Chemokine (C-C motif) receptor-like 2 is not essential for lung injury, lung inflammation, or airway hyperresponsiveness induced by acute exposure to ozone

Farhan Malik, Kevin Ryan Cromar, Constance L. Atkins, Roger E. Price, William T. Jackson, Saad R. Siddiqu, Chantal Y. Spencer, Nicholas C. Mitchell, Ikram U. Haque, Richard A. Johnston

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article numbere13545
JournalPhysiological Reports
Volume5
Issue number24
DOIs
StatePublished - Dec 1 2017

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CCR Receptors
Ozone
Bronchoalveolar Lavage Fluid
Lung Injury
Pneumonia
Air
Lung
Genotype
Leukocyte Chemotaxis
Pathology
Air Pollutants
Chemokine Receptors
Mast Cells
Respiratory System
Inhalation
Chlorides
Neutrophils
Leukocytes
Epithelial Cells
Macrophages

Keywords

  • Chemerin
  • Cmklr1
  • CXCR2
  • Gpr1
  • Methacholine
  • Osteopontin

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Chemokine (C-C motif) receptor-like 2 is not essential for lung injury, lung inflammation, or airway hyperresponsiveness induced by acute exposure to ozone. / Malik, Farhan; Cromar, Kevin Ryan; Atkins, Constance L.; Price, Roger E.; Jackson, William T.; Siddiqu, Saad R.; Spencer, Chantal Y.; Mitchell, Nicholas C.; Haque, Ikram U.; Johnston, Richard A.

In: Physiological Reports, Vol. 5, No. 24, e13545, 01.12.2017.

Research output: Contribution to journalArticle

Malik, Farhan ; Cromar, Kevin Ryan ; Atkins, Constance L. ; Price, Roger E. ; Jackson, William T. ; Siddiqu, Saad R. ; Spencer, Chantal Y. ; Mitchell, Nicholas C. ; Haque, Ikram U. ; Johnston, Richard A. / Chemokine (C-C motif) receptor-like 2 is not essential for lung injury, lung inflammation, or airway hyperresponsiveness induced by acute exposure to ozone. In: Physiological Reports. 2017 ; Vol. 5, No. 24.
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abstract = "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.",
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