Inhibition of virulent Mycobacterium tuberculosis by Bcg(r) and Bcg(s) macrophages correlates with nitric oxide production
Inhibition of virulent Mycobacterium tuberculosis by Bcg(r) and Bcg(s) macrophages correlates with nitric oxide production
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DOI：
10.1086/514154
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发表时间：
1997-12-01
影响因子：
6.4
通讯作者：
Garcia, LF
中科院分区：
文献类型：
--
作者：
Arias, M;Rojas, M;Garcia, LF
Nramp1 基因控制巨噬细胞对多种细胞内微生物的抗性或易感性；然而，关于其在强毒力结核分枝杆菌感染过程中的作用，存在相互矛盾的证据。一氧化氮 (NO) 是一种由巨噬细胞产生的有效抗分枝杆菌剂，也受到 Nramp1 的调节。比较了 B10R（耐药）和 B10S（敏感）鼠巨噬细胞抑制结核分枝杆菌 H37Rv 以及响应感染和干扰素-γ (IFN-γ) 产生 NO 的体外能力。受感染的B10R巨噬细胞抑制疾病、结核病引起的[H-3]尿嘧啶掺入，并产生比BIOS巨噬细胞更高量的NO。 IFN-γ增加了两种细胞的抑制活性。 N-G-单甲基-L-精氨酸 (N(G)MMA) 可逆转 IFN-γ 激活的 B10R 巨噬细胞对结核分枝杆菌的抑制作用。 L-精氨酸恢复了 NO 的产生，并增加了 IFN-γ 刺激的 N(G)MMA 处理的巨噬细胞的抗分枝杆菌活性。 Bcg/Nramp1 基因可能通过这些细胞产生 NO 的不同能力来调节巨噬细胞对强毒力结核分枝杆菌的耐药性或易感性。
The Nramp1 gene controls macrophage resistance or susceptibility to several intracellular microorganisms; however, there is conflicting evidence regarding its role during infection with virulent Mycobacterium tuberculosis. Nitric oxide (NO) is a potent antimycobacterial agent produced by macrophages, which is also regulated by Nramp1. The in vitro ability of B10R (resistant) and B10S (susceptible) murine macrophages to inhibit M. tuberculosis H37Rv and to produce NO in response to infection and interferon-gamma (IFN-gamma) was compared. Infected B10R macrophages inhibited [H-3]uracil incorporation by ill, tuberculosis and produced higher amounts of NO than did BIOS macrophages. IFN-gamma increased the inhibitory activity of both cells. Inhibition of M. tuberculosis by IFN-gamma-activated B10R macrophages was reversed by N-G-monomethyl-L-arginine (N(G)MMA). L-arginine restored NO production and increased the antimycobacterial activity by IFN-gamma-stimulated N(G)MMA-treated macrophages. The Bcg/Nramp1 gene may regulate macrophage resistance or susceptibility to virulent M. tuberculosis by a differential capability of these cells to produce NO.