Skip to main content
Log in

Analysis of Carbonylated Proteins in Bronchoalveolar Lavage of Patients with Diffuse Lung Diseases

  • Original Paper
  • Published:
Lung Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

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

  1. Rahman I, Biswas SK, Kode A (2006) Oxidant and antioxidant balance in the airways and airway diseases. Eur J Pharmacol 533:222–239

    Article  PubMed  CAS  Google Scholar 

  2. Misso NL, Thompson PJ (2005) Oxidative stress and antioxidant deficiencies in asthma: potential modification by diet. Redox Rep 10:247–255

    Article  PubMed  CAS  Google Scholar 

  3. Buss IH, Winterbourn CC (2002) Protein carbonyl measurement by ELISA. Methods Mol Biol 186:123–128

    PubMed  CAS  Google Scholar 

  4. 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

    PubMed  CAS  Google Scholar 

  5. 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

    Article  PubMed  CAS  Google Scholar 

  6. Lenz AG, Costabel U, Maier KL (1996) Oxidized BAL fluid proteins in patients with interstitial lung diseases. Eur Respir J 9:307–312

    Article  PubMed  CAS  Google Scholar 

  7. 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

    Article  PubMed  CAS  Google Scholar 

  8. 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

    PubMed  CAS  Google Scholar 

  9. 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

    Article  PubMed  CAS  Google Scholar 

  10. De Forge LE, Preston AM, Takeuchi E, et al. (1993) Regulation of IL8 gene expression by oxidative stress. J Biol Chem 268:25568–25576

    Google Scholar 

  11. 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

    Article  PubMed  CAS  Google Scholar 

  12. 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

    PubMed  CAS  Google Scholar 

  13. 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

    Article  PubMed  CAS  Google Scholar 

  14. 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

    Google Scholar 

  15. MacNee W, Rahman I (1995) Oxidants/antioxidants in idiopathic pulmonary fibrosis. Thorax 50:S53–S58

    Article  PubMed  Google Scholar 

  16. Wollheim FA, Denton CP, Abraham DJ (2001) 6th International workshop on scleroderma research. Arthritis Res 3:34–40

    Article  PubMed  CAS  Google Scholar 

  17. 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

    Article  PubMed  CAS  Google Scholar 

  18. ATS/ERS/WASOG (1999) Statement on Sarcoidosis. Eur Respir J 14:735–737

    Article  Google Scholar 

  19. ATS/ERS (2002) International multidisciplinary consensus classification of the idiophatic interstitial pneumonias. Am. J Respir Crit Care Med 165:277–304

    Google Scholar 

  20. 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

    Article  PubMed  CAS  Google Scholar 

  21. Carrington CB, Addington WW, Goff AM, et al. (1969) Chronic eosinophilic pneumonia. N Engl J Med 280:787–798

    Article  PubMed  CAS  Google Scholar 

  22. 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

    Article  PubMed  CAS  Google Scholar 

  23. 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

    Article  PubMed  CAS  Google Scholar 

  24. Starosta V, Griese M (2006) Protein oxidation by chronic pulmonary diseases in children. Pediatr Pulmonol 41:67–73

    Article  PubMed  CAS  Google Scholar 

  25. 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

    PubMed  CAS  Google Scholar 

  26. Demedts M, Behr J, Buhl R, et al. (2005) High-dose acetylcysteine in idiopathic pulmonary fibrosis. N Engl J Med 353:2229–2242

    Article  PubMed  CAS  Google Scholar 

  27. 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

    Article  PubMed  CAS  Google Scholar 

  28. 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

    Article  PubMed  CAS  Google Scholar 

  29. Mohr LC (2004) Hypersensitivity pneumonitis. Curr Opin Pulm Med 10:401–411

    Article  PubMed  Google Scholar 

  30. Fink JN, Ortega HG, Reynolds HY (2005) Needs and opportunities for research in hypersensitivity pneumonitis. Am J Respir Crit Care Med 171: 792–798

    Article  PubMed  Google Scholar 

  31. 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

    PubMed  CAS  Google Scholar 

  32. 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

    Article  PubMed  CAS  Google Scholar 

  33. 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

    Article  PubMed  CAS  Google Scholar 

  34. 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

    Article  PubMed  CAS  Google Scholar 

  35. Starke-Reed PE, Oliver CN (1989) Protein oxidation and proteolysis during aging and oxidative stress. Arch Biochem Biophys 275:559–567

    Article  PubMed  CAS  Google Scholar 

Download references

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.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Elena Bargagli.

Rights and permissions

Reprints and permissions

About this article

Cite this article

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

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00408-007-9001-6

Keywords

Navigation