Modulation of P2X7 purinergic receptor in macrophages by Leishmania amazonensis and its role in parasite elimination
Modulation of P2X7 purinergic receptor in macrophages by Leishmania amazonensis and its role in parasite elimination
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DOI：
10.1016/j.micinf.2009.05.001
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发表时间：
2009-09-01
影响因子：
5.8
通讯作者：
Rossi-Bergmann, Bartira
中科院分区：
文献类型：
--
作者：
Chaves, Suzana Passos;Torres-Santos, Eduardo Caio;Rossi-Bergmann, Bartira
嘌呤能 P2X(7) 受体是白细胞的一种膜蛋白，参与细胞内细菌（如衣原体和分枝杆菌）的清除。在这项工作中，我们研究了巨噬细胞 P2X(7)R 在原生动物寄生虫亚马逊利什曼原虫细胞内感染中的作用和调节。感染后，分离的小鼠巨噬细胞表现出 P2X(7)R 表达增强，并且对细胞外 ATP (ATPe) 诱导的孔开放的反应显着增强，荧光黄摄取增加就证明了这一点。这扩展到了体内情况，来自已建立的皮肤损伤的细胞比来自未感染小鼠的细胞对 ATPe 更敏感。受感染巨噬细胞的 ATP 处理可抑制寄生虫生长，而用氧化 ATP（P2X(7)R 的选择性拮抗剂）预处理可防止寄生虫生长。由于诱导一氧化氮产生或受感染巨噬细胞的细胞溶解，不太可能杀死寄生虫，因为这些功能不会因寄生虫有效的 ATPe 浓度而改变。直接药物效应也不同，因为 ATPe 增强了无菌寄生虫的生长。我们发现利什曼原虫感染使野生型巨噬细胞更容易发生 ATP 诱导的细胞凋亡，但 P2X(7)R 缺陷型巨噬细胞则不然。这些结果表明，亚马逊乳杆菌感染的巨噬细胞导致功能性P2X(7)R表达增强，与ATPe连接后，通过可能涉及宿主细胞凋亡的尚不清楚的机制有助于消除寄生虫。 (C) 2009 Elsevier Masson SAS。版权所有。
The purinergic P2X(7) receptor is a membrane protein of leucocytes involved in the clearance of intracellular bacteria such as Chlamydia and Mycobacterium. In this work, we investigated the role and modulation of macrophage P2X(7)R in intracellular infection with the protozoan parasite Leishmania amazonensis. Upon infection, isolated murine macrophages displayed enhanced expression of P2X(7)R and were significantly more responsive to extracellular ATP (ATPe)-induced pore opening, as demonstrated by the increased uptake of Lucifer Yellow. This was extended to the in vivo situation, where cells from established cutaneous lesions were more sensitive to ATPe than cells from uninfected mice. ATP treatment of infected macrophages inhibited parasite growth, and this was prevented by pre-treatment with oxidized ATP, a selective antagonist of P2X(7)R. Parasite killing was unlikely due to induction of nitric oxide production or cytolysis of infected macrophage, as those functions were unaltered with parasite-effective ATPe concentrations. A direct drug effect is also unlike, as ATPe enhanced axenic parasite growth. We found that leishmanial infection rendered wild-type but not P2X(7)R-deficient macrophages more prone to ATP-induced apoptosis. These results show that macrophage infection with L. amazonensis leads to enhanced expression of functional P2X(7)R, that upon ligation with ATPe helps in the elimination of the parasites by an as yet unclear mechanism possibly involving host cell apoptosis. (C) 2009 Elsevier Masson SAS. All rights reserved.