Lipidomic analysis of bronchoalveolar lavage from mice exposed to ozone

Exposure to ozone causes decrements in pulmonary function, a response
associated with alterations in lung lipids. Pulmonary lipid homeostasis is
dependent on the activity of peroxisome proliferator-activated receptor
gamma (PPARγ), a nuclear receptor that regulates lipid uptake and
catabolism by alveolar macrophages (AMs). Herein, we assessed the role of
PPARγ in ozone-induced dyslipidemia and aberrant lung function in mice.
Exposure of mice to ozone (0.8 ppm, 3 hr) resulted in a significant
reduction in lung hysteresivity at 72 hr post-exposure; this correlated
with increases in levels of total phospholipids, specifically cholesteryl
esters, ceramides, phosphatidylcholines, phosphorylethanolamines,
sphingomyelins, and di- and triacylglycerols in lung lining fluid. This
was accompanied by a reduction in relative surfactant protein-B (SP-B)
content, consistent with surfactant dysfunction. Administration of the
PPARγ agonist, rosiglitazone (5 mg/kg/day, i.p.) reduced total lung
lipids, increased relative amounts of SP-B, and normalized pulmonary
function in ozone-exposed mice. This was associated with increases in lung
macrophage expression of CD36, a scavenger receptor important in lipid
uptake and a transcriptional target of PPARγ. These findings highlight the
role of alveolar lipids as regulators of surfactant activity and pulmonary
function following ozone exposure and suggest that targeting lipid uptake
by lung macrophages may be an efficacious approach for treating altered
respiratory mechanics.