Modulation of human polymorphonuclear leukocyte IgG Fc receptors and Fc receptor-mediated functions by IFN-gamma and glucocorticoids.
Human polymorphonuclear neutrophils (PMN) normally express two distinct types of IgG Fc gamma R, the 40-kDa Fc gamma R referred to as Fc gamma RII and the low affinity 50- to 70-kDa Fc gamma R designated Fc gamma RIII. A third type of Fc gamma R, the 72-kDa high affinity receptor known as Fc gamma RI, is also detectable on PMN that have been activated by IFN-gamma. Using mAb that discriminate among the three known types of Fc gamma R, we examined the effects of IFN-gamma and glucocorticoids on human PMN Fc gamma R expression. We also studied effects of IFN-gamma and the synthetic glucocorticoid dexamethasone (DEX) on antibody-dependent cytotoxicity (ADCC) of chicken erythrocytes and phagocytosis of IgG-coated ox RBC by human PMN. In 20 donors studied, we found that treatment of PMN with 400 U/ml IFN-gamma induced a 9- to 20-fold increase in the number of Fc gamma RI sites per cell, and DEX inhibited this induction of Fc gamma RI by 39 to 73%. Similarly, DEX significantly reduced the IFN-gamma stimulation of ADCC and phagocytosis. IFN-gamma had no effect on expression of Fc gamma RII or Fc gamma RIII. Fc gamma RI and Fc gamma RII expression was unaltered by 24 h of treatment with DEX alone, but Fc gamma RIII expression was sometimes increased by about 20% on PMN cultured with DEX. Nevertheless, we found a small but significant inhibition of ADCC and phagocytosis by 200 nM DEX. Our results indicate that Fc gamma RI plays a major but not exclusive role in the regulation of ADCC and phagocytosis by IFN-gamma and DEX.
Petroni
K C
KC
Department of Physiology, Dartmouth Medical School, Hanover, NH 03756.
Shen
L
L
Guyre
P M
PM
D000276:Adjuvants, Immunologic / Q000037:antagonists & inhibitors; D000328:Adult; D000954:Antigens, Surface / Q000032:analysis; D003176:Complement C3 / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D004306:Dose-Response Relationship, Immunologic; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology*; D007700:Kinetics; D016177:Macrophage-1 Antigen; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D011951:Receptors, Complement / Q000187:drug effects; D011961:Receptors, Fc / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D017452:Receptors, IgG
D000276:Adjuvants, Immunologic; D000954:Antigens, Surface; D003176:Complement C3; D005938:Glucocorticoids; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D016177:Macrophage-1 Antigen; D011951:Receptors, Complement; D011961:Receptors, Fc; D017452:Receptors, IgG; D003907:Dexamethasone; D007371:Interferon-gamma