Petroni K C, Shen L, Guyre P M
Department of Physiology, Dartmouth Medical School, Hanover, NH 03756.
J Immunol. 1988 May 15;140(10):3467-72.
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.
人类多形核中性粒细胞（PMN）通常表达两种不同类型的IgG FcγR，即40 kDa的FcγR，称为FcγRII，以及低亲和力的50至70 kDa的FcγR，称为FcγRIII。第三种类型的FcγR，即72 kDa的高亲和力受体，称为FcγRI，在经γ干扰素激活的PMN上也可检测到。使用能区分三种已知类型FcγR的单克隆抗体，我们研究了γ干扰素和糖皮质激素对人类PMN FcγR表达的影响。我们还研究了γ干扰素和合成糖皮质激素地塞米松（DEX）对鸡红细胞抗体依赖性细胞毒性（ADCC）以及人类PMN对IgG包被的牛红细胞吞噬作用的影响。在研究的20名供体中，我们发现用400 U/mlγ干扰素处理PMN会使每个细胞上FcγRI位点的数量增加9至20倍，而DEX可将这种FcγRI的诱导作用抑制39%至73%。同样，DEX显著降低了γ干扰素对ADCC和吞噬作用的刺激。γ干扰素对FcγRII或FcγRIII的表达没有影响。单独用地塞米松处理24小时，FcγRI和FcγRII的表达未改变，但在用DEX培养的PMN上，FcγRIII的表达有时会增加约20%。然而，我们发现200 nM DEX对ADCC和吞噬作用有轻微但显著的抑制作用。我们的结果表明，FcγRI在γ干扰素和DEX对ADCC和吞噬作用的调节中起主要但非唯一的作用。
