MACROPHAGE NITRIC-OXIDE MEDIATES IMMUNOSUPPRESSION IN INFECTIOUS INFLAMMATION
MACROPHAGE NITRIC-OXIDE MEDIATES IMMUNOSUPPRESSION IN INFECTIOUS INFLAMMATION
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DOI：
10.1016/s0171-2985(11)80455-9
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发表时间：
1994-10-01
期刊：
影响因子：
2.8
通讯作者：
ALRAMADI, B
中科院分区：
文献类型：
--
作者：
EISENSTEIN, TK;HUANG, D;ALRAMADI, B
一种减毒活鼠伤寒沙门氏菌疫苗株在注射后7天诱导接种小鼠产生严重的免疫抑制。尽管巨噬细胞功能的许多参数上调，并对强毒沙门氏菌的攻击提供保护，但仍发生对有丝分裂原的免疫抑制和对绵羊红细胞的空斑形成反应的无能。研究表明，巨噬细胞一氧化氮介导免疫抑制，并可能也是疫苗的早发性保护能力。本文提出了一种“旁观者淋巴细胞自毒”模型来解释免疫抑制的机制。该模型提出，沙门氏菌激活的巨噬细胞产生一氧化氮，使附近的淋巴细胞失活，因此它们变得功能失调。N-G-单甲基-L-精氨酸抑制一氧化氮可逆转免疫抑制。有证据支持脾脏中的微生物负荷、产生的一氧化氮的程度和免疫抑制的程度之间的关系。建议这种由一氧化氮介导的微生物免疫抑制模型可推广用于理解由其他微生物（如分枝杆菌和麻疹病毒）诱导的免疫抑制和迟发型超敏反应的丧失。该模型可以解释在分枝杆菌感染期间的无反应性，特别是当抗酸杆菌的负担很高时，以及麻疹感染期间皮肤试验对结核菌素的反应性丧失。
A vaccine strain of live, attenuated Salmonella typhimurium induces profound immunosuppression in inoculated mice 7 days after injection. Immunosuppression to mitogens and inability to mount plaque-forming responses to sheep red blood cells occurs in spite of many parameters of upregulated macrophage function and protection against challenge with virulent Salmonella. Studies show that macrophage nitric oxide mediates the immunosuppression and presumably also the early-onset protective capacity of the vaccine. A model of ''bystander lymphocyte aurotoxicity'' is presented to explain the mechanism of immunosuppression. The model proposes that Salmonella-activated macrophages generate nitric oxide which inactivates lymphocytes in the vicinity, so they become dysfunctional. Inhibition of nitric oxide by N-G-monomethyl-L-arginine reverses immunosuppression. Evidence is presented that supports a relationship between the microbial burden in the spleen, the degree of nitric oxide produced, and the extent of immunosuppression. It is proposed that this model of microbial Immunosuppression mediated by nitric oxide is generalizable for understanding immunosuppression and loss of delayed-type hypersensitivity induced by other microbes, such as Mycobacteria and and measles virus. The model could account for anergy during mycobacterial infections, particularly when the burden of acid-fast bacilli is high, as well as loss of skin test reactivity to tuberculin during measles infection.