monocyte response to CIKM5 after 5 d exposure in vitro. Whilst GM-CSF induced neutrophil superoxide production in response to cross-linking Fc gamma RII, there was no concomitant change in Fc gamma RII expression either in in vitro studies of neutrophils from healthy individuals or in in vivo studies of patients receiving GM-CSF. Stimulation of unprimed neutrophils with CIKM5 induced a rapid transient increase in intracellular calcium levels to 181% of resting levels. However, incubation with GM-CSF did not further augment the calcium transients above the stimulated level. The mechanism by which GM-CSF induces an enhanced respiratory burst in response to cross-linking of Fc gamma RII remains to be elucidated, but is not related to receptor expression or increases in receptor mediated calcium mobilization.
Roberts
P J
PJ
Department of Haematology, Faculty of Clinical Science, University College London, U.K.
Devereux
S
S
Pilkington
G R
GR
Linch
D C
DC
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000502:physiology; D000943:Antigens, Differentiation / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D018845:CD11 Antigens; D018821:CD18 Antigens; D017252:CD3 Complex; D002118:Calcium / Q000378:metabolism; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000494:pharmacology*; D006649:Histocompatibility Antigens / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007371:Interferon-gamma / Q000494:pharmacology; D017493:Leukocyte Common Antigens; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D010586:Phagocytes / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D011961:Receptors, Fc / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017452:Receptors, IgG; D016028:Receptors, Leukocyte-Adhesion / Q000276:immunology; D013481:Superoxides / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015854:Up-Regulation / Q000235:genetics / Q000502:physiology
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D000945:Antigens, Differentiation, T-Lymphocyte; D018845:CD11 Antigens; D018821:CD18 Antigens; D017252:CD3 Complex; D003115:Colony-Stimulating Factors; D006133:Growth Substances; D006649:Histocompatibility Antigens; D007074:Immunoglobulin G; D011948:Receptors, Antigen, T-Cell; D011961:Receptors, Fc; D017452:Receptors, IgG; D016028:Receptors, Leukocyte-Adhesion; D013481:Superoxides; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D017493:Leukocyte Common Antigens; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium