Leukotriene B4 Modulates P2X7 Receptor-Mediated Leishmania amazonensis Elimination in Murine Macrophages
Leukotriene B4 Modulates P2X7 Receptor-Mediated Leishmania amazonensis Elimination in Murine Macrophages
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DOI：
10.4049/jimmunol.1301058
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发表时间：
2014-05-15
影响因子：
4.4
通讯作者：
Coutinho-Silva, Robson
中科院分区：
文献类型：
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作者：
Chaves, Mariana M.;Marques-da-Silva, Camila;Coutinho-Silva, Robson
ATP是免疫系统中重要的信号分子，能够结合P2 X7嘌呤能受体。最近，我们的小组表明，ATP处理的巨噬细胞消除亚马逊利什曼原虫。据报道，白三烯B4（LTB 4）减少感染的巨噬细胞的寄生虫负荷。此外，已经证明P2 X7受体可以诱导PLA 2活化和花生四烯酸动员。基于这些发现，我们研究了LTB 4是否在P2 X7受体激活后产生，并检查了LTB 4是否调节寄生虫消除。使用缺乏P2 X7受体的巨噬细胞，我们观察到ATP不能减少L。亚马逊负载该结果表明P2 X7嘌呤能受体在寄生虫消除中的作用。此外，ATP足以诱导LTB 4从感染的对照巨噬细胞释放，但不能从缺乏P2 X7受体的巨噬细胞释放。此外，我们发现，ATP不能降低5-脂氧合酶（LO）缺陷的巨噬细胞的寄生负载。用5-LO抑制剂AA 861处理也削弱了ATP对寄生负载的作用。5-LO基因敲除小鼠巨噬细胞对L. p2 X7受体基因敲除小鼠巨噬细胞对L.当与离子霉素一起孵育时，最后，我们证明了在存在CP 105696（LTB 4高亲和力受体的拮抗剂）的情况下，ATP不能降低寄生虫负荷。这些结果表明，P2 X7受体激活导致LTB 4的形成，这是L.亚马逊消除
ATP is an important signaling molecule in the immune system, and it is able to bind the P2X7 purinergic receptor. Recently, our group showed that ATP-treated macrophages eliminate Leishmania amazonensis. It has been reported that leukotriene B4 (LTB4) reduces the parasitic load of infected macrophages. Additionally, it has been demonstrated that the P2X7 receptor can induce PLA2 activation and arachidonic acid mobilization. Based on these findings, we investigated whether LTB4 is produced upon P2X7 receptor activation and examined whether LTB4 modulates parasite elimination. Using macrophages lacking the P2X7 receptor, we observed that ATP was not able to reduce L. amazonensis load. This result suggests a role of the P2X7 purinergic receptor in parasite elimination. In addition, ATP was sufficient to induce LTB4 release from infected control macrophages but not from macrophages lacking the P2X7 receptor. Moreover, we found that ATP failed to decrease the parasitic load in 5-lipoxygenase (LO)-deficient macrophages. Treatment with the 5-LO inhibitor AA861 also impairs the ATP effect on parasitic loads. Furthermore, macrophages from 5-LO knockout mice eliminated L. amazonensis in the presence of exogenous LTB4, and macrophages obtained from P2X7 receptor knockout mice eliminated L. amazonensis when incubated with ionomycin. Finally, we demonstrated that in the presence of CP105696, an antagonist for LTB4 high-affinity receptor, ATP was not able to reduce parasitic load. These results indicate that P2X7 receptor activation leads to LTB4 formation, which is required for L. amazonensis elimination.