Garrido Damien, Chanteloup Nathalie K, Trotereau Angélina, Lion Adrien, Bailleul Geoffrey, Esnault Evelyne, Trapp Sascha, Quéré Pascale, Schouler Catherine, Guabiraba Rodrigo
ISP, INRA, Université François Rabelais de Tours, Nouzilly, France.
Front Vet Sci. 2017 Dec 18;4:226. doi: 10.3389/fvets.2017.00226. eCollection 2017.
Lipid mediators are known to play important roles in the onset and resolution phases of the inflammatory response in mammals. The phospholipid platelet-activating factor (PAF) is a pro-inflammatory lipid mediator which participates in vascular- and innate immunity-associated processes by increasing vascular permeability, by facilitating leukocyte adhesion to the endothelium, and by contributing to phagocyte activation. PAF exerts its function upon binding to its specific receptor, PAF receptor (PAFR), which is abundantly expressed in leukocytes and endothelial cells (ECs). In chickens, lipid mediators and their functions are still poorly characterized, and the role of PAF as an inflammatory mediator has not yet been investigated. In the present study we demonstrate that primary chicken macrophages express PAFR and lysophosphatidylcholine acyltransferase 2 (LPCAT2), the latter being essential to PAF biosynthesis during inflammation. Also, exogenous PAF treatment induces intracellular calcium increase, reactive oxygen species release, and increased phagocytosis by primary chicken macrophages in a PAFR-dependent manner. We also show that PAF contributes to the lipopolysaccharide (LPS)-induced pro-inflammatory response and boosts the macrophage response to LPS phosphatidylinositol 3-kinase/Akt- and calmodulin kinase II-mediated intracellular signaling pathways. Exogenous PAF treatment also increases avian pathogenic intracellular killing by chicken macrophages, and PAFR and LPCAT2 are upregulated in chicken lungs and liver during experimental pulmonary colibacillosis. Finally, exogenous PAF treatment increases cell permeability and upregulates the expression of genes coding for proteins involved in leukocyte adhesion to the endothelium in primary chicken endothelial cells (chAEC). In addition to these vascular phenomena, PAF boosts the chAEC inflammatory response to bacteria-associated molecular patterns in a PAFR-dependent manner. In conclusion, we identified PAF as an inflammation amplifier in chicken macrophages and ECs, which suggests that PAF could play important roles in the endothelium-innate immunity interface in birds during major bacterial infectious diseases such as colibacillosis.
已知脂质介质在哺乳动物炎症反应的起始和消退阶段发挥重要作用。磷脂血小板活化因子（PAF）是一种促炎脂质介质，它通过增加血管通透性、促进白细胞与内皮细胞黏附以及促进吞噬细胞活化，参与与血管和固有免疫相关的过程。PAF与它的特异性受体PAF受体（PAFR）结合后发挥功能，PAFR在白细胞和内皮细胞（ECs）中大量表达。在鸡中，脂质介质及其功能仍未得到充分表征，PAF作为炎症介质的作用尚未得到研究。在本研究中，我们证明原代鸡巨噬细胞表达PAFR和溶血磷脂酰胆碱酰基转移酶2（LPCAT2），后者在炎症期间对PAF生物合成至关重要。此外，外源性PAF处理以PAFR依赖的方式诱导原代鸡巨噬细胞内钙增加、活性氧释放和吞噬作用增强。我们还表明，PAF有助于脂多糖（LPS）诱导的促炎反应，并增强巨噬细胞对LPS的反应，通过磷脂酰肌醇3激酶/Akt和钙调蛋白激酶II介导的细胞内信号通路。外源性PAF处理还增加了鸡巨噬细胞对禽致病性细菌的细胞内杀伤，并且在实验性肺大肠杆菌病期间，鸡肺和肝脏中的PAFR和LPCAT2上调。最后，外源性PAF处理增加了原代鸡内皮细胞（chAEC）的细胞通透性，并上调了编码参与白细胞与内皮细胞黏附的蛋白质的基因表达。除了这些血管现象外，PAF以PAFR依赖的方式增强chAEC对细菌相关分子模式的炎症反应。总之，我们确定PAF是鸡巨噬细胞和ECs中的炎症放大器，这表明PAF在诸如大肠杆菌病等主要细菌感染性疾病期间，可能在鸟类的内皮细胞-固有免疫界面中发挥重要作用。
