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Supplementary Material for: The P2X7 Receptor Contributes to the Development of the Exacerbated Inflammatory Response Associated with Sepsis
<p><b><i>Background:</i></b> 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). <b><i>Methods:</i></b> 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. <b><i>Results:</i></b> 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. <b><i>Conclusions:</i></b>
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.</p