Graziano R F, Erbe D V, Fanger M W
Department of Microbiology, Dartmouth Medical School, Hanover, NH 03756.
J Immunol. 1989 Dec 15;143(12):3894-900.
To further understand the mechanism(s) of antibody-dependent cell-mediated cytotoxicity (ADCC) by various effector populations, we have examined the extracellular Ca++ and Mg++ requirements for ADCC performed by lymphocytes, monocytes, polymorphonuclear leukocytes and peritoneal macrophages. We have used the anti-Fc gamma R-bearing hybridoma cell lines (HC) as self directed targets for ADCC to analyse the triggering ability of each of the three defined Fc gamma R; Fc gamma RI, Fc gamma RII, and Fc gamma RIII. Lymphocyte killing of the anti-Fc gamma RIII bearing HC (HC 3G8) was Ca++ dependent, but Mg++ independent. In contrast, monocytes and PMN killed the anti-Fc gamma RI- (HC 32) and the anti-Fc gamma RII- (HC IV.3) bearing HC in a Mg++-dependent, Ca++-independent fashion. In addition, freshly prepared monocytes were able to kill HC 3G8 in a Mg++-dependent, Ca++-independent fashion, indicating that low levels of Fc gamma RIII may be functionally detected on monocytes. Peritoneal macrophages were able to kill all three of the anti-Fc gamma R bearing HC in a Mg++-dependent, Ca++-independent fashion. Thus, the same target is lysed by myeloid cells in the presence of Mg++ without Ca++ and by lymphoid cells in the presence of Ca++ without Mg++. These results suggest that at least two distinct mechanisms of ADCC exist that depend on the type of effector cell mediating antibody-dependent killing and not necessarily on the Fc gamma R type triggered.
为了进一步了解不同效应细胞群体介导的抗体依赖性细胞介导的细胞毒性（ADCC）机制，我们研究了淋巴细胞、单核细胞、多形核白细胞和腹腔巨噬细胞进行ADCC时对细胞外钙离子（Ca++）和镁离子（Mg++）的需求。我们使用携带抗FcγR的杂交瘤细胞系（HC）作为ADCC的自身导向靶标，以分析三种已定义的FcγR（FcγRI、FcγRII和FcγRIII）各自的触发能力。携带抗FcγRIII的HC（HC 3G8）的淋巴细胞杀伤作用依赖于Ca++，但不依赖于Mg++。相反，单核细胞和多形核白细胞以依赖Mg++、不依赖Ca++的方式杀伤携带抗FcγRI的HC（HC 32）和携带抗FcγRII的HC（HC IV.3）。此外，新鲜制备的单核细胞能够以依赖Mg++、不依赖Ca++的方式杀伤HC 3G8，这表明单核细胞上可能存在功能上可检测到的低水平FcγRIII。腹腔巨噬细胞能够以依赖Mg++、不依赖Ca++的方式杀伤所有三种携带抗FcγR的HC。因此，相同的靶标在没有Ca++但有Mg++存在时被髓样细胞裂解，而在没有Mg++但有Ca++存在时被淋巴细胞裂解。这些结果表明，至少存在两种不同的ADCC机制，这取决于介导抗体依赖性杀伤的效应细胞类型，而不一定取决于触发的FcγR类型。
