title: Airway purinergic responses in healthy, atopic nonasthmatic, and atopic asthmatic subjects exposed to ozone.
abstract: BACKGROUND
  Ozone exposure triggers airway inflammatory responses that may be influenced by biologically active purine metabolites.
  
  
  OBJECTIVE
  To examine the relationships between airway purine metabolites and established inflammatory markers of ozone exposure, and to determine if these relationships are altered in individuals with atopy or asthma.
  
  
  METHODS
  Mass spectrometry was utilized to measure concentrations of purine metabolites (adenosine monophosphate [AMP], adenosine, hypoxanthine, uric acid) and non-purine metabolites (taurine, urea, phenylalanine, tyrosine) in induced sputum obtained from 31 subjects with normal lung function (13 healthy controls, eight atopic nonasthmatics, and 10 atopic asthmatic [AA]) before and 4 h after ozone exposure.
  
  
  RESULTS
  At baseline, the purines AMP and hypoxanthine correlated with multiple inflammatory markers including neutrophil counts and the cytokines interleukin (IL)-6, IL-8, tumor necrosis factor alpha (TNF-α), and IL-1β (r ranged from 0.41 to 0.66, all P < 0.05). Following ozone exposure, these purines remained correlated with IL-6, IL-8, and TNF-α (r = 0.37-0.68). However, AMP and hypoxanthine increased significantly post ozone exposure in atopic nonasthmatics but not in AA. In contrast, the non-purine metabolite taurine correlated with baseline neutrophil counts (r = 0.56) and IL-6 (r = 0.53) and was elevated post-exposure in both atopic cohorts.
  
  
  CONCLUSIONS
  The purine metabolites AMP and hypoxanthine are correlated with multiple inflammatory markers at baseline and after ozone exposure. However, changes in these purine metabolites after ozone appear to differ from other inflammatory markers, with less response in AA relative to atopic nonasthmatics. Purine metabolites may play a role in the signaling responses to ozone, but these responses may be altered in subjects with asthma.
authors: Pediatric Pulmonology, University of North Carolina at Chapel Hill, 27517, USA. Charles_Esther@med.unc.edu
authors: Charles R
authors: CR
authors: Esther
authors: David B
authors: DB
authors: Peden
authors: Neil E
authors: NE
authors: Alexis
authors: Michelle L
authors: ML
authors: Hernandez
references: Am Rev Respir Dis. 1993 Jul;148(1):91-7
references: 8317821
references: J Allergy Clin Immunol. 2007 Sep;120(3):719-22
references: 17586033
references: Am J Physiol Lung Cell Mol Physiol. 2009 Jun;296(6):L987-93
references: 19304910
references: J Appl Physiol (1985). 1986 Apr;60(4):1321-6
references: 3084448
references: Eur Respir J. 2002 Dec;20(6):1393-8
references: 12503694
references: Science. 2006 Dec 15;314(5806):1792-5
references: 17170310
references: J Clin Invest. 2001 Apr;107(7):861-9
references: 11285305
references: Am Rev Respir Dis. 1976 May;113(5):587-600
references: 1267262
references: J Leukoc Biol. 1990 Aug;48(2):174-82
references: 2370482
references: Curr Med Chem. 2008;15(9):917-22
references: 18473799
references: Rapid Commun Mass Spectrom. 2008;22(5):701-5
references: 18257110
references: Proc Am Thorac Soc. 2007 Jul;4(3):240-6
references: 17607006
references: Curr Opin Pulm Med. 2006 Jan;12(1):54-9
references: 16357580
references: Br J Pharmacol. 2006 Jan;147 Suppl 1:S172-81
references: 16402102
references: Eur Respir J. 2005 May;25(5):873-8
references: 15863645
references: Clin Chem. 1982 Aug;28(8):1758-61
references: 7094296
references: J Immunol. 1996 Nov 15;157(10):4634-40
references: 8906843
references: J Allergy Clin Immunol. 2002 Mar;109(3):446-8
references: 11897989
references: Am J Respir Crit Care Med. 1997 Feb;155(2):479-84
references: 9032182
references: Am J Respir Crit Care Med. 1995 Dec;152(6 Pt 1):1910-6
references: 8520754
references: J Allergy Clin Immunol. 2010 Sep;126(3):537-44.e1
references: 20816188
references: J Allergy Clin Immunol. 2008 Sep;122(3):456-68; quiz 469-70
references: 18774381
references: Free Radic Biol Med. 2005 Jul 15;39(2):213-26
references: 15964513
references: Respir Med. 2010 Jan;104(1):29-33
references: 19646854
references: Pharmacol Ther. 2006 Nov;112(2):358-404
references: 16784779
references: Respirology. 2009 Jan;14(1):27-38
references: 19144046
references: Methods Mol Biol. 2006;341:73-87
references: 16799190
references: Am J Respir Cell Mol Biol. 1991 Jan;4(1):72-81
references: 1846079
references: Clin Exp Allergy. 2002 Mar;32(3):391-6
references: 11940069
references: J Immunol. 2008 Mar 15;180(6):4173-81
references: 18322229
references: Eur Respir J. 2008 May;31(5):949-56
references: 18256064
references: Pharmacol Rev. 2006 Mar;58(1):58-86
references: 16507883
references: J Exp Med. 1998 Oct 19;188(8):1433-43
references: 9782120
references: Am J Physiol. 1997 Mar;272(3 Pt 1):L504-11
references: 9124608
references: Am J Respir Crit Care Med. 2009 May 15;179(10):903-13
references: 19218193