Satoh M, Oshima H, Abe S, Yamazaki M, Mizuno D
Faculty of Pharmaceutical Sciences, Teikyo University, Kanagawa, Japan.
J Biol Response Mod. 1987 Oct;6(5):499-511.
The effects of systemic administrations of immune complex, complement activators, and insoluble particles on endogenous production of tumor necrosis factor (TNF) were investigated in mice. Production of serum TNF was triggered by i.v. injection of OK-432, a streptococcal preparation, and measured by in vitro L-929 cytotoxicity assay. Intravenous injection of IgG-opsonized sheep red blood cells (10(8)/mouse) enhanced OK-432-triggered TNF production significantly. This effect was maximal (about 30-fold enhancement) 1.5 to 3 h after the injection and disappeared within 10 h. Complement activators other than immune complex also possessed this activity. Zymosan (0.1 mg/mouse) enhanced OK-432-triggered TNF production maximally (about 25-fold) 3 to 6 h after its i.v. injection, its effect lasting for 10 h, and disappearing within 24 h. Heat-aggregated IgG and cobra venom factor also had similar enhancing effects. In addition, systemic pretreatment with insoluble particles enhanced OK-432-triggered TNF production. The enhancement by latex beads (2 microliters volume of solid/mouse) was maximal (about 60-fold) 3 to 6 h after their i.v. injection, was sustained for at least 20 h, and disappeared within 48 h. Glass beads, dextran beads, alum, silica, and carbon particles all had similar enhancing effects. Based on these results, the in vivo scavenger function of macrophages, as well as direct activation with cytokines, may participate in priming for endogenous production of TNF; alternatively, particles or macromolecules which can be scavenged by macrophages may activate macrophages and prime for TNF production.
研究了在小鼠体内全身给予免疫复合物、补体激活剂和不溶性颗粒对肿瘤坏死因子（TNF）内源性产生的影响。静脉注射链球菌制剂OK-432可引发血清TNF的产生，并通过体外L-929细胞毒性试验进行测定。静脉注射IgG调理的绵羊红细胞（10⁸/只小鼠）可显著增强OK-432引发的TNF产生。该效应在注射后1.5至3小时达到最大值（约增强30倍），并在10小时内消失。除免疫复合物外的补体激活剂也具有这种活性。酵母聚糖（0.1mg/只小鼠）静脉注射后3至6小时可最大程度地增强OK-432引发的TNF产生（约25倍），其作用持续10小时，并在24小时内消失。热聚集IgG和眼镜蛇毒因子也有类似的增强作用。此外，用不溶性颗粒进行全身预处理可增强OK-432引发的TNF产生。乳胶珠（2微升固体体积/只小鼠）静脉注射后3至6小时增强作用最大（约60倍），持续至少20小时，并在48小时内消失。玻璃珠、葡聚糖珠、明矾、二氧化硅和碳颗粒都有类似的增强作用。基于这些结果，巨噬细胞的体内清除功能以及细胞因子的直接激活可能参与了TNF内源性产生的启动；或者，可被巨噬细胞清除的颗粒或大分子可能激活巨噬细胞并启动TNF的产生。
