title: Sensing pulmonary oxidative stress by lung vagal afferents.
abstract: Oxidative stress in the bronchopulmonary airways can occur through a variety of inflammatory mechanisms and also following the inhalation of environmental pollutants. Oxidative stress causes cellular dysfunction and thus mammals (including humans) have developed mechanisms for detecting oxidative stress, such that defensive behavior and defensive biological mechanisms can be induced to lessen its potential damage. Vagal sensory nerves innervating the airways play a critical role in the detection of the microenvironment in the airways. Oxidative stress and associated compounds activate unmyelinated bronchopulmonary C-fibers, initiating action potentials in these nerves that conduct centrally to evoke unpleasant sensations (e.g. urge to cough, dyspnea, chest-tightness) and to stimulate/modulate reflexes (e.g. cough, bronchoconstriction, respiratory rate, inspiratory drive). This review will summarize the published evidence regarding the mechanisms by which oxidative stress, reactive oxygen species, environmental pollutants and lipid products of peroxidation activate bronchopulmonary C-fibers. Evidence suggests a key role for transient receptor potential ankyrin 1 (TRPA1), although transient receptor potential vanilloid 1 (TRPV1) and purinergic P2X channels may also play a role. Knowledge of these pathways greatly aids our understanding of the role of oxidative stress in health and disease and represents novel therapeutic targets for diseases of the airways.
authors: Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, FL 33612, United States. ttaylorc@health.usf.edu
authors: Thomas E
authors: TE
authors: Taylor-Clark
authors: Bradley J
authors: BJ
authors: Undem
references: COPD. 2010 Aug;7(4):291-306
references: 20673039
references: Toxicol Ind Health. 2008 Aug;24(7):447-90
references: 19028774
references: J Appl Physiol (1985). 1989 Oct;67(4):1535-41
references: 2793755
references: Nat Neurosci. 2008 Aug;11(8):883-7
references: 18587390
references: J Clin Invest. 2008 May;118(5):1899-910
references: 18398506
references: Thorax. 2009 Mar;64(3):197-202
references: 18988661
references: Respir Physiol. 1997 Jun;108(3):195-204
references: 9241688
references: Respir Physiol Neurobiol. 2009 May 30;167(1):26-35
references: 18586581
references: Am J Physiol Regul Integr Comp Physiol. 2002 Jul;283(1):R86-98
references: 12069934
references: Channels (Austin). 2008 Jul-Aug;2(4):287-98
references: 18769139
references: Cell. 2006 Mar 24;124(6):1269-82
references: 16564016
references: Free Radic Biol Med. 2008 May 1;44(9):1689-99
references: 18313407
references: Curr Opin Pulm Med. 2003 Mar;9(2):144-50
references: 12574695
references: J Clin Invest. 2008 Jul;118(7):2574-82
references: 18568077
references: FASEB J. 2009 Apr;23(4):1102-14
references: 19036859
references: Cell. 2003 Mar 21;112(6):819-29
references: 12654248
references: Appl Occup Environ Hyg. 2002 Dec;17(12):840-5
references: 12495594
references: Proc Natl Acad Sci U S A. 2002 Jul 23;99(15):10150-5
references: 12097645
references: Mol Pharmacol. 2008 Feb;73(2):274-81
references: 18000030
references: J Physiol. 2005 Jun 1;565(Pt 2):563-78
references: 15802291
references: Nat Rev Drug Discov. 2009 Jan;8(1):55-68
references: 19116627
references: Lung. 2010 Oct;188(5):409-14
references: 20526719
references: Antioxid Redox Signal. 2010 Jan;12(1):93-124
references: 19634987
references: Br J Pharmacol. 2009 Nov;158(6):1621-8
references: 19845671
references: Proc Am Thorac Soc. 2007 Jul;4(3):240-6
references: 17607006
references: Proc Natl Acad Sci U S A. 2009 Nov 24;106(47):20097-102
references: 19897733
references: Curr Biol. 2005 May 24;15(10):929-34
references: 15916949
references: Am Rev Respir Dis. 1975 Jun;111(6):763-73
references: 1137245
references: Clin Exp Pharmacol Physiol. 2010 Aug;37(8):870-2
references: 20374258
references: Rev Physiol Biochem Pharmacol. 1984;99:1-110
references: 6695127
references: Pharmacol Ther. 2006 Aug;111(2):476-94
references: 16458359
references: J Pediatr. 2009 Mar;154(3):401-8, 408.e1
references: 18950799
references: J Appl Physiol (1985). 2006 Sep;101(3):950-9
references: 16645193
references: J Neurosci. 2004 Dec 15;24(50):11253-63
references: 15601931
references: J Allergy Clin Immunol. 2010 Dec;126(6):1141-8.e7
references: 21051083
references: Am J Physiol Lung Cell Mol Physiol. 2008 Nov;295(5):L858-65
references: 18689601
references: Am J Respir Cell Mol Biol. 1993 Nov;9(5):568-72
references: 7692898
references: J Appl Physiol (1985). 1999 Nov;87(5):1877-86
references: 10562632
references: J Appl Physiol (1985). 1985 Apr;58(4):1080-4
references: 3157668
references: J Pharmacol Exp Ther. 2003 Mar;304(3):1275-9
references: 12604706
references: J Physiol. 2008 Mar 15;586(6):1595-604
references: 18218683
references: Am J Respir Cell Mol Biol. 2009 Jun;40(6):756-62
references: 19059884
references: Int J Biochem Cell Biol. 2007;39(1):44-84
references: 16978905
references: Toxicol Sci. 2008 Apr;102(2):328-36
references: 18184637
references: J Appl Physiol (1985). 2003 May;94(5):1987-98
references: 12524382
references: Mol Pharmacol. 2004 Dec;66(6):1525-35
references: 15331767
references: J Appl Physiol (1985). 1989 May;66(5):2032-8
references: 2568354
references: J Neurosci. 2008 Mar 5;28(10):2485-94
references: 18322093
references: Am J Physiol Lung Cell Mol Physiol. 2004 Mar;286(3):L563-72
references: 14633515
references: J Physiol. 2004 May 1;556(Pt 3):905-17
references: 14978204
references: Physiology (Bethesda). 2008 Dec;23:360-70
references: 19074743
references: Antioxid Redox Signal. 2009 Sep;11(9):2209-22
references: 19203223
references: Neuron. 2004 Mar 25;41(6):849-57
references: 15046718
references: J Pharmacol Exp Ther. 2002 Nov;303(2):716-22
references: 12388656
references: APMIS. 2007 Feb;115(2):81-103
references: 17295675
references: Proc Natl Acad Sci U S A. 2006 Dec 19;103(51):19564-8
references: 17164327
references: Neuropharmacology. 2009 Sep;57(4):456-62
references: 19555701
references: Toxicol Sci. 2005 Feb;83(2):380-7
references: 15548641
references: J Appl Physiol (1985). 1993 May;74(5):2345-52
references: 8335566
references: Nature. 1997 Oct 23;389(6653):816-24
references: 9349813
references: J Physiol. 2010 Feb 1;588(Pt 3):423-33
references: 20008466
references: Nature. 2004 Jan 15;427(6971):260-5
references: 14712238
references: Toxicol Appl Pharmacol. 2003 Jan 15;186(2):63-76
references: 12639498
references: Respir Med. 2009 Nov;103(11):1592-613
references: 19608395
references: J Neurosci. 2007 Oct 17;27(42):11412-5
references: 17942735
references: Nature. 2001 Jun 21;411(6840):957-62
references: 11418861
references: N Engl J Med. 1963 Feb 14;268:353-7
references: 14016203
references: Proc Natl Acad Sci U S A. 2009 Jun 2;106(22):9099-104
references: 19458046
references: Toxicol Appl Pharmacol. 1973 Feb;24(2):279-97
references: 4696311
references: Proc Am Thorac Soc. 2004;1(3):191-9
references: 16113434
references: Ther Adv Respir Dis. 2008 Aug;2(4):215-35
references: 19124374
references: Am J Respir Crit Care Med. 2009 Dec 1;180(11):1042-7
references: 19729665
references: Int Immunopharmacol. 2010 Dec;10(12):1514-9
references: 20840838
references: J Pain. 2008 May;9(5):463-72
references: 18359667
references: Curr Opin Pharmacol. 2002 Jun;2(3):220-8
references: 12020461
references: Respir Res. 2011 Feb 03;12:19
references: 21291525
references: Pulm Pharmacol Ther. 2007;20(4):355-64
references: 17137814
references: J Immunol. 2008 Sep 1;181(5):3540-8
references: 18714027
references: J Appl Physiol (1985). 1998 Oct;85(4):1509-15
references: 9760348
references: Nature. 2007 Feb 1;445(7127):541-5
references: 17237762
references: J Appl Physiol (1985). 2006 Aug;101(2):644-54
references: 16627682
references: Br J Pharmacol. 1993 Mar;108(3):646-50
references: 7682132
references: Toxicol Appl Pharmacol. 2003 Oct 1;192(1):21-35
references: 14554100
references: Nat Neurosci. 2008 Mar;11(3):255-61
references: 18297068
references: Respirology. 2003 Sep;8(3):291-301
references: 14528878
references: Proc Am Thorac Soc. 2010 Jul;7(4):257-63
references: 20601629
references: J Neurosci. 2009 Sep 30;29(39):12284-91
references: 19793987
references: J Pharmacol Exp Ther. 2001 Mar;296(3):1043-50
references: 11181939
references: J Appl Physiol (1985). 2003 Apr;94(4):1563-71
references: 12626476
references: Br J Pharmacol. 2008 Jul;154(6):1359-68
references: 18500362
references: Curr Drug Metab. 2006 Dec;7(8):853-72
references: 17168687
references: J Allergy Clin Immunol. 1998 Jun;101(6 Pt 1):732-40
references: 9648699
references: J Physiol. 2008 Jul 15;586(14):3447-59
references: 18499726
references: Eur Respir J. 1999 Oct;14(4):845-53
references: 10573232
references: J Appl Physiol (1985). 2010 May;108(5):1293-303
references: 20167675
references: J Appl Physiol Respir Environ Exerc Physiol. 1979 Jun;46(6):1108-14
references: 468632
references: Am J Physiol. 1995 Jan;268(1 Pt 1):L71-7
references: 7840231
references: J Appl Physiol (1985). 1993 May;74(5):2338-44
references: 8335565
references: J Neurochem. 2010 Jan;112(1):77-91
references: 19840221
references: Behav Brain Res. 2004 Aug 12;153(1):181-8
references: 15219719
references: Pulm Pharmacol. 1988;1(1):33-9
references: 2980286
references: Development. 2000 Jul;127(14):3045-56
references: 10862742
references: Circ Res. 1986 Apr;58(4):512-22
references: 3698217
references: Proc Natl Acad Sci U S A. 2007 Aug 14;104(33):13519-24
references: 17684094
references: J Appl Physiol (1985). 1994 May;76(5):1848-55
references: 8063640
references: Am J Respir Cell Mol Biol. 2008 Aug;39(2):198-207
references: 18367723
references: J Physiol. 2005 Apr 15;564(Pt 2):437-50
references: 15705651
references: Free Radic Biol Med. 1992;12(1):83-8
references: 1537573
references: J Appl Physiol (1985). 2009 Oct;107(4):1285-92
references: 19628725
references: J Pharmacol Exp Ther. 1998 May;285(2):602-7
references: 9580604
references: J Physiol. 2004 Feb 15;555(Pt 1):115-23
references: 14634201
references: J Allergy Clin Immunol. 1976 Jul;58(1 PT 1):89-100
references: 181412
references: Proc Natl Acad Sci U S A. 2007 Aug 14;104(33):13525-30
references: 17686976
references: Am J Physiol Regul Integr Comp Physiol. 2008 Nov;295(5):R1572-84
references: 18768768
references: J Pharmacol Exp Ther. 2011 Apr;337(1):117-24
references: 21205926
references: Mol Pharmacol. 2006 Jul;70(1):383-94
references: 16614139
references: Eur J Neurosci. 2008 Mar;27(5):1131-42
references: 18364033
references: J Physiol. 2010 Dec 1;588(Pt 23):4769-83
references: 20937710