Hyperoxia exposure results in decreased expression of pro‐resolution receptor ALX/FPR2 (1153.12)

Abstract

Rationale: Endogenously produced polyunsaturated fatty acids (PUFAs) are key mediators of the anti‐inflammatory response following acute injury. PUFAs such as resolvins and lipoxins have demonstrated potent pro‐resolutionary effects in acute lung injury. These molecules have been shown to bind and exert their effects through G‐coupled protein receptor Lipoxin A4/formyl peptide receptor 2 (ALX/FPR2). Previous reports suggest that various septic or sterile insults lead to an increase in ALX/FPR2 expression; however, the response of ALX/FRP2 to oxidative stress has not been elucidated. In this study, we investigated the role of ALX/FPR2 in a murine mouse model of hyperoxic acute lung injury (HALI).Methods: C57BL/6 mice were exposed to hyperoxic (50, 75, or 95% O2) or normoxic (≍ 21% O2) conditions for 24, 48, or 72hrs. Following atmospheric treatment, mice were euthanized; bronchoalveolar lavage (BAL) fluid and lung tissue were collected for analysis. BAL fluid was used to assess alveolar protein leak. Lung tissue samples were used for histopathological analysis and to assess ALX/FPR2 protein and RNA expressiton following hyperoxia treatment.Results: Results reveal that hyperoxia exposure results in a significant decrease in ALX/FRP2 expression in comparison to normoxia treated controls. This decrease was dose dependent and reduction in ALX/FRP2 was evident in as little as 24hrs following hyperoxia exposure. For the first time, our results reveal a significant decrease in ALX/FRP2 expression which has not been shown in other forms of acute lung injury.Conclusion: While the production of PUFAs in HALI may be normal, their pro‐resolutionary effects may be dampened due to the decrease in receptor expression.Grant Funding Source: Supported By: NIH RO1 HL105932