Plasminogen activator inhibitor-1 does not contribute to the pulmonary pathology induced by acute exposure to ozone.
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 O3Given 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 O3To 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. O3significantly 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 O3exposure. 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.
Division of Critical Care Medicine, Department of Pediatrics, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, Texas.
Hamza S
HS
Elkhidir
Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, College of Medicine, Medical University of South Carolina, Charleston, South Carolina.
Jeremy B
JB
Richards
Department of Environmental Medicine, New York University School of Medicine, Tuxedo, New York.
Kevin R
KR
Cromar
Division of Nephrology, Department of Pediatrics, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, Texas.
Cynthia S
CS
Bell
Comparative Pathology Laboratory, Center for Comparative Medicine, Baylor College of Medicine, Houston, Texas.
Roger E
RE
Price
Division of Pulmonary Medicine, Department of Pediatrics, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, Texas.
Constance L
CL
Atkins
Section of Pediatric Pulmonology, Department of Pediatrics, Baylor College of Medicine, Houston, Texas.
Chantal Y
CY
Spencer
Division of Critical Care Medicine, Department of Pediatrics, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, Texas.
Farhan
F
Malik
Pediatric Research Center, Department of Pediatrics, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, Texas.
Amy L
AL
Alexander
Pediatric Research Center, Department of Pediatrics, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, Texas.
Katherine J
KJ
Cockerill
Division of Critical Care Medicine, Department of Pediatrics, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, Texas.
Ikram U
IU
Haque
Division of Critical Care Medicine, Department of Pediatrics, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, Texas Pediatric Research Center, Department of Pediatrics, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, Texas Department of Integrative Biology and Pharmacology, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, Texas richard.a.johnston@uth.tmc.edu.
Richard A
RA
Johnston
Airway hyperresponsiveness; epithelial cell; lung injury; macrophage inflammatory protein‐2; neutrophil
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