Inhalation of ozone (O3), 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 O3. 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 O3-induced lung pathology and that chemerin, a Ccrl2 ligand, is increased in bronchoalveolar lavage fluid (BALF) by O3, we hypothesized that Ccrl2 contributes to the development of lung injury, lung inflammation, and airway hyperresponsiveness induced by O3. 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-b-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 O3. In air-exposed mice, BALF chemerin was greater in Ccrl2-deficient as compared to wild-type mice. O3 increased BALF chemerin in mice of both genotypes, yet following O3 exposure, BALF chemerin was greater in Ccrl2-deficient as compared to wild-type mice. O3 increased indices of lung injury, lung inflammation, and airway responsiveness. Nevertheless, no indices were different between genotypes following O3 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 O3-induced lung pathology.
ASJC Scopus subject areas
- Physiology (medical)