Abstract
Diffuse lung diseases (DLD) are a heterogeneous group of diseases with different etiopathogenesis, clinical course, and prognosis. It has been demonstrated that oxidative stress can contribute to the pathogenesis of these diseases. In the present study we measured carbonylated protein concentrations in the BAL of patients with sarcoidosis, pulmonary fibrosis associated with systemic sclerosis, idiopathic pulmonary fibrosis, and for the first time in patients with chronic eosinophilic pneumonia and extrinsic allergic alveolitis. Our aim was to further investigate oxidation products in diffuse lung diseases. Oxidatively modified protein concentrations were increased in the BAL of patients than in that of controls (0.22 nmol/mg protein vs 0.05 nmol/mg protein; p < 0.001) and in each group of disease versus controls, suggesting that proteins that have become dysfunctional by oxidation could play a role in the pathogenesis of diffuse lung diseases. Further studies in a greater number of patients are needed to understand the contribution of oxidatively modified proteins to the pathogenesis of DLD and, in particular, to the development of extrinsic allergic alveolitis where the highest levels of carbonylated proteins were found.
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Abbreviations
- BAL:
-
bronchoalveolar lavage
- DLD:
-
diffuse lung diseases
- S:
-
sarcoidosis
- SSc:
-
pulmonary fibrosis associated with systemic sclerosis
- IPF:
-
idiopathic pulmonary fibrosis
- EAA:
-
extrinsic allergic alveolitis
- CEP:
-
chronic eosinophilic pneumonia
References
Rahman I, Biswas SK, Kode A (2006) Oxidant and antioxidant balance in the airways and airway diseases. Eur J Pharmacol 533:222–239
Misso NL, Thompson PJ (2005) Oxidative stress and antioxidant deficiencies in asthma: potential modification by diet. Redox Rep 10:247–255
Buss IH, Winterbourn CC (2002) Protein carbonyl measurement by ELISA. Methods Mol Biol 186:123–128
Chevion M, Berenshtein E, Stadtman E (2000) Human studies related to protein oxidation: protein carbonyl content as a marker of damage. Free Radic Res 33(Suppl):S99–S108
Dalle-Donne I, Rossi R, Giustarini D, Milzani A, Colombo R (2003) Protein carbonyl groups as biomarkers of oxidative stress. Clin Chim Acta 329:23–38
Lenz AG, Costabel U, Maier KL (1996) Oxidized BAL fluid proteins in patients with interstitial lung diseases. Eur Respir J 9:307–312
Rottoli P, Magi B, Perari MG, et al. (2005) Cytokine profile and proteome analysis in BAL of patients with sarcoidosis, pulmonary fibrosis associated to systemic sclerosis and idiopathic pulmonary fibrosis. Proteomics 5:1423–1430
Selman M, King TE, Pardo A, ATS, ERS, ACCP (2001) Idiopathic pulmonary fibrosis: prevailing and evolving hypotheses about its pathogenesis and implications for therapy. Ann Intern Med 134:136–151
Behr J, Degenkolb B, Krombach F, Vogelmeier C (2002) Intracellular glutathione and BAL cells in fibrosing alveolitis: effects of N-acetylcysteine. Eur Respir J 19:906–911
De Forge LE, Preston AM, Takeuchi E, et al. (1993) Regulation of IL8 gene expression by oxidative stress. J Biol Chem 268:25568–25576
Lenz AG, Hinze-Heyn H, Schneider A, et al. (2004) Influence of inflammatory mechanisms on the redox balance in interstitial lung disease. Respir Med 98:737–745
Mata M, Ruiz A, Cerda M, et al. (2003) Oral N-acetylcysteine reduces bleomycin-induced lung damage and mucin Muc5ac expression in rats. Eur Respir J 22:900–905
Kuwano K, Nakashima N, Inoshima I, et al. (2003) Oxidative stress in lung epithelial cells from patients with idiopathic interstitial pneumonias. Eur Respir J 21:232–240
Cantin A, Hubbard RC, Crystal RG (1990) Glutathione deficiency in the epithelial lining fluid of the lower respiratory tract in idiopathic pulmonary fibrosis. Am Rev Respir Dis 141:124–128
MacNee W, Rahman I (1995) Oxidants/antioxidants in idiopathic pulmonary fibrosis. Thorax 50:S53–S58
Wollheim FA, Denton CP, Abraham DJ (2001) 6th International workshop on scleroderma research. Arthritis Res 3:34–40
Rottoli P, Magi B, Cianti R, et al. (2005) Carbonylated proteins in BAL of patients with sarcoidosis, pulmonary fibrosis associated with systemic sclerosis and idiopathic pulmonary fibrosis. Proteomics 5:2612–2618
ATS/ERS/WASOG (1999) Statement on Sarcoidosis. Eur Respir J 14:735–737
ATS/ERS (2002) International multidisciplinary consensus classification of the idiophatic interstitial pneumonias. Am. J Respir Crit Care Med 165:277–304
Richerson HB, Berstein IL, Fink JN, et al. (1989) Guidelines for the clinical evaluation of hypersensitivity pneumonitis: report of the subcommitee on hypersensitivity pneumonitis. J Allergy Clin Immunol 84:839–844
Carrington CB, Addington WW, Goff AM, et al. (1969) Chronic eosinophilic pneumonia. N Engl J Med 280:787–798
Bradford MM (1976) A rapid and sensitive method for the quantification of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254
Dalle-Donne I, Scaloni A, Giustarini D, et al. (2005) Proteins as biomarkers of oxidative/nitrosative stress in diseases: the contribution of redox proteomics. Mass Spectrom Rev 24:55–99
Starosta V, Griese M (2006) Protein oxidation by chronic pulmonary diseases in children. Pediatr Pulmonol 41:67–73
Strausz J, Muller-Quernheim J, Steppling H, Ferlinz R (1990) Oxygen radical production by alveolar inflammatory cells in idiopathic pulmonary fibrosis. Am Rev Respir Dis 141:124–128
Demedts M, Behr J, Buhl R, et al. (2005) High-dose acetylcysteine in idiopathic pulmonary fibrosis. N Engl J Med 353:2229–2242
Psathakis K, Papatheodorou G, Platani M, et al. (2004) 8-isoprostane, a marker of oxidative stress, is increased in expired breath condensate of patients with pulmonary sarcoidosis. Chest 125:1005–1011
Tiitto LH, Peltoniemi MJ, Kaarteenaho-Wiik RL, et al. (2004) Cell-specific regulation of gamma-glutamylcysteine synthetase in human interstitial lung disease. Hum Pathol 35:832–839
Mohr LC (2004) Hypersensitivity pneumonitis. Curr Opin Pulm Med 10:401–411
Fink JN, Ortega HG, Reynolds HY (2005) Needs and opportunities for research in hypersensitivity pneumonitis. Am J Respir Crit Care Med 171: 792–798
Behr J, Degenkolb B, Beinert T, Krombach F, Vogelmeier C (2000) Pulmonary glutathione levels in acute episodes of Farmer’s lung. Am J Respir Crit Care Med 161:1968–1971
Higashi A, Higashi N, Tsuburai T, et al. (2005) Involvement of eicosanoids and surfactant protein D in extrinsic allergic alveolitis. Eur Respir J 26:1069–1073
Bargagli E, Bigliazzi C, Leonini A, et al. (2005) Tryptase concentrations in bronchoalveolar lavage from patients with chronic eosinophilic pneumonia. Clin Sci 108:273–276
Schock BC, Young IS, Brown V, et al. (2003) Antioxidants and oxidative stress in BAL fluid of atopic asthmatic children. Pediatr Res 53:375–381
Starke-Reed PE, Oliver CN (1989) Protein oxidation and proteolysis during aging and oxidative stress. Arch Biochem Biophys 275:559–567
Acknowledgments
This study was supported by Ministry of University and Research (MIUR), Italy. The authors thank Dr. Collodoro for performing the bronchoscopies with bronchoalveolar lavages and Dr. Refini for lung function tests.
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Bargagli, E., Penza, F., Vagaggini, C. et al. Analysis of Carbonylated Proteins in Bronchoalveolar Lavage of Patients with Diffuse Lung Diseases. Lung 185, 139–144 (2007). https://doi.org/10.1007/s00408-007-9001-6
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DOI: https://doi.org/10.1007/s00408-007-9001-6