Specialized Pro-Resolving Mediators MaR1 and LXA4 Resolve Inflammation During Acute Chemical Lung Injury in the Absence of Neutrophils.

Gastric aspiration pneumonia involves chemical injury to the alveoli of the lungs with inflammation, tissue damage, and recruitment of polymorphonuclear leukocytes (PMNs). PMNs are also known to be involved in the production of specialized pro-resolving mediators (SPMs), small lipid molecules that contribute to the resolution of inflammation. This study aimed to identify target PMN-produced SPMs and interrogate their actions and potential use for therapeutic treatment after chemical injury. The data revealed that maresin 1 (MaR1), lipoxin A4, and 18-HEPE are produced after chemical injury in the lungs, and that exogenous treatment with these SPMs reduces the acute influx of PMNs into the airspace. In a chemical lung injury model in which neutropenic mice all die within 48 hours, treatment with MaR1 or LXA4 rescued survival of neutropenic mice to the levels of immunologically intact mice, and reduced CD11b expression, a proinflammatory marker, on recruited PMNs. Exogenous treatment with MaR1 or LXA4 reduced the concentration of proinflammatory cytokines TNF⍺, IL6, and MCP-1 in the airspace at 24 hours after injury. These data show that exogenous treatment with MaR1 or LXA4 ameliorates acute inflammation after chemical lung injury and contributes to survival of severe murine aspiration pneumonia in neutropenic animals. These data have implications for treatment of sterile lung injury in immunocompromised patients.