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前列腺素 E 抑制中性粒细胞的杀伤能力。

Prostaglandin E Inhibits the Ability of Neutrophils to Kill .

机构信息

Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky College of Medicine, Lexington, KY 40536.

出版信息

J Immunol. 2019 Jun 15;202(12):3474-3482. doi: 10.4049/jimmunol.1900201. Epub 2019 May 6.

Abstract

PGE is a lipid-signaling molecule with complex roles in both homeostasis and inflammation. Depending on the cellular context, PGE may also suppress certain immune responses. In this study, we tested whether PGE could inhibit bacterial killing by polymorphonuclear neutrophils (PMN) using a mouse model of foodborne listeriosis. We found that PGE pretreatment decreased the ability of PMN harvested from the bone marrow of either BALB/cByJ or C57BL/6J mice to kill in vitro. PGE treatment slowed the migration of PMN toward the chemoattractant leukotriene B4, decreased uptake of by PMN, and inhibited the respiratory burst of PMN compared with vehicle-treated cells. When immune cells were isolated from the livers of infected mice and tested directly ex vivo for the presence of PGE, BALB/cByJ cells produced significantly more than C57BL/6J cells. Together, these data suggest that robust PGE production can suppress PMN effector functions, leading to decreased bacterial killing, which may contribute to the innate susceptibility of BALB/cByJ mice to infection with the facultative intracellular bacterial pathogen .

摘要

PGE 是一种脂质信号分子,在维持内环境稳定和炎症反应中发挥着复杂的作用。根据细胞的具体情况,PGE 也可能抑制某些免疫反应。在本研究中,我们使用食源性李斯特菌感染的小鼠模型,测试了 PGE 是否可以抑制多形核粒细胞(PMN)的杀菌能力。我们发现,PGE 预处理降低了从 BALB/cByJ 或 C57BL/6J 小鼠骨髓中采集的 PMN 在体外杀死细菌的能力。与用载体处理的细胞相比,PGE 处理减缓了 PMN 向趋化因子白三烯 B4 的迁移,减少了 PMN 对 的摄取,并抑制了 PMN 的呼吸爆发。当从感染小鼠的肝脏中分离免疫细胞并直接在体外测试是否存在 PGE 时,BALB/cByJ 细胞产生的 PGE 明显多于 C57BL/6J 细胞。综上所述,这些数据表明,强大的 PGE 产生可以抑制 PMN 的效应功能,导致细菌杀伤减少,这可能导致 BALB/cByJ 小鼠对兼性细胞内细菌病原体 的先天易感性增加。

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