ALX/FPR2 Contributes to Serum Amyloid A-Induced Lung Neutrophil Recruitment Following Acute Ozone Exposure.

Ozone (O) is a toxic air pollutant that causes pulmonary inflammation, neutrophil recruitment, and lung injury. Part of the inflammatory response to O includes altered expression of formyl peptide receptor 2 (ALX/FPR2), a G protein-coupled receptor expressed primarily in immune cells. ALX/FPR2 is considered either anti-inflammatory/proresolving or proinflammatory depending on its ligands, which include lipoxin A4 or serum amyloid A (SAA). While the anti-inflammatory/proresolving lipoxin A4 ligand has been well studied, there remains a significant knowledge gap in the interaction between proinflammatory SAA and ALX/FPR2. To date, SAA has been shown to increase neutrophil recruitment through ALX/FPR2 and is increased systemically after O exposure. However, it is unclear if pulmonary SAA signals through ALX/FPR2 during the O-induced inflammatory response. We hypothesized that ALX/FPR2-SAA signaling is required to initiate neutrophil recruitment to the lungs following O exposure. To test this hypothesis, ALX/FPR2 wild type (FPR2) or knockout (FPR2) mice were exposed to filtered air (FA) or 1 ppm O for 3 h. Pulmonary inflammation was assessed 6, 24, and 48 h following O exposure. FPR2 mice exhibited impaired neutrophil recruitment at 6 and 24 h after O exposure. In addition, FPR2 mouse pulmonary SAA expression was significantly increased after O exposure compared to FPR2 mice. FPR2 mice dosed with SAA via oropharyngeal aspiration had increased pulmonary neutrophils, while neutrophils were not increased in FPR2 mice. Taken together, these data indicate that ALX/FPR2 may contribute to SAA-induced pulmonary neutrophilia following O exposure.