Hyaluronan Directs Alveolar Type II Cell Response to Acute Ozone Exposure in Mice.

Becoming more frequent because of climate change, ozone (O3) exposures can cause lung injury. Alveolar type 2 (AT2) cells and hyaluronan (HA), a matrix component, are critical to repairing lung injury and restoring homeostasis. Here, we define the impact of HA on AT2 cells after acute O3 exposure. C57BL/6J mice were exposed to filtered air or O3 (2 ppm) for 3 hours. HA was measured in BAL and lung tissue; HAS (HA synthase) 1, 2, and 3 and HYAL (hyaluronidase) 1, 2, and 3 mRNA were measured in lung tissue and BAL cells. At 48 to 72 hours after O3 exposure, HA increased in BAL fluid by ELISA and lung tissue by immunohistochemistry, with new HA deposition localized to the alveolar ducts. This was associated with increased whole-lung HAS2 mRNA expression. Using an AT2 lineage reporter (Sftpc-CreER;Rosa-Tm) mouse strain, we noted that proliferating AT2 cells colocalized with O3-induced HA deposition in the alveolar duct region. In addition, AT2-to-AT1 cell differentiation after O3 was noted. To determine whether O3-induced HA alters AT2 cell function, we inhibited HA-AT2 interaction with a synthetic inhibitor (Pep-1), which diminished AT2 proliferation. Mice treated with Pep-1 after O3 exposure demonstrated increased BAL albumin concentration compared with filtered air exposure, suggesting that inhibition of HA-AT2 cell interactions resulted in persistent alveolar-capillary permeability and diminished resolution of O3-induced lung injury. Overall, the findings suggest that HA increases in the alveolar duct after acute O3 exposure and that HA-AT2 cell interactions are required for resolution of acute O3-induced lung injury.

Duke Scholars

Author Christina Eleanor Barkauskas Medicine, Pulmonary, Allergy, and Critical Care Medicine

Author Robert Matthew Tighe Medicine, Pulmonary, Allergy, and Critical Care Medicine

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