Pulmonary surfactant plays an important role in lung surface tension, defense against invading pathogens, and immune response. Furthermore, alveolar macrophages (AM) that comprise the front line of immune defense against inhaled microorganisms are covered by a layer of pulmonary fluid. Phosphatidylcholines (PCs), including unsaturated lipids such as 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), are the most prevalent phospholipids in pulmonary surfactant. POPC reacts with ozone to produce 1-palmitoyl-2-(9-oxo-nonanoyl)-sn-glycero-3-phosphocholine (PONPC), a soluble mediator that initiates an inflammatory reaction in the lungs. However, the modulatory effects of POPC and PONPC on biology and activity of AM remain inconclusive. The exposure of AM (cell line AMJ2-C11) to POPC and PONPC was not directly related to the production of inflammatory mediators. However, AM, pre-incubated with POPC or PONPC, showed enhanced response after lipopolysaccharide (LPS) stimulation, and increased the production of nitric oxide and cytokines. This phenomenon was also observed for classical-polarized macrophages (M1). This increment on the production of inflammatory mediators was not associated with macrophage polarization, but with up-regulation of Tlr4 and Myd88 gene expression, which was in accordance with the adaptation of immune cells. This observation was confirmed by the histone acetylation epigenetic pathway. In contrast to the priming effect of POPC on AM activity, a harmful immune response, induced on incubation with PONPC, improved prostaglandin E2 (PGE2) formation, resulting in diminished bacterial phagocytosis. Additionally, PONPC induced production of CXCL1/KC, which potentially mediates neutrophil recruitment and enhances tissue inflammation. These results disclosed another dynamic mechanism by which pulmonary surfactant lipids (natural or oxidized) primed macrophage activity, thus affecting lung host defense.

中文翻译：

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肺表面活性剂磷脂酰胆碱诱导肺泡巨噬细胞的免疫适应性。

肺表面活性剂在肺表面张力，防御入侵病原体和免疫反应中起着重要作用。此外，肺部巨噬细胞（AM）构成了针对吸入微生物的免疫防御前线，被一层肺液覆盖。磷脂酰胆碱（PCs）是肺表面活性剂中最常见的磷脂，包括不饱和脂质，例如1-棕榈酰基-2-油酰基-sn-甘油-3-磷酸胆碱（POPC）。POPC与臭氧反应生成1-棕榈酰-2-（9-氧代壬酸）-sn-甘油-3-磷酸胆碱（PONPC），一种可溶性介质，在肺中引发炎症反应。但是，POPC和PONPC对AM的生物学和活性的调节作用尚无定论。AM（细胞系AMJ2-C11）暴露于POPC和PONPC并不与炎症介质的产生直接相关。但是，用POPC或PONPC预孵育的AM在脂多糖（LPS）刺激后显示增强的反应，并增加了一氧化氮和细胞因子的产生。对于经典极化巨噬细胞（M1）也观察到了这种现象。炎症介质产生的这种增加与巨噬细胞极化无关，但与Tlr4和Myd88基因表达的上调有关，这与免疫细胞的适应性有关。该观察结果由组蛋白乙酰化表观遗传途径证实。与POPC对AM活性的引发作用相反，与PONPC一起孵育会诱导有害的免疫反应，从而改善前列腺素E2（PGE2）的形成，导致细菌吞噬作用减弱。此外，PONPC诱导了CXCL1 / KC的产生，它可能介导嗜中性白细胞募集并增强组织炎症。这些结果揭示了肺动力学表面活性剂脂质（天然或氧化的）引发巨噬细胞活性的另一种动力学机制，从而影响了肺宿主防御。