Release of nitric oxide during the T cell-independent pathway of macrophage activation. Its role in resistance to Listeria monocytogenes.
Release of nitric oxide during the T cell-independent pathway of macrophage activation. Its role in resistance to Listeria monocytogenes.
复制标题
DOI：
10.4049/jimmunol.150.3.888
复制
发表时间：
1993-02
影响因子：
4.4
通讯作者：
K. Beckerman;H. W. Rogers;J. A. Corbett;Robert D. Schreiber;M. L. McDaniel;Emil R. Unanue
中科院分区：
文献类型：
--
作者：
K. Beckerman;H. W. Rogers;J. A. Corbett;Robert D. Schreiber;M. L. McDaniel;Emil R. Unanue
免疫缺陷小鼠对单核细胞增生李斯特菌 (LM) 感染具有显着的抵抗力。我们研究了一氧化氮 (NO.) 在 LM 的 CB-17/lcr SCID (SCID) 反应中所起的作用。 SCID 脾细胞产生大量 NO。 （通过亚硝酸盐形成测量）在存在热灭活 LM 的情况下孵育时。不。产生依赖于 SCID NK 细胞释放的 IFN-γ。直接测试时，巨噬细胞响应 LM 产生大量亚硝酸盐，但仅限于存在 IFN-γ 的情况下。生产NO。 LM 诱导的细胞因子不受 TNF 或 IL-1 中和抗体的影响。生产NO。添加两种 NO.合酶抑制剂（NG-单甲基精氨酸或氨基胍）中的任何一种均可抑制该酶的活性。在不同的情况下，被 TNF 和李斯特菌产品刺激释放 IFN-γ 的 NK 细胞不会产生 NO。用 IFN-γ 培养的巨噬细胞杀死了活的 LM。氨基胍显着抑制了 LM 杀伤力的增加。在体内，给予氨基胍会导致 LM 感染的 SCID 或免疫活性对照小鼠的死亡率和脾脏细菌负荷显着增加。我们的结论是NO。正如在 SCID 小鼠中所研究的那样，NO. 是 T 细胞独立的 LM 天然抗性的关键效应分子，并且 NO. 介导的反应对于 SCID 和免疫活性宿主在 LM 感染后生存至关重要。
Immunodeficient mice are remarkably resistant to Listeria monocytogenes (LM) infection. We examined the role that nitric oxide (NO.) plays in the CB-17/lcr SCID (SCID) response to LM. SCID spleen cells produced large quantities of NO. (as measured by nitrite formation) when incubated in the presence of heat-killed LM. NO. production was dependent on the release of IFN-gamma by the SCID NK cells. When tested directly, macrophages produced large quantities of nitrite in response to LM, but only in the presence of IFN-gamma. The production of NO. induced by LM was not affected by neutralizing antibodies to TNF or IL-1. The production of NO. was inhibited by addition of either of two inhibitors of NO.synthase, NG-monomethyl arginine, or aminoguanidine. In a different situation, NK cells that were stimulated by TNF and Listeria products to release IFN-gamma did not produce NO.. Macrophages cultured with IFN-gamma killed live LM. This increased killing of LM was significantly inhibited by amino-guanidine. In vivo, administration of aminoguanidine resulted in a marked increase in the mortality and spleen bacterial loads of LM-infected SCID or immunocompetent control mice. We conclude that NO. is a critical effector molecule of T cell-independent natural resistance to LM as studied in the SCID mouse, and that the NO.-mediated response is essential for both SCID and immunocompetent host to survive after LM infection.