Johnson W C, Cluff C W, Goff W L, Wyatt C R
Animal Disease Research Unit, USDA-ARS, Pullman, Washington 99164-7030, USA.
Ann N Y Acad Sci. 1996 Jul 23;791:136-47. doi: 10.1111/j.1749-6632.1996.tb53520.x.
Products released from activated macrophages have been demonstrated to have microbicidal activity against a variety of microorganisms. Reactive oxygen intermediates (ROI) and reactive nitrogen intermediates (RNI) have been shown to affect the induction of degenerate (crisis) forms of Plasmodium spp. Polyamines are degraded into acrolein which has also been shown to be toxic to Plasmodium spp. We have investigated the possibility that these products act similarly with Babesia bovis. Crisis forms of B. bovis developed in erythrocyte cultures after the introduction of supernatants containing ROI, RNI, and acrolein. Xanthine degradation by xanthine oxidase leads to the formation of superoxide anion, hydrogen peroxide, and hydroxyl radicals. The degradation in the presence of B. bovis was toxic to the parasite. The toxicity was partially reversed by the addition of the ROI scavenger catalase. However, H2O2 added directly had little effect, suggesting a role for the other ROI products. Spermine degradation by polyamine oxidase and direct addition of acrolein was toxic in a dose-dependent manner. Finally, spontaneous generation of nitric oxide from sodium nitroprusside or S-nitroso-N-acetyl-penicillamine was also toxic in a dose-dependent manner. These data lead us to suggest a role for activated macrophages in the primary immune response against B. bovis.
已证明活化巨噬细胞释放的产物对多种微生物具有杀菌活性。活性氧中间体(ROI)和活性氮中间体(RNI)已被证明会影响疟原虫属退化(危机)形式的诱导。多胺被降解为丙烯醛,丙烯醛也已被证明对疟原虫属有毒。我们研究了这些产物对牛巴贝斯虫是否有类似作用的可能性。在引入含有ROI、RNI和丙烯醛的上清液后,红细胞培养物中出现了牛巴贝斯虫的危机形式。黄嘌呤氧化酶催化黄嘌呤降解会导致超氧阴离子、过氧化氢和羟基自由基的形成。在牛巴贝斯虫存在的情况下进行的降解对该寄生虫有毒性。添加ROI清除剂过氧化氢酶可部分逆转这种毒性。然而,直接添加H2O2几乎没有效果,这表明其他ROI产物发挥了作用。多胺氧化酶催化精胺降解以及直接添加丙烯醛均具有剂量依赖性毒性。最后,硝普钠或S-亚硝基-N-乙酰青霉胺自发产生一氧化氮也具有剂量依赖性毒性。这些数据使我们认为活化巨噬细胞在针对牛巴贝斯虫的初次免疫反应中发挥作用。