Chan J, Fujiwara T, Brennan P, McNeil M, Turco S J, Sibille J C, Snapper M, Aisen P, Bloom B R
Department of Microbiology, Albert Einstein College of Medicine, Bronx, NY 10461.
Proc Natl Acad Sci U S A. 1989 Apr;86(7):2453-7. doi: 10.1073/pnas.86.7.2453.
Two important pathogens of developing countries, Mycobacterium leprae, the etiologic agent of leprosy, and Leishmania donovani, the protozoal parasite that causes kalaazar, persist in the human host primarily in mononuclear phagocytes. The mechanisms by which they survive in these otherwise highly cytocidal cells are presently unknown. Since the best understood cytocidal mechanism of these cells is the oxygen-dependent system that provides lethal oxidants including the superoxide anion (O2-), hydrogen peroxide (H2O2), hydroxyl radical (OH), and singlet oxygen (1O2), we sought specific microbial products of these organisms that might enable them to elude oxidative cytocidal mechanisms. Phenolic glycolipid I of M. leprae and lipophosphoglycan of L. donovani are unique cell-wall-associated glycolipids produced in large amounts by the organisms. In this study, phenolic glycolipid I derivatives and lipophosphoglycan were examined for their ability to scavenge potentially cytocidal oxygen metabolites in vitro. Electron spin resonance and spin-trapping indicate that phenolic glycolipid I derivatives and lipophosphoglycan are highly effective in scavenging hydroxyl radicals and superoxide anions. The results suggest that complex glycolipids and carbohydrates of intracellular pathogens that can scavenge oxygen radicals may contribute to their pathogenicity and virulence.
发展中国家的两种重要病原体，麻风病的病原体麻风分枝杆菌，以及引起黑热病的原生动物寄生虫杜氏利什曼原虫，主要在单核吞噬细胞中寄生于人类宿主。目前尚不清楚它们在这些原本具有高度细胞杀伤作用的细胞中存活的机制。由于这些细胞最广为人知的细胞杀伤机制是依赖氧气的系统，该系统会产生包括超氧阴离子（O2-）、过氧化氢（H2O2）、羟基自由基（OH）和单线态氧（1O2）在内的致命氧化剂，因此我们寻找这些生物体可能使其能够避开氧化细胞杀伤机制的特定微生物产物。麻风分枝杆菌的酚糖脂I和杜氏利什曼原虫的脂磷酸聚糖是这些生物体大量产生的独特的与细胞壁相关的糖脂。在本研究中，检测了酚糖脂I衍生物和脂磷酸聚糖在体外清除潜在细胞杀伤性氧代谢产物的能力。电子自旋共振和自旋捕获表明，酚糖脂I衍生物和脂磷酸聚糖在清除羟基自由基和超氧阴离子方面非常有效。结果表明，能够清除氧自由基的细胞内病原体的复合糖脂和碳水化合物可能有助于其致病性和毒力。
