Bandyopadhyay Jaya, Song Hyun-Ok, Park Byung-Jae, Singaravelu Gunasekaran, Sun Ju Lee, Ahnn Joohong, Cho Jeong Hoon
Department of Biotechnology, West Bengal University of Technology, Kolkata 700-064, India.
Biochem Biophys Res Commun. 2009 Dec 4;390(1):136-41. doi: 10.1016/j.bbrc.2009.09.082. Epub 2009 Sep 26.
Nramp1 (natural resistance-associated macrophage protein-1) is a functionally conserved iron-manganese transporter in macrophages. Manganese (Mn), a superoxide scavenger, is required in trace amounts and functions as a cofactor for most antioxidants. Three Nramp homologs, smf-1, smf-2, and smf-3, have been identified thus far in the nematode Caenorhabditis elegans. A GFP promoter assay revealed largely intestinal expression of the smf genes from early embryonic through adult stages. In addition, smf deletion mutants showed increased sensitivity to excess Mn and mild sensitivity to EDTA. Interestingly, these smf deletion mutants demonstrated hypersensitivity to the pathogen Staphylococcus aureus, an effect that was rescued by Mn feeding or knockdown of the Golgi calcium/manganese ATPase, pmr-1, indicating that Mn uptake is essential for the innate immune system. This reversal of pathogen sensitivity by Mn feeding suggests a protective and therapeutic role of Mn in pathogen evasion systems. We propose that the C. elegans intestinal lumen may mimic the mammalian macrophage phagosome and thus could be a simple model for studying Mn-mediated innate immunity.
Nramp1（天然抗性相关巨噬细胞蛋白1）是巨噬细胞中一种功能保守的铁锰转运蛋白。锰（Mn）作为一种超氧化物清除剂，需求量极少，并且作为大多数抗氧化剂的辅助因子发挥作用。迄今为止，在线虫秀丽隐杆线虫中已鉴定出三种Nramp同源物，即smf-1、smf-2和smf-3。绿色荧光蛋白（GFP）启动子分析表明，从胚胎早期到成虫阶段，smf基因主要在肠道中表达。此外，smf基因缺失突变体对过量锰的敏感性增加，对乙二胺四乙酸（EDTA）的敏感性轻度增加。有趣的是，这些smf基因缺失突变体对病原体金黄色葡萄球菌表现出超敏反应，通过喂食锰或敲低高尔基体钙/锰ATP酶pmr-1可以挽救这种效应，这表明锰的摄取对先天免疫系统至关重要。通过喂食锰来逆转病原体敏感性表明锰在病原体逃避系统中具有保护和治疗作用。我们提出，秀丽隐杆线虫的肠腔可能模拟哺乳动物巨噬细胞吞噬体，因此可能是研究锰介导的先天免疫的一个简单模型。
