McCabe R E, Mullins B T
Department of Medicine, Martinez Veterans Administration Medical Center, CA 94553.
J Immunol. 1990 Mar 15;144(6):2384-8.
Activated macrophages are thought to kill Trypanosoma cruzi, which lack catalase, by the generation of hydrogen peroxide. We investigated triggering of the respiratory burst of activated macrophages induced by phagocytosis of virulent T. cruzi, bloodform trypomastigotes, amastigotes obtained from spleens, and tissue culture organisms; and of relatively nonvirulent epimastigotes. All stages of T. cruzi prompted the release of less than 10% of hydrogen peroxide released by activated macrophages when stimulated with PMA or Candida. Superoxide anion production was not stimulated by PMA or Candida in activated macrophages nor was there a significant qualitative reduction of nitroblue tetrazolium induced by ingestion of virulent T. cruzi. Opsonization of T. cruzi with specific antibody did not promote the release of hydrogen peroxide or the reduction of nitroblue tetrazolium. Similar results were observed with activated spleen macrophages. Incubation of activated macrophages with catalase, catalase and superoxide dismutase, sodium benzoate with or without catalase, and respiratory burst-exhausting PMA failed to inhibit the killing of T. cruzi in vitro. These results indicate that 1) virulent opsonized or unopsonized T. cruzi do not trigger a respiratory burst by activated macrophages and 2) oxygen-independent killing of T. cruzi is of prime importance.
活化的巨噬细胞被认为通过产生过氧化氢来杀死缺乏过氧化氢酶的克氏锥虫。我们研究了由吞噬强毒克氏锥虫、血液型锥鞭毛体、从脾脏获得的无鞭毛体以及组织培养生物体；以及相对无毒的上鞭毛体所诱导的活化巨噬细胞呼吸爆发的触发情况。克氏锥虫的所有阶段在被佛波酯（PMA）或白色念珠菌刺激时，促使释放的过氧化氢量少于活化巨噬细胞释放量的10%。在活化巨噬细胞中，PMA或白色念珠菌不会刺激超氧阴离子的产生，摄入强毒克氏锥虫也不会导致硝基蓝四唑的显著定性减少。用特异性抗体对克氏锥虫进行调理不会促进过氧化氢的释放或硝基蓝四唑的减少。活化的脾巨噬细胞也观察到类似结果。用过氧化氢酶、过氧化氢酶和超氧化物歧化酶、有或没有过氧化氢酶的苯甲酸钠以及耗尽呼吸爆发的PMA孵育活化巨噬细胞，均未能抑制体外对克氏锥虫的杀伤。这些结果表明：1）强毒的调理或未调理的克氏锥虫不会触发活化巨噬细胞的呼吸爆发；2）克氏锥虫的非氧依赖性杀伤至关重要。
