The P2X7 Receptor Contributes to the Development of the Exacerbated Inflammatory Response Associated with Sepsis
The P2X7 Receptor Contributes to the Development of the Exacerbated Inflammatory Response Associated with Sepsis
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DOI：
10.1159/000371388
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发表时间：
2015-01-01
影响因子：
5.3
通讯作者：
Coutinho-Silva, Robson
中科院分区：
文献类型：
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作者：
Santana, Patricia Texeira;Benjamim, Claudia Farias;Coutinho-Silva, Robson
背景：脓毒症与全世界重症监护病房的高死亡率相关，代表对感染的全身炎症反应。 P2X7 是一种离子型嘌呤受体，具有已知的促炎活性。在这里，我们研究了 P2X7 受体在盲肠结扎穿刺 (CLP) 诱导的脓毒症中的作用。方法：对野生型 (WT) 和 P2X7KO (P2X7 null) 小鼠进行 CLP，并监测其存活 7 天。 CLP 24小时后收集血液、腹膜冲洗液和肺部，用于测量细菌负荷、免疫细胞浸润、一氧化氮（NO）、细胞因子水平和腹膜细胞死亡，并评估肺损伤。结果：CLP 后 7 天，P2X7KO 小鼠的存活率显着提高（WT 动物为 60%，为 30%），炎症反应总体减弱，腹膜细胞募集减少，NO 和促炎细胞因子（IL-1α、IL-6、IL-12、IL-17 和 IL-4）水平没有或有限增加，腹膜细胞凋亡减少，肺部浸润和形态学不明显。变化。结论：我们的数据显示，P2X7 受体是脓毒症相关炎症反应发生所必需的，并支持 P2X7 受体是炎症性疾病有效治疗靶点的观点。 (C) 2015 S. Karger AG，巴塞尔
Background: Sepsis is associated with high mortality rates in intensive care units worldwide and represents a systemic inflammatory response to infection. P2X7 is an ionotropic purine receptor with known proinflammatory activity. Here, we investigated the role of the P2X7 receptor in sepsis induced by cecal ligation and puncture (CLP). Methods: Wildtype (WT) and P2X7KO (P2X7 null) mice were subjected to CLP and their survival was monitored for 7 days. Blood, peritoneal wash and lungs were collected 24 h after CLP and used to measure bacterial load, immune cell infiltration, nitric oxide (NO), cytokine levels, and peritoneal cell death and to assess lung injury. Results: P2X7KO mice showed significantly increased survival 7 days after CLP (30% compared to 60% in WT animals) accompanied by an overall attenuated inflammatory response, with decreased cell recruitment to the peritoneum, no or limited increases in the levels of NO and proinflammatory cytokines (IL-1 alpha, IL-6, IL-12, IL-17, and IL-4), reduced peritoneal cell apoptosis, and less pronounced lung infiltration and morphological changes. Conclusions: Our data show the P2X7 receptor is required for the development of the inflammatory response associated with sepsis and support the notion that P2X7 receptor is a valid therapeutic target against inflammatory diseases. (C) 2015 S. Karger AG, Basel