Chemokine (C‐C Motif) Receptor‐Like 2 is not essential for lung injury, lung inflammation, or airway hyperresponsiveness induced by acute exposure to ozone

Abstract Inhalation of ozone (O 3 ), a gaseous air pollutant, causes lung injury, lung inflammation, and airway hyperresponsiveness. Macrophages, mast cells, and neutrophils contribute to one or more of these sequelae induced by O 3 . Furthermore, each of these aforementioned cells express chemokine (C‐C motif) receptor‐like 2 (Ccrl2), an atypical chemokine receptor that facilitates leukocyte chemotaxis. Given that Ccrl2 is expressed by cells essential to the development of O 3 ‐induced lung pathology and that chemerin, a Ccrl2 ligand, is increased in bronchoalveolar lavage fluid (BALF) by O 3 , we hypothesized that Ccrl2 contributes to the development of lung injury, lung inflammation, and airway hyperresponsiveness induced by O 3 . To that end, we measured indices of lung injury (BALF protein, BALF epithelial cells, and bronchiolar epithelial injury), lung inflammation (BALF cytokines and BALF leukocytes), and airway responsiveness to acetyl‐ β ‐methylcholine chloride (respiratory system resistance) in wild‐type and mice genetically deficient in Ccrl2 (Ccrl2‐deficient mice) 4 and/or 24 hours following cessation of acute exposure to either filtered room air (air) or O 3 . In air‐exposed mice, BALF chemerin was greater in Ccrl2‐deficient as compared to wild‐type mice. O 3 increased BALF chemerin in mice of both genotypes, yet following O 3 exposure, BALF chemerin was greater in Ccrl2‐deficient as compared to wild‐type mice. O 3 increased indices of lung injury, lung inflammation, and airway responsiveness. Nevertheless, no indices were different between genotypes following O 3 exposure. In conclusion, we demonstrate that Ccrl2 modulates chemerin levels in the epithelial lining fluid of the lungs but does not contribute to the development of O 3 ‐induced lung pathology.