Platelet-activating factor increases reactive oxygen species-mediated microbicidal activity of human macrophages infected with Leishmania (Viannia) braziliensis
Platelet-activating factor increases reactive oxygen species-mediated microbicidal activity of human macrophages infected with Leishmania (Viannia) braziliensis
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DOI：
10.1093/femspd/ftx082
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发表时间：
2017-10-01
影响因子：
3.3
通讯作者：
Ribeiro-Dias, Fatima
中科院分区：
文献类型：
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作者：
Borges, Arissa Felipe;Morato, Camila Imai;Ribeiro-Dias, Fatima
血小板活化因子（PAF）是由巨噬细胞在炎症和感染过程中产生的。我们评估了PAF是否能够调节巴西利什曼原虫（巴西主要的利什曼原虫）对人巨噬细胞的感染。单核细胞衍生的巨噬细胞与前鞭毛体形式在不存在或存在外源性PAF的情况下孵育。我们观察到，感染前用低浓度PAF处理巨噬细胞可增加L。巴西。更重要的是，在感染前、感染中或感染后加入外源性PAF可以降低寄生率。此外，用PAF拮抗剂（PCA 4248）处理导致巨噬细胞感染以浓度依赖性方式显著增加，表明内源性PAF对控制L.巴西人感染在机制上，外源PAF增加了活性氧（ROS）的产生，而PCA 4248处理降低了L。巴西人感染当巨噬细胞被NADPH氧化酶抑制剂夹竹桃素处理时，外源性PAF的杀菌作用被取消。结果表明，PAF促进L. braziliensis，表明这种脂质介质可能与对照L.巴西人巨噬细胞感染。
Platelet-activating factor (PAF) is produced by macrophages during inflammation and infections. We evaluated whether PAF is able to modulate the infection of human macrophages by Leishmania braziliensis, the main Leishmania sp. in Brazil. Monocyte-derived macrophages were incubated with promastigote forms in absence or presence of exogenous PAF. We observed that the treatment of macrophages with low concentrations of PAF prior to infection increased the phagocytosis of L. braziliensis. More importantly, exogenous PAF reduced the parasitism when it was added before, during or after infection. In addition, treatment with a PAF antagonist (PCA 4248) resulted in a significant increase of macrophage infection in a concentration-dependent manner, suggesting that endogenous PAF is important to control L. braziliensis infection. Mechanistically, while exogenous PAF increased production of reactive oxygen species (ROS) treatment with PCA 4248 reduced oxidative burst during L. braziliensis infection. The microbicidal effects of exogenous PAF were abolished when macrophages were treated with apocynin, an NADPH oxidase inhibitor. The data show that PAF promotes the production of ROS induced by L. braziliensis, suggesting that this lipid mediator may be relevant to control L. braziliensis infection in human macrophages.