Leu R W, Zhou A Q, Kennedy M J, Shannon B J
Biomedical Division, Samuel Roberts Nobel Foundation, Inc., Ardmore, OK 73402.
J Immunol. 1991 Feb 15;146(4):1233-9.
Studies originally designed to assess the putative role of endogenous C5 in macrophage activation for antibody-dependent cellular cytotoxicity (ADCC) yielded unanticipated results. Resident and inflammatory peritoneal macrophages from C5-deficient AKR mice were found to have significantly lower capacity for FcR-dependent ADCC activation and phagocytosis of IgG-opsonized SRBC targets than did C5-competent C3HeB/FeJ (C3H) mice. Reconstitution of the ADCC response of AKR macrophages was accomplished initially with C5-sufficient C3H mouse serum, which suggested that endogenous C5 may be required for ADCC activation. However, further investigation largely eliminated C5 involvement in that a heat-labile component of C5-deficient AKR serum was shown to be active in the reconstitution of ADCC activation of AKR macrophages. Macrophages from AKR mice were found to have significantly lower levels of C1q mRNA synthesis, endogenous C1q levels, and C1q secretion than did C3H mouse macrophages as determined by Northern blot, Western blot, and presynthetic radiolabeling analysis, respectively. The addition of purified exogenous C1q to IgG-opsonized SRBC targets fully reconstituted ADCC activation for AKR inflammatory peritoneal macrophages to levels of normally FcR-responsive C3H macrophages. Similarly, exogenous C1q augmented FcR-dependent phagocytosis of AKR macrophages but had no effect on macrophages from responsive C3H mice. Our results indicate that AKR mice have a deficiency for FcR-dependent cellular cytotoxicity and phagocytosis that is related to their low potential for C1q synthesis and secretion rather than to their established genetic deficiency for C5 synthesis. We tentatively conclude that endogenous C1q is required as an accessory molecule for macrophage FcR-dependent effector functions and that C5 is not a prerequisite for ADCC activation.
最初旨在评估内源性C5在巨噬细胞激活以介导抗体依赖性细胞毒性（ADCC）中假定作用的研究产生了意外结果。发现C5缺陷型AKR小鼠的驻留性和炎性腹膜巨噬细胞与具有C5的C3HeB/FeJ（C3H）小鼠相比，其FcR依赖性ADCC激活能力以及对IgG调理的SRBC靶标的吞噬能力显著更低。最初用C5充足的C3H小鼠血清实现了AKR巨噬细胞ADCC反应的重建，这表明内源性C5可能是ADCC激活所必需的。然而，进一步研究在很大程度上排除了C5的参与，因为已证明C5缺陷型AKR血清中的一种热不稳定成分在重建AKR巨噬细胞的ADCC激活中具有活性。分别通过Northern印迹、Western印迹和合成前放射性标记分析确定，发现AKR小鼠的巨噬细胞C1q mRNA合成水平、内源性C1q水平和C1q分泌水平比C3H小鼠巨噬细胞显著更低。向IgG调理的SRBC靶标中添加纯化的外源性C1q可将AKR炎性腹膜巨噬细胞的ADCC激活完全重建至正常FcR反应性C3H巨噬细胞的水平。同样，外源性C1q增强了AKR巨噬细胞的FcR依赖性吞噬作用，但对反应性C3H小鼠的巨噬细胞没有影响。我们的结果表明，AKR小鼠存在FcR依赖性细胞毒性和吞噬作用缺陷，这与其C1q合成和分泌的低潜力有关，而不是与其已确定的C5合成基因缺陷有关。我们初步得出结论，内源性C1q作为巨噬细胞FcR依赖性效应功能的辅助分子是必需的，并且C5不是ADCC激活的先决条件。
