了解天然抗性相关巨噬细胞蛋白1的多种功能。
Understanding the multiple functions of Nramp1.
作者信息
Blackwell J M, Searle S, Goswami T, Miller E N
机构信息
Welcome Trust Centre for the Study of Molecular Mechanisms in Disease, Cambridge Institute for Medical Research, University of Cambridge School of Clinical Medicine, Wellcome Trust/MRC Building, Addenbrooke's Hospital, Hills Road, Cambridge, UK.
出版信息
Microbes Infect. 2000 Mar;2(3):317-21. doi: 10.1016/s1286-4579(00)00295-1.
Nramp1 regulates macrophage activation in infectious and autoimmune diseases. Nramp2 controls anaemia. Both are divalent cation (Fe(2+), Zn(2+), and Mn(2+)) transporters; Nramp2 a symporter of H(+) and metal ions, Nramp1 a H(+)/divalent cation antiporter. This provides a model for metal ion homeostasis in macrophages. Nramp2, localised to early endosomes, delivers extracellularly acquired divalent cations into the cytosol. Nramp1, localised to late endosomes/lysosomes, delivers divalent cations from the cytosol to phagolysosomes. Here, Fe(2+) generates antimicrobial hydroxyl radicals via the Fenton reaction. Zn(2+) and Mn(2+) may also influence endosomal metalloprotease activity and phagolysosome fusion. The many cellular functions dependent on metal ions as cofactors may explain the multiple pleiotropic effects of Nramp1, and its complex roles in infectious and autoimmune disease.
Nramp1在感染性疾病和自身免疫性疾病中调节巨噬细胞的激活。Nramp2控制贫血。二者均为二价阳离子（Fe(2+)、Zn(2+)和Mn(2+)）转运蛋白；Nramp2是H(+)和金属离子的同向转运体，Nramp1是H(+)/二价阳离子反向转运体。这为巨噬细胞中的金属离子稳态提供了一个模型。定位于早期内体的Nramp2将细胞外获取的二价阳离子转运到细胞质中。定位于晚期内体/溶酶体的Nramp1将二价阳离子从细胞质转运到吞噬溶酶体中。在这里，Fe(2+)通过芬顿反应产生抗菌羟基自由基。Zn(2+)和Mn(2+)也可能影响内体金属蛋白酶的活性和吞噬溶酶体的融合。许多依赖金属离子作为辅因子的细胞功能可能解释了Nramp1的多种多效性作用，以及它在感染性疾病和自身免疫性疾病中的复杂作用。
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