Pulmonary Inflammation Induced by Subacute Ozone Is Augmented in Adiponectin-Deficient Mice: Role of IL-17A

Abstract

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 parts per million) exposure to ozone, adiponectin-deficient (Adipo^−/−) and wild-type mice were exposed to ozone or to room air. In wild-type 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, keratinocyte-derived chemokine, LPS-induced CXC chemokine, and G-CSF were augmented in Adipo^−/− versus wild-type mice. Ozone also increased IL-17A mRNA expression to a greater extent in Adipo^−/− versus wild-type mice. Moreover, compared with control Ab, anti–IL-17A Ab attenuated ozone-induced increases in BAL neutrophils and G-CSF in Adipo^−/− but not in wild-type 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 wild-type 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.