Haidaris C G, Bonventre P F
J Immunol. 1982 Aug;129(2):850-5.
Leishmania donovani, the causative agent of visceral leishmaniasis, infects macrophages (M phi ) of susceptible vertebrates. Immunologically activated M phi are leishmanicidal, but the mechanisms involved in the killing process are not well defined. We sought to investigate the role of reactive oxygen intermediates in the killing of L. donovani. Both the free-swimming promastigote and the intracellular amastigote forms were found to be susceptible to killing in vitro by hydrogen peroxide and other oxygen intermediates. Upon phagocytosis by mouse peritoneal M phi, promastigotes elicited a significantly stronger respiratory burst compared with amastigotes as measured by release of superoxide anion. Although amastigotes do not elicit a strong burst of M phi oxidative metabolism during the initial phagocytic event, immunologically activated M phi that acquired leishmanicidal capacity could be triggered to release substantial amounts of H2O2. Hence, the development of leishmanicidal capacity was correlated temporally with enhanced H2O2 generation by the M phi. In contrast, M phi that lost their ability to release significant amounts of H2O2 after several days in culture were unable to eliminate their parasite burden. Catalase markedly inhibited the elimination of amastigotes by lymphokine-stimulated M phi. In toto, the results implicate reactive oxygen intermediates in killing of the tissue form of L. donovani by its host cell, the mononuclear phagocyte.
杜氏利什曼原虫是内脏利什曼病的病原体，可感染易感脊椎动物的巨噬细胞（M phi）。免疫激活的M phi具有杀利什曼原虫的作用，但杀伤过程所涉及的机制尚不清楚。我们试图研究活性氧中间体在杀死杜氏利什曼原虫中的作用。发现游动的前鞭毛体和细胞内无鞭毛体形式在体外均易受过氧化氢和其他氧中间体的杀伤。通过超氧阴离子的释放测量，与无鞭毛体相比，前鞭毛体被小鼠腹膜M phi吞噬后引发的呼吸爆发明显更强。尽管无鞭毛体在初始吞噬事件期间不会引发M phi氧化代谢的强烈爆发，但获得杀利什曼原虫能力的免疫激活M phi可被触发释放大量H2O2。因此，杀利什曼原虫能力的发展在时间上与M phi产生H2O2的增加相关。相反，在培养数天后失去释放大量H2O2能力的M phi无法消除其寄生虫负荷。过氧化氢酶显著抑制淋巴因子刺激的M phi对无鞭毛体的清除。总体而言，结果表明活性氧中间体参与宿主细胞单核吞噬细胞对杜氏利什曼原虫组织形式的杀伤。
