van de Winkel J G, Boonen G J, Janssen P L, Vlug A, Hogg N, Tax W J
Department of Medicine, University Hospital Nijmegen, The Netherlands.
Scand J Immunol. 1989 Jan;29(1):23-31. doi: 10.1111/j.1365-3083.1989.tb01095.x.
We investigated the cytotoxicity of human monocytes mediated by two types of receptors for the Fc portion of IgG, Fc gamma RI and Fc gamma RII. Erythrocytes sensitized with human IgG (EA-human IgG) were used to assay Fc gamma RI function, and erythrocytes sensitized with mouse IgG1 (EA-mouse IgG1) were used to assay Fc gamma RII. Both types of Fc gamma R were observed to mediate antibody-dependent cell-mediated cytotoxicity (ADCC), which was further characterized by using different monoclonal anti-Fc gamma R antibodies (MoAb) and monomeric IgG. Lysis of EA-human IgG was inhibited by both monomeric human IgG and mouse IgG2a in a dose-dependent way, and also by anti-Fc gamma RI MoAb 10.1. Cytolysis of EA-mouse IgG1 was inhibited by monomeric mouse IgG1 and by two anti-Fc gamma RII MoAb, IV.3 and CIKM5. Antibodies of the mouse IgG2b isotype affected neither type of ADCC. The effectiveness of cytotoxicity mediated by either of the Fc gamma R was studied by means of targets sensitized with a calibrated number of IgG molecules. At least 20 times more IgG molecules per target cell were necessary to obtain half-maximal cytotoxicity mediated by Fc gamma RII than for Fc gamma RI-mediated cytolysis. Furthermore, the previously described polymorphism of Fc gamma RII was also reflected in Fc gamma RII-dependent cytotoxicity. These studies demonstrate that Fc gamma RII can mediate ADCC, although a higher degree of target cell sensitization is required than for Fc gamma RI-mediated ADCC.
我们研究了由两种IgG Fc段受体，即FcγRI和FcγRII介导的人单核细胞的细胞毒性。用人IgG致敏的红细胞（EA-人IgG）用于检测FcγRI功能，用小鼠IgG1致敏的红细胞（EA-小鼠IgG1）用于检测FcγRII。观察到两种类型的FcγR均介导抗体依赖性细胞介导的细胞毒性（ADCC），通过使用不同的抗FcγR单克隆抗体（MoAb）和单体IgG对其进行了进一步表征。EA-人IgG的裂解受到单体人IgG和小鼠IgG2a的剂量依赖性抑制，也受到抗FcγRI MoAb 10.1的抑制。EA-小鼠IgG1的细胞溶解受到单体小鼠IgG1以及两种抗FcγRII MoAb，IV.3和CIKM5的抑制。小鼠IgG2b同种型的抗体对两种类型的ADCC均无影响。通过用校准数量的IgG分子致敏的靶标研究了由任一FcγR介导的细胞毒性的有效性。与FcγRI介导的细胞溶解相比，每个靶细胞获得半数最大细胞毒性所需的IgG分子数量至少要多20倍。此外，先前描述的FcγRII多态性也反映在FcγRII依赖性细胞毒性中。这些研究表明，FcγRII可以介导ADCC，尽管与FcγRI介导的ADCC相比，需要更高程度的靶细胞致敏。
