PMID- 20422032
OWN - NLM
STAT- MEDLINE
DCOM- 20110616
LR  - 20211020
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 5
IP  - 4
DP  - 2010 Apr 20
TI  - 20-HETE mediates ozone-induced, neutrophil-independent airway 
      hyper-responsiveness in mice.
PG  - e10235
LID - 10.1371/journal.pone.0010235 [doi]
LID - e10235
AB  - 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 microm thickness) containing an intrapulmonary airway ( approximately 
      0.01 mm(2) lumen area) were prepared immediately after exposure or 16 h later. 
      After 24 h, airways were contracted to carbachol (CCh). Log EC(50) and E(max) 
      values were then calculated by measuring the airway lumen area with respect to 
      baseline. In parallel studies, dexamethasone (2.5 mg/kg), or 1-aminobenzotriazol 
      (ABT) (50 mg/kg) were given intraperitoneal injection to naive mice 18 h prior to 
      ozone exposure. Indomethacin (10 mg/kg) was administered 2 h prior. Cell counts, 
      cytokine levels and liquid chromatography-mass spectrometry (LC-MS) for lipid 
      analysis were assessed in bronchoalveolar lavage (BAL) fluid from ozone exposed 
      and control mice. Ozone acutely induced AHR to CCh. Dexamethasone or indomethacin 
      had little effect on the ozone-induced AHR; while, ABT, a cytochrome P450 
      inhibitor, markedly attenuated airway sensitivity. BAL fluid from ozone exposed 
      animals, which did not contain an increase in neutrophils or interleukin (IL)-6 
      levels, increased airway sensitivity following in vitro incubation with a naive 
      PCLS. In parallel, significant increases in oxidized lipids were also identified 
      using LC-MS with increases of 20-HETE that were decreased following ABT 
      treatment. CONCLUSIONS/SIGNIFICANCE: These data show that ozone acutely induces 
      AHR to CCh independent of inflammation and is insensitive to steroid treatment or 
      cyclooxygenase (COX) inhibition. BAL fluid from ozone exposed mice mimicked the 
      effects of in vivo ozone exposure that were associated with marked increases in 
      oxidized lipids. 20-HETE plays a pivotal role in mediating acute ozone-induced 
      AHR.
FAU - Cooper, Philip R
AU  - Cooper PR
AD  - Department of Medicine and the Airways Biology Initiative, University of 
      Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of 
      America.
FAU - Mesaros, A Clementina
AU  - Mesaros AC
FAU - Zhang, Jie
AU  - Zhang J
FAU - Christmas, Peter
AU  - Christmas P
FAU - Stark, Christopher M
AU  - Stark CM
FAU - Douaidy, Karim
AU  - Douaidy K
FAU - Mittelman, Michael A
AU  - Mittelman MA
FAU - Soberman, Roy J
AU  - Soberman RJ
FAU - Blair, Ian A
AU  - Blair IA
FAU - Panettieri, Reynold A
AU  - Panettieri RA
LA  - eng
GR  - R01 DK074821/DK/NIDDK NIH HHS/United States
GR  - R01 AI-068871/AI/NIAID NIH HHS/United States
GR  - R01 RO1DK74821/DK/NIDDK NIH HHS/United States
GR  - P30 ES013508/ES/NIEHS NIH HHS/United States
GR  - R01 AI068871/AI/NIAID NIH HHS/United States
GR  - R01CA091016/CA/NCI NIH HHS/United States
GR  - P30ES013508/ES/NIEHS NIH HHS/United States
GR  - R01 CA091016/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20100420
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Hydroxyeicosatetraenoic Acids)
RN  - 0 (Triazoles)
RN  - 1614-12-6 (1-aminobenzotriazole)
RN  - 66H7ZZK23N (Ozone)
RN  - 79551-86-3 (20-hydroxy-5,8,11,14-eicosatetraenoic acid)
RN  - 8Y164V895Y (Carbachol)
SB  - IM
MH  - Animals
MH  - Bronchial Hyperreactivity
MH  - Carbachol/pharmacology
MH  - Hydroxyeicosatetraenoic Acids/*analysis/*immunology
MH  - Lipid Peroxidation
MH  - Male
MH  - Mass Spectrometry
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Neutrophils
MH  - Ozone/*pharmacology
MH  - Respiratory Hypersensitivity/*etiology
MH  - Triazoles/pharmacology
PMC - PMC2857875
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2010/04/28 06:00
MHDA- 2011/06/17 06:00
PMCR- 2010/04/20
CRDT- 2010/04/28 06:00
PHST- 2009/12/16 00:00 [received]
PHST- 2010/03/26 00:00 [accepted]
PHST- 2010/04/28 06:00 [entrez]
PHST- 2010/04/28 06:00 [pubmed]
PHST- 2011/06/17 06:00 [medline]
PHST- 2010/04/20 00:00 [pmc-release]
AID - 09-PONE-RA-15016R1 [pii]
AID - 10.1371/journal.pone.0010235 [doi]
PST - epublish
SO  - PLoS One. 2010 Apr 20;5(4):e10235. doi: 10.1371/journal.pone.0010235.