Pulmonary inflammation induced by subacute ozone is augmented in adiponectin deficient mice: role of IL-17A

摘要

Pulmonary responses to ozone, a common air pollutant, are augmented in obese individuals. Adiponectin, an adipose derived hormone that declines in obesity, has regulatory effects on the immune system. To determine the role of adiponectin in the pulmonary inflammation induced by extended (48–72 h) low dose (0.3 ppm) exposure to ozone, adiponectin deficient (Adipo^−/−) and wildtype mice were exposed to ozone or to room air. In wildtype mice, ozone exposure increased total bronchoalveolar lavage (BAL) adiponectin. Ozone induced lung inflammation, including increases in BAL neutrophils, protein (an index of lung injury), IL-6, KC, LIX and G-CSF were augmented in Adipo^−/− versus wildtype mice. Ozone also increased IL-17A mRNA expression to a greater extent in Adipo^−/− versus wildtype mice. Moreover, compared to control antibody, anti-IL-17A antibody attenuated ozone-induced increases in BAL neutrophils and G-CSF in Adipo^−/− but not in wildtype mice, suggesting that IL-17A, by promoting G-CSF release, contributed to augmented neutrophilia in Adipo^−/− mice. Flow-cytometric analysis of lung cells revealed that the number of CD45⁺/F4/80⁺/IL-17A⁺ macrophages and γδ T cells expressing IL-17A increased after ozone exposure in wildtype mice, and further increased in Adipo^−/− mice. The IL-17⁺ macrophages were CD11c⁻ (interstitial macrophages), whereas CD11c⁺ macrophages (alveolar macrophages) did not express IL-17A. Taken together, the data are consistent with the hypothesis that adiponectin protects against neutrophil recruitment induced by extended, low dose ozone exposure by inhibiting the induction and/or recruitment of IL-17A in interstitial macrophages and/or γδ T cells.