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Olfactory ensheathing cells: Nitric oxide production and innate immunity

机译:嗅鞘细胞:一氧化氮的产生和先天免疫

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摘要

Olfactory nerves extend from the nasal cavity to the central nervous system and provide therefore, a direct route for pathogenic infection of the brain. Since actual infection by this route remains relatively uncommon, powerful endogenous mechanisms for preventing microbial infection must exist, but these remain poorly understood. Our previous studies unexpectedly revealed that the unique glial cells that ensheath olfactory nerves, olfactory ensheathing cells (OECs), expressed components of the innate immune response. In this study, we show that OECs are able to detect and respond to bacterial challenge via the synthesis of nitric oxide. In vitro studies revealed that inducible nitric oxide synthase (iNOS) mRNA and protein were present in Escherichia coli- and Staphylococcus aureus-incubated OECs, but were barely detectable in untreated OECs. Neuronal NOS and endothelial NOS were not expressed by OECs pre- and post-bacterial incubation. Nuclear translocation of nuclear factor kappa B (NFjB), detectable in the majority of OECs 1 h following bacterial incubation, preceded iNOS induction which resulted in the production of nitric oxide. N ~G-methyl-L-arginine significantly attenuated nitric oxide (P < 0.001) and nitrite production (P < 0.001) by OECs. In rat olfactory mucosa which was compromised by irrigation with 0.17M zinc sulfate or 0.7% Triton X-100 to facilitate bacterial infiltration, OECs contributed to a robust synthesis of iNOS. These data strongly support the hypothesis that OECs are an essential component of the innate immune response against bacterial invasion of the central nervous system via olfactory nerves.
机译:嗅觉神经从鼻腔延伸到中枢神经系统,因此提供了脑部病原体感染的直接途径。由于通过这种途径进行的实际感染仍然相对罕见,因此必须存在防止微生物感染的强大内源性机制,但对这些机制的了解仍然很少。我们以前的研究出乎意料地揭示,包裹嗅神经的独特神经胶质细胞,嗅鞘细胞(OEC),表达了先天免疫反应的组成部分。在这项研究中,我们表明OEC能够通过一氧化氮的合成检测并应对细菌攻击。体外研究表明,在大肠杆菌和金黄色葡萄球菌培养的OEC中存在诱导型一氧化氮合酶(iNOS)mRNA和蛋白质,但在未经处理的OEC中几乎检测不到。细菌孵育前后,OEC均未表达神经元NOS和内皮NOS。在细菌培养1小时后的大多数OEC中可检测到的核因子kappa B(NFjB)的核易位先于iNOS诱导,导致一氧化氮的产生。 N〜G-甲基-L-精氨酸显着减弱了OEC产生的一氧化氮(P <0.001)和亚硝酸盐的产生(P <0.001)。在大鼠嗅觉粘膜中,通过用0.17M硫酸锌或0.7%Triton X-100冲洗以促进细菌渗透而受损,OEC促进了iNOS的合成。这些数据强烈支持以下假设:OEC是针对通过嗅觉神经侵袭中枢神经系统的细菌的先天免疫应答的重要组成部分。

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