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Induction of tumor necrosis factor by Legionella pneumophila.

机译:嗜肺军团菌诱导肿瘤坏死因子。

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Mice were inoculated with Legionella pneumophila via an intratracheal route to establish an experimental model of infection. Lung lavage fluid obtained from infected mice contained a cytolytic factor identified as tumor necrosis factor (TNF). Peak levels of TNF were produced at about 24 h postinfection and rapidly declined thereafter. Treatment of the mice with dextran sulfate before inoculation with the bacteria resulted in lowered amounts of TNF in the lung lavage fluid, suggesting that macrophages were responsible for production of the cytokine. Furthermore, cultures of adherent lung leukocytes and a macrophage cell line, PU 5-1.8, were stimulated to produce TNF by exposure to Legionella antigens. In addition, adherent lung leukocytes from Legionella-infected mice spontaneously released TNF into the culture supernatant. Inoculation of mice with saline or latex particles failed to induce TNF in vivo, indicating that bacterial antigens or products were the stimulating signals. Since there was no detectable TNF activity in sera at any time after intratracheal inoculation, TNF production appeared to be confined to the site of infection. Pretreatment of PU 5-1.8 cultures with gamma interferon, which was detected in the lung lavage fluid before TNF, resulted in augmented TNF production, suggesting cooperativity may exist between the two cytokines, either in the pathogenicity of the bacterium or in a possible immunomodulatory function of TNF and interferon during infection.
机译:通过气管内途径用肺炎军团菌接种小鼠以建立感染的实验模型。从感染小鼠获得的肺灌洗液中含有一种溶细胞因子,被鉴定为肿瘤坏死因子(TNF)。 TNF的峰值水平在感染后约24小时产生,此后迅速下降。在用细菌接种之前用硫酸葡聚糖处理小鼠,导致肺灌洗液中的TNF含量降低,表明巨噬细胞负责细胞因子的产生。此外,通过暴露于军团菌抗原刺激粘附的肺白细胞和巨噬细胞系PU 5-1.8的培养物产生TNF。此外,来自军团菌感染小鼠的粘附的肺白细胞自发地将TNF释放到培养上清液中。用盐水或乳胶颗粒接种小鼠无法在体内诱导TNF,表明细菌抗原或产物是刺激信号。由于在气管内接种后的任何时间血清中均未检测到TNF活性,因此TNF的产生似乎仅限于感染部位。在TNF之前在肺灌洗液中检测到用γ干扰素对PU 5-1.8培养物进行预处理,导致TNF产生增加,表明两种细胞因子之间可能存在协同作用,无论是在细菌的致病性方面,还是在可能的免疫调节功能方面感染期间TNF和干扰素的含量。

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