Hundt M, Schubert J, de Haas M, Zielinska-Skowronek M, Schmidt R E
Department of Medicine, Hannover Medical School, Germany.
Blood. 1994 Jun 15;83(12):3574-80.
Neutrophils from patients with paroxysmal nocturnal hemoglobinuria (PNH) show a deficiency for the glycosylphosphatidylinositol- (GPI) linked Fc gamma receptor IIIb (Fc gamma RIIIb, CD16). The functional consequences of this defect are not clear. Here, we examined Fc gamma RIIIb-deficient neutrophils for their activation via Fc gamma receptors. Hydrogen peroxide (H2O2) production and change of intracellular free calcium [Ca2+]i were used as parameters for cell activation. Fc gamma RII and Fc gamma RIIIb stimulation was reached by cross-linking using fragments of monoclonal antibodies or incubation with monoclonal IgG cryoglobulin complexes. In parallel to the deficiency of Fc gamma RIIIb expression, H2O2 production and [Ca2+]i influx were decreased after cross-linking of Fc gamma RIIIb in PNH neutrophils compared with that for normal neutrophils. Stimulation via Fc gamma RII was not affected. Cryoglobulin complexes previously shown to activate normal neutrophils predominantly via Fc gamma RIIIb stimulated PNH neutrophils at a level not significantly weaker than controls. But this activation was mediated only via Fc gamma RII as shown by blocking studies. The results suggest that the loss of GPI-anchored Fc gamma RIIIb is functionally replaced by Fc gamma RII during the immune complex stimulation of PNH neutrophils. Therefore, the equipment of neutrophils with pleomorphic Fc gamma receptors prevents an immunodeficiency in PNH.
阵发性睡眠性血红蛋白尿（PNH）患者的中性粒细胞显示糖基磷脂酰肌醇（GPI）连接的Fcγ受体IIIb（FcγRIIIb，CD16）缺乏。这种缺陷的功能后果尚不清楚。在此，我们检查了缺乏FcγRIIIb的中性粒细胞通过Fcγ受体的激活情况。使用过氧化氢（H2O2）产生和细胞内游离钙[Ca2+]i的变化作为细胞激活的参数。通过使用单克隆抗体片段交联或与单克隆IgG冷球蛋白复合物孵育来实现FcγRII和FcγRIIIb刺激。与FcγRIIIb表达缺乏平行，与正常中性粒细胞相比，PNH中性粒细胞中FcγRIIIb交联后H2O2产生和[Ca2+]i内流减少。通过FcγRII的刺激不受影响。先前显示主要通过FcγRIIIb激活正常中性粒细胞的冷球蛋白复合物刺激PNH中性粒细胞的水平并不明显弱于对照组。但如阻断研究所示，这种激活仅通过FcγRII介导。结果表明，在PNH中性粒细胞的免疫复合物刺激过程中，GPI锚定的FcγRIIIb的缺失在功能上被FcγRII所取代。因此，具有多形性Fcγ受体的中性粒细胞装备可预防PNH中的免疫缺陷。
