van Dissel J T, Stikkelbroeck J J, Michel B C, Leijh P C, van Furth R
J Immunol. 1987 Jun 15;138(12):4428-34.
The aim of the present study was to determine whether the difference between the rate of intracellular killing of Salmonella typhimurium by macrophages of salmonella-resistant CBA and salmonella-susceptible C57BL/10 mice also holds for other salmonellae and other bacteria species. After in vivo phagocytosis, the initial rate of in vitro intracellular killing of S. typhimurium phagetype 505, S. typhimurium phagetype 510, and S. typhimurium M206 by macrophages of CBA mice amounted always to approximately 1.7 times the value found for macrophages of C57BL/10 mice (p less than 0.001), indicating that the difference in killing efficiency between CBA and C57BL/10 macrophages holds for various strains of S. typhimurium. However, some other salmonella species, i.e., S. dublin and S. heidelberg, as well as E. coli 054 and 02K1+, Listeria monocytogenes EGD and L347, and Staphylococcus aureus were killed equally efficiently by macrophages of both mouse strains. These findings indicate that the difference between the rates of intracellular killing by macrophages of salmonella-resistant CBA and salmonella-susceptible C57BL/10 does not hold for several other bacteria species and thus might be specific for S. typhimurium. Subsequent experiments showed that the in vivo proliferation of S. typhimurium 510 in the first 2 days after i.v. injection was 2.0-fold to 3.0-fold higher in the spleens and livers of C57BL/10 mice than in those of CBA mice, whereas the in vivo proliferation of S. dublin and S. heidelberg was between 1.0-fold to 1.4-fold higher in the C57BL/10 mice. These findings suggest that the differences between the rate of in vitro intracellular killing of salmonella by CBA and C57BL/10 macrophages are reflected in differences in the rate of in vivo proliferation of these microorganisms in CBA and C57BL/10 mice. To gain insight into the involvement of the oxidative metabolism of CBA and C57BL/10 macrophages in the difference in the rate of intracellular killing of S. typhimurium, the O2 consumption and H2O2 release by resident peritoneal macrophages was determined. The amplitudes of the respiratory burst and the release of H2O2 was identical in macrophages of the two mouse strains after triggering by either preopsonized heat-killed S. typhimurium or phorbol myristic acetate. These findings indicate that the mouse species-associated difference in the intracellular killing of S. typhimurium is not caused by a difference in the oxidative metabolism of CBA and C57BL/10 macrophages.
本研究的目的是确定对沙门氏菌具有抗性的CBA小鼠和对沙门氏菌敏感的C57BL/10小鼠的巨噬细胞对鼠伤寒沙门氏菌的细胞内杀伤率差异,是否也适用于其他沙门氏菌和其他细菌种类。体内吞噬后,CBA小鼠巨噬细胞对505型鼠伤寒沙门氏菌、510型鼠伤寒沙门氏菌和M206型鼠伤寒沙门氏菌的体外细胞内杀伤初始率,总是约为C57BL/10小鼠巨噬细胞的1.7倍(p小于0.001),这表明CBA和C57BL/10巨噬细胞在杀伤效率上的差异适用于各种鼠伤寒沙门氏菌菌株。然而,其他一些沙门氏菌种类,即都柏林沙门氏菌和海德堡沙门氏菌,以及大肠杆菌O54和O2K1+、单核细胞增生李斯特菌EGD和L347,还有金黄色葡萄球菌,在两种小鼠品系的巨噬细胞作用下被同等有效地杀伤。这些发现表明,对沙门氏菌具有抗性的CBA小鼠和对沙门氏菌敏感的C57BL/10小鼠的巨噬细胞在细胞内杀伤率上的差异,并不适用于其他几种细菌种类,因此可能是鼠伤寒沙门氏菌所特有的。后续实验表明,静脉注射后第1天和第2天,510型鼠伤寒沙门氏菌在C57BL/10小鼠脾脏和肝脏中的体内增殖比CBA小鼠高2.0倍至3.0倍,而都柏林沙门氏菌和海德堡沙门氏菌在C57BL/10小鼠中的体内增殖比CBA小鼠高1.0倍至1.4倍。这些发现表明,CBA和C57BL/10巨噬细胞对沙门氏菌的体外细胞内杀伤率差异,反映在这些微生物在CBA和C57BL/10小鼠体内增殖率的差异上。为了深入了解CBA和C57BL/10巨噬细胞的氧化代谢在鼠伤寒沙门氏菌细胞内杀伤率差异中的作用,测定了驻留腹膜巨噬细胞的耗氧量和过氧化氢释放量。在用预调理的热灭活鼠伤寒沙门氏菌或佛波酯肉豆蔻酸酯触发后,两种小鼠品系巨噬细胞的呼吸爆发幅度和过氧化氢释放量相同。这些发现表明,CBA和C57BL/10巨噬细胞氧化代谢的差异,并不是造成鼠伤寒沙门氏菌细胞内杀伤中与小鼠种类相关差异的原因。