title: Lung inflammation and thrombogenic responses in a time course study of Csb mice exposed to ozone.
abstract: Ozone is a well-known oxidant air pollutant, inhalation of which can result in oxidative stress, and lead to pulmonary inflammation. The aim of this study was to evaluate the time-course events after a single ozone exposure in transcription-coupled repair defective Csb and wild type mice. Mice were exposed for 3 h to 2 ppm ozone and biological parameters related to oxidative stress and inflammation were examined in the lungs at 0, 4, 9, 24 and 48 h after exposure. In addition the procoagulant and thrombomodulin activities were explored by a combination of assays for tissue factor and thrombin generation. This study revealed a significant biological response to ozone, for both Csb and wild type mice. The onset of inflammation in Csb mice, as indicated by an increase in interleukin-6, tumor necrosis factor-alpha and total cell influx, occurred earlier compared with those seen in wild type mice. On the other hand, Csb mice showed a delayed antioxidant reaction compared with wild type mice. Both genotypes developed a procoagulant reaction characterized by a stably increased tissue factor activity and a progressive increase in thrombin generation after 2 days. These experiments have shown that ozone, a well-known toxic substance from the environment, induces not only inflammation, but also procoagulant reactions in the lungs of mice. These results have implications for understanding the systemic effects induced by oxidant air pollutants.
authors.affiliation: Centre for Environmental Health Research, National Institute for Public Health and the Environment, Bilthoven, the Netherlands.
authors.forename: Ingeborg M
authors.initials: IM
authors.lastname: Kooter
authors.forename: Kim
authors.initials: K
authors.lastname: Frederix
authors.forename: Henri M H
authors.initials: HM
authors.lastname: Spronk
authors.forename: A John F
authors.initials: AJ
authors.lastname: Boere
authors.forename: Daan L A C
authors.initials: DL
authors.lastname: Leseman
authors.forename: Harry
authors.initials: H
authors.lastname: van Steeg
authors.forename: Hugo
authors.initials: H
authors.lastname: ten Cate
authors.forename: Flemming R
authors.initials: FR
authors.lastname: Cassee
mesh_terms: D000395:Air Pollutants, Occupational / Q000633:toxicity*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002138:Calibration; D004260:DNA Repair / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size / Q000187:drug effects; D010083:Oxidants, Photochemical / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D010126:Ozone / Q000633:toxicity*; D011014:Pneumonia / Q000473:pathology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D013925:Thromboplastin / Q000378:metabolism; D013927:Thrombosis / Q000139:chemically induced* / Q000473:pathology*; D013997:Time Factors
chemical_list: D000395:Air Pollutants, Occupational; D010083:Oxidants, Photochemical; D012333:RNA, Messenger; D010126:Ozone; D013925:Thromboplastin