Deletion of P2X7 Attenuates Hyperoxia-induced Acute Lung Injury via Inflammasome Suppression
Digital Object Identifier (DOI)
Increasing evidence shows that hyperoxia is a serious complication of oxygen therapy in acutely ill patients that causes excessive production of free radicals leading to hyperoxia-induced acute lung injury (HALI). Our previous studies have shown that P2X7 receptor activation is required for inflammasome activation during HALI. However, the role of P2X7 in HALI is unclear. The main aim of this study was to determine the effect of P2X7 receptor gene deletion on HALI. Wild-type (WT) and P2X7 knockout (P2X7 KO) mice were exposed to 100% O2 for 72 h. P2X7 KO mice treated with hyperoxia had enhanced survival in 100% O2 compared with the WT mice. Hyperoxia-induced recruitment of inflammatory cells and elevation of IL-1β, TNF-α, monocyte chemoattractant protein-1, and IL-6 levels were attenuated in P2X7 KO mice. P2X7 deletion decreased lung edema and alveolar protein content, which are associated with enhanced alveolar fluid clearance. In addition, activation of the inflammasome was suppressed in P2X7-deficient alveolar macrophages and was associated with suppression of IL-1β release. Furthermore, P2X7-deficient alveolar macrophage in type II alveolar epithelial cells (AECs) coculture model abolished protein permeability across mouse type II AEC monolayers. Deletion of P2X7 does not lead to a decrease in epithelial sodium channel expression in cocultures of alveolar macrophages and type II AECs. Taken together, these findings show that deletion of P2X7 is a protective factor and therapeutic target for the amelioration of hyperoxia-induced lung injury.
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Citation / Publisher Attribution
American Journal of Physiology-Lung Cellular and Molecular Physiology, v. 310, issue 6, p. L572-L581
Scholar Commons Citation
Galam, Lakshmi; Rajan, Ashna; Failla, Athena; Soundararajan, Ramani; Lockey, Richard F.; and Kolliputi, Narasaiah, "Deletion of P2X7 Attenuates Hyperoxia-induced Acute Lung Injury via Inflammasome Suppression" (2016). Internal Medicine Faculty Publications. 230.