Ozone (O3) is a criteria
air pollutant known to increase the morbidity and mortality of cardiopulmonary diseases. This occurs through a pulmonary inflammatory response characterized by increased recruitment of immune cells into the airspace, pro-inflammatory
cytokines, and pro-inflammatory
lipid mediators. Recent evidence has demonstrated sex-dependent differences in the O3-induced pulmonary inflammatory response. However, it is unknown if this dimorphic response is evident in pulmonary
lipid mediator metabolism. We hypothesized that there are sex-dependent differences in
lipid mediator production following acute O3 exposure. Male and female C57BL/6J mice were exposed to 1 part per million O3 for 3 h and were necropsied at 6 or 24 h following exposure. Lung lavage was collected for cell differential and total
protein analysis, and lung tissue was collected for
mRNA analysis, metabololipidomics, and immunohistochemistry. Compared with males, O3-exposed female mice had increases in airspace neutrophilia, neutrophil
chemokine mRNA, pro-inflammatory
eicosanoids such as
prostaglandin E2, and specialized pro-resolving mediators (SPMs), such as
resolvin D5 in lung tissue. Likewise, precursor
fatty acids (arachidonic and
docosahexaenoic acid; DHA) were increased in female lung tissue following O3 exposure compared with males. Experiments with ovariectomized females revealed that loss of ovarian
hormones exacerbates
pulmonary inflammation and injury. However,
eicosanoid and SPM production were not altered by
ovariectomy despite depleted pulmonary DHA concentrations. Taken together, these data indicate that O3 drives an increased pulmonary inflammatory and bioactive
lipid mediator response in females. Furthermore,
ovariectomy increases susceptibility to O3-induced
pulmonary inflammation and injury, as well as decreases pulmonary DHA concentrations.