Skip to main content
Thorax logoLink to Thorax
. 2002 Feb;57(2):157–164. doi: 10.1136/thorax.57.2.157

Cell specific expression of peroxiredoxins in human lung and pulmonary sarcoidosis

V Kinnula 1, S Lehtonen 1, R Kaarteenaho-Wiik 1, E Lakari 1, P Paakko 1, S Kang 1, S Rhee 1, Y Soini 1
PMCID: PMC1746258  PMID: 11828047

Abstract

Background: Six proteins of the peroxiredoxin (Prx) family have recently been characterised which have the capacity to decompose hydrogen peroxide in vivo and in vitro. These proteins may have an important role in the protection of human lung against endogenous and exogenous oxidant stress. However, the expression and distribution of these proteins in healthy human lung and diseased lung tissue is unknown.

Methods: The cell specific expression of Prxs in healthy lung tissue from four non-smokers and in parenchymal tissue from 10 subjects with pulmonary sarcoidosis was investigated by immunohistochemistry, and expression of these proteins in various cultured lung cells and cells of bronchoalveolar lavage (BAL) fluid of controls and patients with sarcoidosis was assessed by Western blot analysis.

Results: All six Prxs could be synthesised in cultured human lung cells. The bronchial epithelium showed moderate to high expression of Prxs I, III, V and VI, the alveolar epithelium expressed mainly Prxs V and VI, and alveolar macrophages expressed mainly Prxs I and III. Granulomas of subjects with sarcoidosis expressed mainly Prxs I and III. Samples of BAL fluid from controls and from subjects with sarcoidosis had very similar findings, except that Prxs II and III had a tendency for increased immunoreactivity in sarcoidosis tissue.

Conclusions: Prxs I, III, V, and VI, in particular, have prominent and cell specific expression in human lung tissue. High expression of Prxs I and III in granulomas and alveolar macrophages of sarcoidosis parenchyma may have a significant effect on the oxidant burden and the progression of lung injury in this disease.

Full Text

The Full Text of this article is available as a PDF (306.2 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Cantin A. M., North S. L., Hubbard R. C., Crystal R. G. Normal alveolar epithelial lining fluid contains high levels of glutathione. J Appl Physiol (1985) 1987 Jul;63(1):152–157. doi: 10.1152/jappl.1987.63.1.152. [DOI] [PubMed] [Google Scholar]
  2. Chae H. Z., Kim H. J., Kang S. W., Rhee S. G. Characterization of three isoforms of mammalian peroxiredoxin that reduce peroxides in the presence of thioredoxin. Diabetes Res Clin Pract. 1999 Sep;45(2-3):101–112. doi: 10.1016/s0168-8227(99)00037-6. [DOI] [PubMed] [Google Scholar]
  3. Comhair S. A., Thomassen M. J., Erzurum S. C. Differential induction of extracellular glutathione peroxidase and nitric oxide synthase 2 in airways of healthy individuals exposed to 100% O(2) or cigarette smoke. Am J Respir Cell Mol Biol. 2000 Sep;23(3):350–354. doi: 10.1165/ajrcmb.23.3.4076. [DOI] [PubMed] [Google Scholar]
  4. Crapo J. D., Peters-Golden M., Marsh-Salin J., Shelburne J. S. Pathologic changes in the lungs of oxygen-adapted rats: a morphometric analysis. Lab Invest. 1978 Dec;39(6):640–653. [PubMed] [Google Scholar]
  5. Erzurum S. C., Danel C., Gillissen A., Chu C. S., Trapnell B. C., Crystal R. G. In vivo antioxidant gene expression in human airway epithelium of normal individuals exposed to 100% O2. J Appl Physiol (1985) 1993 Sep;75(3):1256–1262. doi: 10.1152/jappl.1993.75.3.1256. [DOI] [PubMed] [Google Scholar]
  6. Fridovich I. Superoxide radical and superoxide dismutases. Annu Rev Biochem. 1995;64:97–112. doi: 10.1146/annurev.bi.64.070195.000525. [DOI] [PubMed] [Google Scholar]
  7. Hemmann S., Blaser K., Crameri R. Allergens of Aspergillus fumigatus and Candida boidinii share IgE-binding epitopes. Am J Respir Crit Care Med. 1997 Dec;156(6):1956–1962. doi: 10.1164/ajrccm.156.6.9702087. [DOI] [PubMed] [Google Scholar]
  8. Holmgren A. Redox regulation by thioredoxin and thioredoxin reductase. Biofactors. 2000;11(1-2):63–64. doi: 10.1002/biof.5520110117. [DOI] [PubMed] [Google Scholar]
  9. Jin D. Y., Chae H. Z., Rhee S. G., Jeang K. T. Regulatory role for a novel human thioredoxin peroxidase in NF-kappaB activation. J Biol Chem. 1997 Dec 5;272(49):30952–30961. doi: 10.1074/jbc.272.49.30952. [DOI] [PubMed] [Google Scholar]
  10. Kang S. W., Baines I. C., Rhee S. G. Characterization of a mammalian peroxiredoxin that contains one conserved cysteine. J Biol Chem. 1998 Mar 13;273(11):6303–6311. doi: 10.1074/jbc.273.11.6303. [DOI] [PubMed] [Google Scholar]
  11. Kang S. W., Chae H. Z., Seo M. S., Kim K., Baines I. C., Rhee S. G. Mammalian peroxiredoxin isoforms can reduce hydrogen peroxide generated in response to growth factors and tumor necrosis factor-alpha. J Biol Chem. 1998 Mar 13;273(11):6297–6302. doi: 10.1074/jbc.273.11.6297. [DOI] [PubMed] [Google Scholar]
  12. Kinnula V. L., Crapo J. D., Raivio K. O. Generation and disposal of reactive oxygen metabolites in the lung. Lab Invest. 1995 Jul;73(1):3–19. [PubMed] [Google Scholar]
  13. Kinnula V. L., Yankaskas J. R., Chang L., Virtanen I., Linnala A., Kang B. H., Crapo J. D. Primary and immortalized (BEAS 2B) human bronchial epithelial cells have significant antioxidative capacity in vitro. Am J Respir Cell Mol Biol. 1994 Nov;11(5):568–576. doi: 10.1165/ajrcmb.11.5.7946385. [DOI] [PubMed] [Google Scholar]
  14. Koura T., Gon Y., Hashimoto S., Azuma A., Kudoh S., Fukuda Y., Sugawara I., Yodoi J., Horie T. Expression of thioredoxin in granulomas of sarcoidosis: possible role in the development of T lymphocyte activation. Thorax. 2000 Sep;55(9):755–761. doi: 10.1136/thorax.55.9.755. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Lakari E., Päkkö P., Kinnula V. L. Manganese superoxide dismutase, but not CuZn superoxide dismutase, is highly expressed in the granulomas of pulmonary sarcoidosis and extrinsic allergic alveolitis. Am J Respir Crit Care Med. 1998 Aug;158(2):589–596. doi: 10.1164/ajrccm.158.2.9711059. [DOI] [PubMed] [Google Scholar]
  16. Lakari E., Päkkö P., Pietarinen-Runtti P., Kinnula V. L. Manganese superoxide dismutase and catalase are coordinately expressed in the alveolar region in chronic interstitial pneumonias and granulomatous diseases of the lung. Am J Respir Crit Care Med. 2000 Feb;161(2 Pt 1):615–621. doi: 10.1164/ajrccm.161.2.9904091. [DOI] [PubMed] [Google Scholar]
  17. McDonald R. J., Berger E. M., Repine J. E. Alveolar macrophage antioxidants prevent hydrogen peroxide-mediated lung damage. Am Rev Respir Dis. 1991 May;143(5 Pt 1):1088–1091. doi: 10.1164/ajrccm/143.5_Pt_1.1088. [DOI] [PubMed] [Google Scholar]
  18. Oberley T. D., Verwiebe E., Zhong W., Kang S. W., Rhee S. G. Localization of the thioredoxin system in normal rat kidney. Free Radic Biol Med. 2001 Feb 15;30(4):412–424. doi: 10.1016/s0891-5849(00)00486-x. [DOI] [PubMed] [Google Scholar]
  19. Okado-Matsumoto A., Matsumoto A., Fujii J., Taniguchi N. Peroxiredoxin IV is a secretable protein with heparin-binding properties under reduced conditions. J Biochem. 2000 Mar;127(3):493–501. doi: 10.1093/oxfordjournals.jbchem.a022632. [DOI] [PubMed] [Google Scholar]
  20. Oury T. D., Chang L. Y., Marklund S. L., Day B. J., Crapo J. D. Immunocytochemical localization of extracellular superoxide dismutase in human lung. Lab Invest. 1994 Jun;70(6):889–898. [PubMed] [Google Scholar]
  21. Pietarinen-Runtti P., Lakari E., Raivio K. O., Kinnula V. L. Expression of antioxidant enzymes in human inflammatory cells. Am J Physiol Cell Physiol. 2000 Jan;278(1):C118–C125. doi: 10.1152/ajpcell.2000.278.1.C118. [DOI] [PubMed] [Google Scholar]
  22. Pietarinen P., Raivio K., Devlin R. B., Crapo J. D., Chang L. Y., Kinnula V. L. Catalase and glutathione reductase protection of human alveolar macrophages during oxidant exposure in vitro. Am J Respir Cell Mol Biol. 1995 Oct;13(4):434–441. doi: 10.1165/ajrcmb.13.4.7546773. [DOI] [PubMed] [Google Scholar]
  23. Powis G., Mustacich D., Coon A. The role of the redox protein thioredoxin in cell growth and cancer. Free Radic Biol Med. 2000 Aug;29(3-4):312–322. doi: 10.1016/s0891-5849(00)00313-0. [DOI] [PubMed] [Google Scholar]
  24. Rahman I., MacNee W. Regulation of redox glutathione levels and gene transcription in lung inflammation: therapeutic approaches. Free Radic Biol Med. 2000 May 1;28(9):1405–1420. doi: 10.1016/s0891-5849(00)00215-x. [DOI] [PubMed] [Google Scholar]
  25. Rahman I., van Schadewijk A. A., Hiemstra P. S., Stolk J., van Krieken J. H., MacNee W., de Boer W. I. Localization of gamma-glutamylcysteine synthetase messenger rna expression in lungs of smokers and patients with chronic obstructive pulmonary disease. Free Radic Biol Med. 2000 Mar 15;28(6):920–925. doi: 10.1016/s0891-5849(00)00179-9. [DOI] [PubMed] [Google Scholar]
  26. Reddel R. R., Ke Y., Gerwin B. I., McMenamin M. G., Lechner J. F., Su R. T., Brash D. E., Park J. B., Rhim J. S., Harris C. C. Transformation of human bronchial epithelial cells by infection with SV40 or adenovirus-12 SV40 hybrid virus, or transfection via strontium phosphate coprecipitation with a plasmid containing SV40 early region genes. Cancer Res. 1988 Apr 1;48(7):1904–1909. [PubMed] [Google Scholar]
  27. Seo M. S., Kang S. W., Kim K., Baines I. C., Lee T. H., Rhee S. G. Identification of a new type of mammalian peroxiredoxin that forms an intramolecular disulfide as a reaction intermediate. J Biol Chem. 2000 Jul 7;275(27):20346–20354. doi: 10.1074/jbc.M001943200. [DOI] [PubMed] [Google Scholar]
  28. Silcocks P. B. Measuring repeatability and validity of histological diagnosis--a brief review with some practical examples. J Clin Pathol. 1983 Nov;36(11):1269–1275. doi: 10.1136/jcp.36.11.1269. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Wong G. H., Goeddel D. V. Induction of manganous superoxide dismutase by tumor necrosis factor: possible protective mechanism. Science. 1988 Nov 11;242(4880):941–944. doi: 10.1126/science.3263703. [DOI] [PubMed] [Google Scholar]
  30. Yanagawa T., Iwasa S., Ishii T., Tabuchi K., Yusa H., Onizawa K., Omura K., Harada H., Suzuki H., Yoshida H. Peroxiredoxin I expression in oral cancer: a potential new tumor marker. Cancer Lett. 2000 Aug 1;156(1):27–35. doi: 10.1016/s0304-3835(00)00434-1. [DOI] [PubMed] [Google Scholar]

Articles from Thorax are provided here courtesy of BMJ Publishing Group

RESOURCES