Expression of the human NRAMP1 gene in professional primary phagocytes: Studies in blood cells and in HL-60 promyelocytic leukemia
Expression of the human NRAMP1 gene in professional primary phagocytes: Studies in blood cells and in HL-60 promyelocytic leukemia
复制标题
DOI：
10.1002/jlb.61.1.96
复制
发表时间：
1997-01-01
影响因子：
5.5
通讯作者：
Gros, P
中科院分区：
文献类型：
--
作者：
Cellier, M;Shustik, C;Gros, P
在小鼠中，天然耐药相关巨噬细胞蛋白1 （Nramp1）基因的突变破坏了对抗原性无关的细胞内寄生虫（如分枝杆菌、沙门氏菌和利什曼原虫）感染的抗性，Nramp1的表达仅限于网状内皮器官和外周血白细胞，在这些器官中，该蛋白可能作为一种尚未确定底物的膜转运蛋白起作用。为了鉴定表达NRAMP1 mRNA的人类血细胞类型，并确定这些细胞中NRAMP1的表达是如何被调节的，我们研究了分离的外周血白细胞和体外细胞系，我们观察到多态核白细胞（PMN）是NRAMP1表达的主要位点，其次是单核细胞（MN）。与血液MN相比，MN向组织（肺泡巨噬细胞）的迁移或体外成熟（长期培养）与NRAMP1的表达水平较高有关，Northern对模型培养细胞的RNA分析显示，在红细胞或淋巴细胞T或B谱系的转化细胞系以及单核/巨噬细胞途径的祖细胞（KG1, U937, THP1）和HL-60早幼粒细胞白血病中，NRAMP1的表达缺失。通过诱导il - 8- rb、c-FMS和CD14标记基因表达，诱导HL-60细胞向单核细胞/巨噬细胞（维生素D3、酚酯）或粒细胞途径（DMF DMSO）分化的同时，NRAMP1的表达也被强烈诱导。这些结果表明，NRAMP1的表达是髓系特异性的，是在PMN和MN成熟过程中获得的。讨论了NRAMP1可能是PMN和MN共同的吞噬体/内体装置的一个组成部分的可能性。
In the mouse, mutations at the natural resistance-associated macrophage protein 1 (Nramp1) gene abrogate resistance to infection with antigenically unrelated intracellular parasites such as Mycobacterium, Salmonella, and Leishmania, Nramp1 expression is restricted to reticuloendothelial organs and peripheral blood leukocytes, where the protein may function as a membrane transporter of an as yet to be identified substrate, To identify the human blood cell type(s) expressing NRAMP1 mRNA and determine how Nramp1 expression is regulated in these cells, we have examined separated populations of peripheral blood leukocytes and in vitro cell lines, We observed that polymorphonuclear leukocytes (PMN) are the major site of NRAMP1 expression, followed to a lesser degree by monocytes (MN), Migration of MN to tissues (alveolar macrophages) or maturation in vitro dong-term culture) was associated with a higher level of NRAMP1 expression compared with blood MN, Northern analyses of RNA from model cultured cells showed absence of NRAMP1 expression in transformed cell lines from either erythroid or lymphoid T or B lineages as well as progenitors of the monocyte/macrophage pathway (KG1, U937, THP1), and the HL-60 promyelocytic leukemia, Induction of differentiation of HL-60 cells toward either the monocyte/macrophage (vitamin D3, phorbol ester) or the granulocyte pathways (DMF DMSO), as measured by induction of IL8-Rb, c-FMS, and CD14 marker gene expression, was concomitant with a strong induction of NRAMP1 expression, These results suggest that NRAMP1 expression is specific to the myeloid Lineage and is acquired during the maturation of PMN and MN, The possibility that NRAMP1 may be a component of the phagosomal/endosomal apparatus common to PMN and MN is discussed.