20-hete mediates ozone-induced, neutrophil-independent airway hyper-responsiveness in mice20-hete介导臭氧感生,neutrophil-independent气道hyper-responsiveness老鼠.pdfVIP

20-HETE Mediates Ozone-Induced, Neutrophil- Independent Airway Hyper-Responsiveness in Mice 1 2 1 3,4 4 Philip R. Cooper , A. Clementina Mesaros , Jie Zhang , Peter Christmas , Christopher M. Stark , Karim 4 1 4 2 1,2 Douaidy , Michael A. Mittelman , Roy J. Soberman , Ian A. Blair , Reynold A. Panettieri, Jr. * 1 Department of Medicine and the Airways Biology Initiative, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of America, 2 Center of Excellence in Environmental Toxicology, Center for Cancer Pharmacology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America, 3 Biology Department, Radford University, Radford, Virginia, United States of America, 4 Harvard Medical School, Massachusetts General Hospital East, Charlestown, Massachusetts, United States of America Abstract Background: Ozone, a pollutant known to induce airway hyper-responsiveness (AHR), increases morbidity and mortality in patients with obstructive airway diseases and asthma. We postulate oxidized lipids mediate in vivo ozone-induced AHR in murine airways. Methodology/Principal Findings: Male BALB/c mice were exposed to ozone (3 or 6 ppm) or filtered air (controls) for 2 h. Precision cut lung slices (PCLS; 250 mm thickness) containing an intrapulmonary airway (,0.01 mm2 lumen area) were prepared immediately after exposure or 16 h later. After 24 h, airways were contracted to carbachol (CCh). Log EC50 and Emax values were then calculated by measuring