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Respiratory Research
Published in: Respiratory Research 1/2009

Open Access 01-12-2009 | Research

Disparate oxidant gene expression of airway epithelium compared to alveolar macrophages in smokers

Published in: Respiratory Research | Issue 1/2009

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Abstract

Background

The small airway epithelium and alveolar macrophages are exposed to oxidants in cigarette smoke leading to epithelial dysfunction and macrophage activation. In this context, we asked: what is the transcriptome of oxidant-related genes in small airway epithelium and alveolar macrophages, and does their response differ substantially to inhaled cigarette smoke?

Methods

Using microarray analysis, with TaqMan RT-PCR confirmation, we assessed oxidant-related gene expression in small airway epithelium and alveolar macrophages from the same healthy nonsmoker and smoker individuals.

Results

Of 155 genes surveyed, 87 (56%) were expressed in both cell populations in nonsmokers, with higher expression in alveolar macrophages (43%) compared to airway epithelium (24%). In smokers, there were 15 genes (10%) up-regulated and 7 genes (5%) down-regulated in airway epithelium, but only 3 (2%) up-regulated and 2 (1%) down-regulated in alveolar macrophages. Pathway analysis of airway epithelium showed oxidant pathways dominated, but in alveolar macrophages immune pathways dominated.

Conclusion

Thus, the response of different cell-types with an identical genome exposed to the same stress of smoking is different; responses of alveolar macrophages are more subdued than those of airway epithelium. These findings are consistent with the observation that, while the small airway epithelium is vulnerable, alveolar macrophages are not "diseased" in response to smoking.

Trial Registration

ClinicalTrials.gov ID: NCT00224185 and NCT00224198
Appendix
Available only for authorised users
Literature
1.
Halliwell B: Reactive oxygen species in living systems: source, biochemistry, and role in human disease. Am J Med 1991, 91:14S-22S.CrossRefPubMed
2.
3.
Pryor WA, Stone K: Oxidants in cigarette smoke. Radicals, hydrogen peroxide, peroxynitrate, and peroxynitrite. Ann N Y Acad Sci 1993, 686:12–27.CrossRefPubMed
4.
Wright DT, Cohn LA, Li H, Fischer B, Li CM, Adler KB: Interactions of oxygen radicals with airway epithelium. Environ Health Perspect 1994,102(Suppl 10):85–90.CrossRefPubMedPubMedCentral
5.
Foronjy R, D'Armiento J: The effect of cigarette smoke-derived oxideants on the inflammatory response of the lung. Clin Appl Immunol Rev 2006, 6:53–72.CrossRefPubMedPubMedCentral
6.
Davis WB, Pacht ER: Extracellular antioxidant defenses. In The Lung: Sciencetific Foundations. Second edition. Edited by: Crystal RG, West JB, Weibel ER, Barnes PJ. Philadelphia: Lippinott-Raven; 1997:2271–2278.
7.
Repine JE, Heffiner JE: Lung antioxidents. In The Lung: Scientific Foundations. Second edition. Edited by: Crystal RG, West JB, Weibel ER, Barnes PJ. Philadelphia: Lippincott-Raven; 1997:2259–2269.
8.
Comhair SA, Erzurum SC: Antioxidant responses to oxidant-mediated lung diseases. Am J Physiol Lung Cell Mol Physiol 2002, 283:L246-L255.CrossRefPubMed
9.
Rahman I, Biswas SK, Kode A: Oxidant and antioxidant balance in the airways and airway diseases. Eur J Pharmacol 2006, 533:222–239.CrossRefPubMed
10.
Shapiro SD: The macrophage in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1999, 160:S29-S32.CrossRefPubMed
11.
12.
Hogg JC, Chu F, Utokaparch S, Woods R, Elliott WM, Buzatu L, Cherniack RM, Rogers RM, Sciurba FC, Coxson HO, et al.: The nature of small-airway obstruction in chronic obstructive pulmonary disease. N Engl J Med 2004, 350:2645–2653.CrossRefPubMed
13.
Tuder RM, Yoshida T, Arap W, Pasqualini R, Petrache I: State of the art. Cellular and molecular mechanisms of alveolar destruction in emphysema: an evolutionary perspective. Proc Am Thorac Soc 2006, 3:503–510.CrossRefPubMedPubMedCentral
14.
Cosio MG, Hale KA, Niewoehner DE: Morphologic and morphometric effects of prolonged cigarette smoking on the small airways. Am Rev Respir Dis 1980, 122:265–21.PubMed
15.
Hackett NR, Heguy A, Harvey BG, O'Connor TP, Luettich K, Flieder DB, Kaplan R, Crystal RG: Variability of antioxidant-related gene expression in the airway epithelium of cigarette smokers. Am J Respir Cell Mol Biol 2003, 29:331–343.CrossRefPubMed
16.
Spira A, Beane J, Shah V, Liu G, Schembri F, Yang X, Palma J, Brody JS: Effects of cigarette smoke on the human airway epithelial cell transcriptome. Proc Natl Acad Sci USA 2004, 101:10143–10148.CrossRefPubMedPubMedCentral
17.
Harvey BG, Heguy A, Leopold PL, Carolan BJ, Ferris B, Crystal RG: Modification of gene expression of the small airway epithelium in response to cigarette smoking. J Mol Med 2007, 85:39–53.CrossRefPubMed
18.
Pierrou S, Broberg P, O'Donnell RA, Pawlowski K, Virtala R, Lindqvist E, Richter A, Wilson SJ, Angco G, Moller S, et al.: Expression of genes involved in oxidative stress responses in airway epithelial cells of smokers with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2007, 175:577–586.CrossRefPubMed
19.
Heguy A, O'Connor TP, Luettich K, Worgall S, Cieciuch A, Harvey BG, Hackett NR, Crystal RG: Gene expression profiling of human alveolar macrophages of phenotypically normal smokers and nonsmokers reveals a previously unrecognized subset of genes modulated by cigarette smoking. J Mol Med 2006, 84:318–328.CrossRefPubMed
20.
Woodruff PG, Koth LL, Yang YH, Rodriguez MW, Favoreto S, Dolganov GM, Paquet AC, Erle DJ: A distinctive alveolar macrophage activation state induced by cigarette smoking. Am J Respir Crit Care Med 2005, 172:1383–1392.CrossRefPubMedPubMedCentral
21.
Russi TJ, Crystal RG: Bronchoalveolar lavage. In The Lung: Scientific Foundations. Edited by: Crystal RG, West JB, Weibel ER, Barnes PJ. Philadelphia: Lippencott-Raven, Inc; 1997:371–382.
22.
Bentley AR, Emrani P, Cassano PA: Genetic variation and gene expression in antioxidant related enzymes and risk of COPD: a systematic review. Thorax 2008, 63:956–961.CrossRefPubMedPubMedCentral
23.
Schraufstätter IU, Cochrane CG: Oxidants: types, sources, mechanisms of injury. In The Lung: Scientific Foundations. Second edition. Edited by: Crystal RG, West JB, Weibel ER, Barnes PJ. Philadelphia: Lippincott-Raven; 1997:2251–2258.
24.
25.
Expression profiling--best practices for data generation and interpretation in clinical trials Nat Rev Genet 2004, 5:229–237.
26.
Raman T, O'Connor TP, Hackett NR, Wang W, Harvey BG, Crystal RG: Establishment of quality control criteria to minimize experimental variability in microarray assessment of human airway epithelial gene expression. Am J Respir Crit Care Med 2008, 177:A208.CrossRef
27.
Kalsotra A, Strobel HW: Cytochrome P450 4F subfamily: at the crossroads of eicosanoid and drug metabolism. Pharmacol Ther 2006, 112:589–611.CrossRefPubMed
28.
29.
30.
Thomas ED, Ramberg RE, Sale GE, Sparkes RS, Golde DW: Direct evidence for a bone marrow origin of the alveolar macrophage in man. Science 1976, 192:1016–1018.CrossRefPubMed
31.
32.
Li N, Wang M, Oberley TD, Sempf JM, Nel AE: Comparison of the pro-oxidative and proinflammatory effects of organic diesel exhaust particle chemicals in bronchial epithelial cells and macrophages. J Immunol 2002, 169:4531–4541.CrossRefPubMed
33.
Dusinska M, Kovacikova Z, Vallova B, Collins A: Responses of alveolar macrophages and epithelial type II cells to oxidative DNA damage caused by paraquat. Carcinogenesis 1998, 19:809–812.CrossRefPubMed
34.
Pandolfi PP, Sonati F, Rivi R, Mason P, Grosveld F, Luzzatto L: Targeted disruption of the housekeeping gene encoding glucose 6-phosphate dehydrogenase (G6PD): G6PD is dispensable for pentose synthesis but essential for defense against oxidative stress. EMBO J 1995, 14:5209–5215.PubMedPubMedCentral
35.
Kozar RA, Weibel CJ, Cipolla J, Klein AJ, Haber MM, Abedin MZ, Trooskin SZ: Antioxidant enzymes are induced during recovery from acute lung injury. Crit Care Med 2000, 28:2486–2491.CrossRefPubMed
36.
Huang HC, Nguyen T, Pickett CB: Regulation of the antioxidant response element by protein kinase C-mediated phosphorylation of NF-E2-related factor 2. Proc Natl Acad Sci USA 2000, 97:12475–12480.CrossRefPubMedPubMedCentral
37.
Malhotra D, Thimmulappa R, Navas-Acien A, Sandford A, Elliott M, Singh A, Chen L, Zhuang X, Hogg J, Pare P, et al.: Decline in NRF2-regulated antioxidants in chronic obstructive pulmonary disease lungs due to loss of its positive regulator, DJ-1. Am J Respir Crit Care Med 2008, 178:592–604.CrossRefPubMedPubMedCentral
38.
Goven D, Boutten A, Lecon-Malas V, Marchal-Somme J, Amara N, Crestani B, Fournier M, Leseche G, Soler P, Boczkowski J, et al.: Altered Nrf2/Keap1-Bach1 equilibrium in pulmonary emphysema. Thorax 2008, 63:916–924.CrossRefPubMed
39.
Pitt BR, Schwarz M, Woo ES, Yee E, Wasserloos K, Tran S, Weng W, Mannix RJ, Watkins SA, Tyurina YY, et al.: Overexpression of metallothionein decreases sensitivity of pulmonary endothelial cells to oxidant injury. Am J Physiol 1997, 273:L856-L865.PubMed
40.
Gilks CB, Price K, Wright JL, Churg A: Antioxidant gene expression in rat lung after exposure to cigarette smoke. Am J Pathol 1998, 152:269–278.PubMedPubMedCentral
41.
Kondo T, Tagami S, Yoshioka A, Nishimura M, Kawakami Y: Current smoking of elderly men reduces antioxidants in alveolar macrophages. Am J Respir Crit Care Med 1994, 149:178–182.CrossRefPubMed
42.
McCusker K, Hoidal J: Selective increase of antioxidant enzyme activity in the alveolar macrophages from cigarette smokers and smoke-exposed hamsters. Am Rev Respir Dis 1990, 141:678–682.CrossRefPubMed
43.
Harju T, Kaarteenaho-Wiik R, Sirvio R, Paakko P, Crapo JD, Oury TD, Soini Y, Kinnula VL: Manganese superoxide dismutase is increased in the airways of smokers' lungs. Eur Respir J 2004, 24:765–771.CrossRefPubMed
44.
Couper KN, Blount DG, Riley EM: IL-10: the master regulator of immunity to infection. J Immunol 2008, 180:5771–5777.CrossRefPubMed
45.
Lee KS, Kim SR, Park SJ, Park HS, Min KH, Jin SM, Lee MK, Kim UH, Lee YC: Peroxisome proliferator activated receptor-gamma modulates reactive oxygen species generation and activation of nuclear factor-kappaB and hypoxia-inducible factor 1alpha in allergic airway disease of mice. J Allergy Clin Immunol 2006, 118:120–127.CrossRefPubMed
46.
Valledor AF, Ricote M: Nuclear receptor signaling in macrophages. Biochem Pharmacol 2004, 67:201–212.CrossRefPubMed
Metadata
Title
Disparate oxidant gene expression of airway epithelium compared to alveolar macrophages in smokers
Publication date
01-12-2009
Published in
Respiratory Research / Issue 1/2009
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/1465-9921-10-111

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WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

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