Jiang H, Rummage J A, Stewart C A, Herriott M J, Kolosova I, Kolosov M, Leu R W
Oklahoma Medical Research Foundation, Noble Center for Biomedical Research, Oklahoma City 73104-5046, USA.
Cell Immunol. 1996 May 25;170(1):34-40. doi: 10.1006/cimm.1996.0131.
The role of endogenously synthesized complement subcomponent C1q on autocrine binding of tumor necrosis factors (TNF-alpha) and on TNF-alpha receptor (TNF-R) mRNA synthesis by mouse macrophages was investigated. Activation of C3H mouse peritoneal macrophages (C3H-PM phi) by Lipid A induced TNF-alpha and nitric oxide (NO) to kill tumor targets. Such activation also increased macrophage-endogenous C1q synthesis and secretion in a dose-dependent fashion. Antibody for C1q markedly inhibited C3H-PM phi NO production in response to Lipid A, but had no effect on TNF-alpha production. C3H-PM phi treated with C1q or Lipid A displayed increased TNF-R mRNA synthesis and in combination with Lipid A and anti-C1q antibody inhibited TNF-R and nitric oxide synthase (NOS) mRNA synthesis compared with Lipid A only, but had no effect on TNF mRNA synthesis. In vitro treatment of C3H-PM phi with C1q also increased TNF-alpha binding to their surfaces. Taken together, the data indicate that endogenously synthesized C1q is operative in promoting TNF-R mRNA synthesis and resultant autocrine binding of TNF-alpha for induction of NOS in the process of NO-mediated tumor cytotoxicity by Lipid A-activated macrophages.
研究了内源性合成的补体亚成分C1q对肿瘤坏死因子（TNF-α）自分泌结合以及对小鼠巨噬细胞TNF-α受体（TNF-R）mRNA合成的作用。脂多糖激活C3H小鼠腹腔巨噬细胞（C3H-PM phi）可诱导TNF-α和一氧化氮（NO）以杀伤肿瘤靶标。这种激活还以剂量依赖方式增加巨噬细胞内源性C1q的合成与分泌。C1q抗体显著抑制C3H-PM phi对脂多糖刺激产生的NO，但对TNF-α的产生无影响。用C1q或脂多糖处理的C3H-PM phi显示TNF-R mRNA合成增加，与仅用脂多糖相比，脂多糖与抗C1q抗体联合使用可抑制TNF-R和一氧化氮合酶（NOS）mRNA合成，但对TNF mRNA合成无影响。体外使用C1q处理C3H-PM phi也增加了TNF-α与其表面的结合。综上所述，数据表明内源性合成的C1q在促进TNF-R mRNA合成以及由此产生的TNF-α自分泌结合以诱导脂多糖激活的巨噬细胞在NO介导的肿瘤细胞毒性过程中诱导NOS方面发挥作用。
