Stevenson M M, Huang D Y, Podoba J E, Nowotarski M E
Centre for the Study of Host Resistance, McGill University, Montreal, Quebec, Canada.
Infect Immun. 1992 Mar;60(3):1193-201. doi: 10.1128/iai.60.3.1193-1201.1992.
Macrophage activation was examined in resistant C57BL/6 and susceptible A/J mice during the course of blood-stage infection with Plasmodium chabaudi AS. Three parameters of macrophage activation (lipopolysaccharide [LPS]- and malaria antigen-induced tumor necrosis factor [TNF] production in vitro, phorbol myristate acetate [PMA]-induced production of oxygen metabolites in vitro, and Ia antigen expression) were assessed during infection in populations of peritoneal and splenic macrophages recovered from infected mice of the two strains. The peak level of LPS-induced TNF production in vitro by splenic macrophages from both infected C57BL/6 and infected A/J mice occurred on day 7, which was 3 days before the peak of parasitemia. Although the kinetics of TNF production in vitro in response to either LPS, soluble malaria antigen, or intact parasitized erythrocytes varied in some of the other macrophage populations during infection, there was no significant difference in the peak level of production. Peritoneal and splenic macrophages from infected C57BL/6 mice exhibited significantly increased PMA-induced production of H2O2 in vitro on day 7. Peritoneal macrophages from infected A/J mice also exhibited significant PMA-induced H2O2 production on day 7, while production by splenic macrophages from these hosts was not increased in comparison with production by cells from normal animals. Only peritoneal macrophages from infected C57BL/6 mice produced significantly increased levels of O2-, and this occurred on day 7 postinfection. Ia antigen expression by both peritoneal and splenic macrophages from resistant C57BL/6 and susceptible A/J mice was significantly increased during P. chabaudi AS infection. However, the percentage of Ia+ peritoneal macrophages on days 8 and 10 postinfection and Ia+ splenic macrophages on day 3 postinfection was significantly higher in C57BL/6 than in A/J mice. Thus, these results demonstrate that macrophages from P. chabaudi AS-infected A/J mice exhibit defects in oxygen metabolism and Ia antigen expression which may contribute to the susceptibility of these hosts to this intraerythrocytic parasite. The cause-and-effect relationship between these defects and the susceptibility of A/J mice to P. chabaudi AS is unknown.
在感染恰氏疟原虫AS血期的过程中，对具有抗性的C57BL/6小鼠和易感的A/J小鼠体内巨噬细胞的激活情况进行了检测。从这两个品系的感染小鼠中分离出腹腔巨噬细胞和脾巨噬细胞群体，在感染期间评估了巨噬细胞激活的三个参数（体外脂多糖[LPS]和疟疾抗原诱导的肿瘤坏死因子[TNF]产生、佛波酯[PMA]诱导的体外氧代谢产物产生以及Ia抗原表达）。感染的C57BL/6小鼠和感染的A/J小鼠的脾巨噬细胞在体外LPS诱导的TNF产生的峰值水平均出现在第7天，这比寄生虫血症峰值提前3天。尽管在感染期间，其他一些巨噬细胞群体对LPS、可溶性疟疾抗原或完整的寄生红细胞产生TNF的体外动力学有所不同，但产生的峰值水平没有显著差异。感染的C57BL/6小鼠的腹腔和脾巨噬细胞在第7天体外PMA诱导的H2O2产生显著增加。感染的A/J小鼠的腹腔巨噬细胞在第7天也表现出显著的PMA诱导的H2O2产生，而这些宿主的脾巨噬细胞与正常动物细胞相比，其产生量没有增加。只有感染的C57BL/6小鼠的腹腔巨噬细胞产生的O2-水平显著增加，且发生在感染后第7天。在恰氏疟原虫AS感染期间，抗性C57BL/6小鼠和易感A/J小鼠的腹腔和脾巨噬细胞的Ia抗原表达均显著增加。然而，感染后第8天和第10天的Ia+腹腔巨噬细胞百分比以及感染后第3天的Ia+脾巨噬细胞百分比在C57BL/6小鼠中显著高于A/J小鼠。因此，这些结果表明，来自感染恰氏疟原虫AS的A/J小鼠的巨噬细胞在氧代谢和Ia抗原表达方面存在缺陷，这可能导致这些宿主对这种红细胞内寄生虫易感。这些缺陷与A/J小鼠对恰氏疟原虫AS的易感性之间的因果关系尚不清楚。
