Protectin D1 mitigates acute lung inflammation in a murine model of acute lung injury

Abstract

Background: Acute lung injury (ALI) is a clinical condition characterized by lung inflammation following various injury and frequently associated severe morbidity and mortality. Recently, protectin D1 (PD1), a natural chemical mediator derived from docosahexaenoic acid, has been suggested to have a role in the resolution of inflammation. In this study, we investigated if the administration of PD1 could ameliorate acute lung inflammation using a murin model of acute lung injury. Methods: Lipopolysaccharide (LPS) was administered intratracheally in BALB/c mice to induce acute lung inflammation. Effects of the intravenous injection of PD1 one hour before LPS exposure were compared with sham-treated mice using the measurement of lung histology and inflammatory cell counts of bronchoalveolar lavage fluid (BALF) at 12 and 24 hours after LPS administration. Results: Compared with sham-treated mice, PD1-treated mice showed significant decrease in total inflammatory cell counts and neutrophil counts of BALF and lung histology. While there was no significant difference in the expression of cytokines related with lung inflammation, TUNEL stain of lung tissue and the measurement of Caspase-3 activity demonstrated the increased apoptosis of neutrophils in PD1-treated mice. Conclusion: PD1 diminished lung inflammation in a murine model of lung injury by the regulation of neutrophil apoptosis regardless of cytokine or chemokine expressions. These findings suggest that PD1 acts as an important counterregulatory role in lung inflammation