Arginine homeostasis in J774.1 macrophages in the context of Mycobacterium bovis BCG infection
Arginine homeostasis in J774.1 macrophages in the context of Mycobacterium bovis BCG infection
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DOI：
10.1128/jb.01687-05
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发表时间：
2006-07-01
影响因子：
3.2
通讯作者：
Connell, Nancy D.
中科院分区：
文献类型：
--
作者：
Talaue, Meliza T.;Venketaraman, Vishwanath;Connell, Nancy D.
诱导型一氧化氮合酶和精氨酸酶对L-精氨酸的竞争导致了几种寄生虫和细菌感染的结果。然而，L精氨酸的获得不仅对宿主细胞重要，而且对细胞内病原体也很重要。在本研究中，我们观察到缺乏编码精氨酸通透酶的Rv0522基因的牛分枝杆菌AS-1对J774.1小鼠巨噬细胞的L-精氨酸代谢产生干扰。AS-1可诱导J774.1细胞摄取L精氨酸，而野生型卡介苗则不能。这种对L精氨酸摄取的增加不依赖于干扰素和脂多糖的激活，并且与MCAT1和MCAT2阳离子氨基酸转运基因的表达增加有关。AS-1感染后，静息状态下J774.1细胞的精氨酸酶活性也升高。存活研究表明，AS-1在静息的J774.1细胞中的存活情况好于卡介苗。L去甲丙氨酸和二氟甲基鸟氨酸分别抑制J774.1细胞内精氨酸酶和鸟氨酸脱羧酶活性，进一步促进AS-1细胞内生长。这些结果表明，J774.1巨噬细胞的精氨酸相关活性受到感染卡介苗株精氨酸转运能力的影响。Rv0522基因编码的精氨酸转运的丧失可能在AS-1的细胞内生长过程中诱导了其他阳离子氨基酸运输系统，使其能够在静止的巨噬细胞内更好地存活。
The competition for L-arginine between the inducible nitric oxide synthase and arginase contributes to the outcome of several parasitic and bacterial infections. The acquisition Of L-arginine, however, is important not only for the host cells but also for the intracellular pathogen. In this study we observe that strain AS-1, the Mycobacterium bovis BCG strain lacking the Rv0522 gene, which encodes an arginine permease, perturbs L-arginine metabolism in J774.1 murine macrophages. Infection with AS-1, but not with wild-type BCG, induced L-arginine uptake in J774.1 cells. This increase in L-arginine uptake was independent of activation with gamma interferon plus lipopolysaccharide and correlated with increased expression of the MCAT1 and MCAT2 cationic amino acid transport genes. AS-1 infection also enhanced arginase activity in resting J774.1 cells. Survival studies revealed that AS-1 survived better than BCG within resting J774.1 cells. Intracellular growth of AS-1 was further enhanced by inhibiting arginase and ornithine decarboxylase activities in J774.1 cells using L-norvaline and difluoromethylornithine treatment, respectively. These results suggest that the arginine-related activities of J774.1 macrophages are affected by the arginine transport capacity of the infecting BCG strain. The loss of Rv0522 gene-encoded arginine transport may have induced other cationic amino acid transport systems during intracellular growth of AS-1, allowing better survival within resting macrophages.