The P2X7 Receptor Contributes to the Development of the Exacerbated Inflammatory Response Associated with Sepsis

Autor: Claudia F. Benjamim, Patricia Texeira Santana, Camila Guerra Martinez, Eleonora Kurtenbach, Christina Maeda Takiya, Robson Coutinho-Silva
Rok vydání: 2015
Předmět:
Zdroj: Journal of Innate Immunity. 7:417-427
ISSN: 1662-8128
1662-811X
DOI: 10.1159/000371388
Popis: 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: Wild-type (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-1β, 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.
Databáze: OpenAIRE
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