IFN-gamma induces expression of Fc gamma RIII (CD16) on human eosinophils.
The extent to which eosinophils constitutively express FcRIII (CD16) is controversial. We were unable to detect this receptor on freshly isolated, peripheral blood eosinophils. The capacity of eosinophils to change their Fc gamma R expression in vitro has not been previously demonstrated. Culture with IFN-gamma for 1 to 2 days induced FcRIII expression on eosinophils. This effect was dose-dependent and significant at concentrations of 100 U/ml IFN-gamma and above. Expression of FcRI (CD64) and FcRII (CDw32) was also upregulated. These increases were inhibited by cycloheximide (10(-6) M), suggesting a requirement for protein synthesis, and dexamethasone (10(-6) M). Northern blot analysis demonstrated the presence of FcRIII mRNA in eosinophils cultured with IFN-gamma for 2 days but not in unstimulated eosinophils. By contrast, culture with IL-3 caused an up-regulation of eosinophil FcRII expression but did not induce expression of FcRI or FcRIII. The FcRIII expressed by eosinophils after IFN-gamma stimulation was functionally active, as shown by the triggering of eosinophil membrane depolarization and LTC4 generation by an anti-CD16 mAb. Treatment of IFN-gamma-stimulated eosinophils with phosphatidylinositol-specific phospholipase C reduced FcRIII expression, suggesting that, like neutrophils, eosinophils express the phosphatidylinositol glycan-linked form of this receptor. Therefore, this study demonstrates that IFN-gamma-treated eosinophils express a functionally active, phosphatidylinositol glycan-anchored form of FcRIII.
Hartnell
A
A
Department of Allergy and Clinical Immunology, National Heart and Lung Institute, London, UK.
Kay
A B
AB
Wardlaw
A J
AJ
D000943:Antigens, Differentiation / Q000032:analysis*; D003513:Cycloheximide / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism*; D007371:Interferon-gamma / Q000494:pharmacology*; D007377:Interleukin-3 / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism; D011961:Receptors, Fc / Q000032:analysis*; D017452:Receptors, IgG; D013189:SRS-A / Q000096:biosynthesis; D010738:Type C Phospholipases / Q000494:pharmacology
D000943:Antigens, Differentiation; D007074:Immunoglobulin G; D007377:Interleukin-3; D010716:Phosphatidylinositols; D011961:Receptors, Fc; D017452:Receptors, IgG; D013189:SRS-A; D003907:Dexamethasone; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003513:Cycloheximide; D010738:Type C Phospholipases