Plasminogen activator inhibitor-1 does not contribute to the pulmonary pathology induced by acute exposure to ozone

Hamza S. Elkhidir, Jeremy B. Richards, Kevin Ryan Cromar, Cynthia S. Bell, Roger E. Price, Constance L. Atkins, Chantal Y. Spencer, Farhan Malik, Amy L. Alexander, Katherine J. Cockerill, Ikram U. Haque, Richard A. Johnston

Research output: Contribution to journalArticle

Abstract

Expression of plasminogen activator inhibitor (PAI)-1, the major physiological inhibitor of fibrinolysis, is increased in the lung following inhalation of ozone (O3), a gaseous air pollutant. PAI-1 regulates expression of interleukin (IL)-6, keratinocyte chemoattractant (KC), and macrophage inflammatory protein (MIP)-2, which are cytokines that promote lung injury, pulmonary inflammation, and/or airway hyperresponsiveness following acute exposure to O3. Given these observations, we hypothesized that PAI-1 contributes to the severity of the aforementioned sequelae by regulating expression of IL-6, KC, and MIP-2 following acute exposure to O3. To test our hypothesis, wild-type mice and mice genetically deficient in PAI-1 (PAI-1-deficient mice) were acutely exposed to either filtered room air or O3 (2 ppm) for 3 h. Four and/or twenty-four hours following cessation of exposure, indices of lung injury [bronchoalveolar lavage fluid (BALF) protein and epithelial cells], pulmonary inflammation (BALF IL-6, KC, MIP-2, macrophages, and neutrophils), and airway responsiveness to aerosolized acetyl-β-methylcholine chloride (respiratory system resistance) were measured in wild-type and PAI-1-deficient mice. O3 significantly increased indices of lung injury, pulmonary inflammation, and airway responsiveness in wild-type and PAI-1-deficient mice. With the exception of MIP-2, which was significantly lower in PAI-1-deficient as compared to wild-type mice 24 h following cessation of exposure to O3, no other genotype-related differences occurred subsequent to O3 exposure. Thus, following acute exposure to O3, PAI-1 neither regulates pulmonary expression of IL-6 and KC nor functionally contributes to any of the pulmonary pathological sequelae that arise from the noxious effects of inhaled O3.

Original languageEnglish (US)
Article numbere12983
JournalPhysiological Reports
Volume4
Issue number18
DOIs
StatePublished - Sep 1 2016

Fingerprint

Ozone
Plasminogen Activator Inhibitor 1
Pathology
Lung
Chemokine CXCL2
Chemotactic Factors
Keratinocytes
Interleukin-6
Lung Injury
Pneumonia
Bronchoalveolar Lavage Fluid
Air Pollutants
Fibrinolysis
Respiratory System
Inhalation
Neutrophils
Epithelial Cells
Macrophages
Air
Genotype

Keywords

  • Airway hyperresponsiveness
  • epithelial cell
  • lung injury
  • macrophage inflammatory protein-2
  • neutrophil

ASJC Scopus subject areas

  • Physiology (medical)
  • Physiology

Cite this

Elkhidir, H. S., Richards, J. B., Cromar, K. R., Bell, C. S., Price, R. E., Atkins, C. L., ... Johnston, R. A. (2016). Plasminogen activator inhibitor-1 does not contribute to the pulmonary pathology induced by acute exposure to ozone. Physiological Reports, 4(18), [e12983]. https://doi.org/10.14814/phy2.12983

Plasminogen activator inhibitor-1 does not contribute to the pulmonary pathology induced by acute exposure to ozone. / Elkhidir, Hamza S.; Richards, Jeremy B.; Cromar, Kevin Ryan; Bell, Cynthia S.; Price, Roger E.; Atkins, Constance L.; Spencer, Chantal Y.; Malik, Farhan; Alexander, Amy L.; Cockerill, Katherine J.; Haque, Ikram U.; Johnston, Richard A.

In: Physiological Reports, Vol. 4, No. 18, e12983, 01.09.2016.

Research output: Contribution to journalArticle

Elkhidir, HS, Richards, JB, Cromar, KR, Bell, CS, Price, RE, Atkins, CL, Spencer, CY, Malik, F, Alexander, AL, Cockerill, KJ, Haque, IU & Johnston, RA 2016, 'Plasminogen activator inhibitor-1 does not contribute to the pulmonary pathology induced by acute exposure to ozone', Physiological Reports, vol. 4, no. 18, e12983. https://doi.org/10.14814/phy2.12983
Elkhidir, Hamza S. ; Richards, Jeremy B. ; Cromar, Kevin Ryan ; Bell, Cynthia S. ; Price, Roger E. ; Atkins, Constance L. ; Spencer, Chantal Y. ; Malik, Farhan ; Alexander, Amy L. ; Cockerill, Katherine J. ; Haque, Ikram U. ; Johnston, Richard A. / Plasminogen activator inhibitor-1 does not contribute to the pulmonary pathology induced by acute exposure to ozone. In: Physiological Reports. 2016 ; Vol. 4, No. 18.
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abstract = "Expression of plasminogen activator inhibitor (PAI)-1, the major physiological inhibitor of fibrinolysis, is increased in the lung following inhalation of ozone (O3), a gaseous air pollutant. PAI-1 regulates expression of interleukin (IL)-6, keratinocyte chemoattractant (KC), and macrophage inflammatory protein (MIP)-2, which are cytokines that promote lung injury, pulmonary inflammation, and/or airway hyperresponsiveness following acute exposure to O3. Given these observations, we hypothesized that PAI-1 contributes to the severity of the aforementioned sequelae by regulating expression of IL-6, KC, and MIP-2 following acute exposure to O3. To test our hypothesis, wild-type mice and mice genetically deficient in PAI-1 (PAI-1-deficient mice) were acutely exposed to either filtered room air or O3 (2 ppm) for 3 h. Four and/or twenty-four hours following cessation of exposure, indices of lung injury [bronchoalveolar lavage fluid (BALF) protein and epithelial cells], pulmonary inflammation (BALF IL-6, KC, MIP-2, macrophages, and neutrophils), and airway responsiveness to aerosolized acetyl-β-methylcholine chloride (respiratory system resistance) were measured in wild-type and PAI-1-deficient mice. O3 significantly increased indices of lung injury, pulmonary inflammation, and airway responsiveness in wild-type and PAI-1-deficient mice. With the exception of MIP-2, which was significantly lower in PAI-1-deficient as compared to wild-type mice 24 h following cessation of exposure to O3, no other genotype-related differences occurred subsequent to O3 exposure. Thus, following acute exposure to O3, PAI-1 neither regulates pulmonary expression of IL-6 and KC nor functionally contributes to any of the pulmonary pathological sequelae that arise from the noxious effects of inhaled O3.",
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