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Altered serum levels of human neutrophil peptides (HNP) and human beta-defensin 2 (hBD2) in Wegener’s granulomatosis

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Abstract

Defensins are highly conserved peptides with antimicrobial and immunomodulatory functions. Due to their chemotactic properties on mononuclear cells, including dendritic cells and macrophages, defensins may contribute to granuloma formation in Wegener’s granulomatosis (WG). In order to explore whether these peptides might be involved in WG pathogenesis, sera of patients were screened to detect altered defensin levels. For this purpose, serum and EDTA-blood of patients with WG (n = 17; aged 54.8 ± 15.5 years) and age- and sex-matched healthy controls (n = 24; aged 55.5 ± 16.8 years) were collected. Levels of neutrophil α-defensins (human neutrophil peptides, HNP) and β-defensin (hBD) 2 and 3 in serum were measured by ELISA. By this means, WG patients displayed higher serum levels of hBD2 and HNP when compared to controls. Furthermore, serum hBD2 was raised in patients with meningeal granulomas (n = 4) or in those undergoing treatment with cyclophosphamide (n = 4). In order to detect whether increased gene expression in polymorphonuclear cells is responsible for the elevated defensin levels, real-time polymerase chain reaction with gene-specific primers was performed. Expression of specific mRNA in polymorphonuclear cells was observed for HNP only, but did not parallel HNP serum levels, suggesting that degranulation rather than increased gene expression may be responsible for increased HNP serum levels in WG. In conclusion, elevated serum levels of HNP and hBD2 in WG patients suggest a role for both defensins in WG pathogenesis.

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References

  1. Schneider JJ, Unholzer A, Schaller M, Schäfer-Korting M, Korting HC (2005) Human defensins. J Mol Med 83:587–595

    Article  PubMed  CAS  Google Scholar 

  2. Yang D, Chertov O, Bykoskaia SN, Chen Q, Buffo MJ, Shogan J, Anderson M, Schröder J-M, Wang JM, Howard OMZ, Oppenheim JJ (1999) Beta-defensins: linking innate and adaptive immunity through dendritic and T cell ccr6. Science 286:525–528

    Article  PubMed  CAS  Google Scholar 

  3. Yang D, Biragyn A, Hoover DM, Lubkowski J, Oppenheim JJ (2004) Multiple roles of antimicrobial defensins, cathelicidins, and eosionphil-derived neurotoxin in host defence. Annu Rev Immunol 22:181–215

    Article  PubMed  Google Scholar 

  4. Sthoeger ZM, Bezalel S, Chapnik N, Asher I, Froy O (2009) High alpha-defensin levels in patients with systemic lupus erythematosus. Immunology 127:116–122

    Article  PubMed  CAS  Google Scholar 

  5. Vordenbäumen S, Fischer-Betz R, Timm D, Sander O, Chehab G, Richter J, Bleck E, Schneider M (2010) Elevated levels of human beta-defensin 2 (hbd2) and human neutrophil peptides (hnp) in systemic lupus erythematosus. Lupus in press

  6. Rehaume LM, Hancock RE (2008) Neutrophil-derived defensins as modulators of innate immune function. Crit Rev Immunol 28:185–200

    PubMed  CAS  Google Scholar 

  7. Mallow EB, Harris A, Salzman A, Russel JP, DeBerardinis RJ, Ruchelli E, Bevins CL (1996) Human enteric defensins. J Biol Chem 271:4038–4045

    Article  PubMed  CAS  Google Scholar 

  8. Vordenbäumen S, Pilic D, Otte J-M, Schmitz F, Schmidt-Choudhury A (2009) Defensins are differentially expressed with respect to the anatomic region in the upper gastrointestinal tract of children. J Pediatr Gastroenterol Nutr 49:139–142

    Article  PubMed  Google Scholar 

  9. Becker MN, Diamond G, Verghese MW, Randell SH (2000) Cd14-dependent lipopolysaccharide-induced beta-defensin-2 expression in human tracheobronchial epithelium. J Biol Chem 275:29731–29736

    Article  PubMed  CAS  Google Scholar 

  10. Fahlgren A, Hammarstrom S, Danielsson A, Hammarstom ML (2004) Beta-defensin-3 and -4 in intestinal epithelial cells display increased mrna expression in ulcerative colitis. Clin Exp Immunol 137:379–385

    Article  PubMed  CAS  Google Scholar 

  11. Vordenbäumen S, Pilic D, Otte J-M, Schmitz F, Schmidt-Choudhury A (2010) Defensin-mrna-expression in the upper gastrointestinal tract is modulated in celiac disease and helicobacter-pylori -positive children. J Pediatr Gastroenterol Nutr 50:596–600

    Article  PubMed  Google Scholar 

  12. Zhang L, Yu W, He T, Yu J, Caffrey RE, Dalmasso EA, Fu S, Pham T, Mei J, Ho JJ, Zhang W, Lopez P, Ho DD (2002) Contribution of human alpha-defensins 1, 2, and 3 to the anti-hiv-activity of cd8 antiviral factor. Science 298:995–1000

    Article  PubMed  CAS  Google Scholar 

  13. Duits LA, Ravensbergen B, Rademaker M, Hiemstra PS, Nibbering PH (2002) Expression of beta-defensin 1 and 2 mrna by human monocytes, macrophages and dendritic cells. Immunology 106:517–525

    Article  PubMed  CAS  Google Scholar 

  14. Moosig F, Lamprecht P, Gross WL (2008) Wegener’s granulomatosis: the current view. Clin Rev Allergy Immunol 35:19–21

    Article  PubMed  CAS  Google Scholar 

  15. Hagen EC, Daha MR, Hermans J, Andrassy K, Csernok E, Gaskin G, Lesavere P, Lüdemann J, Rasmussen N, Sinicio RA, Wiik A, van der Woude FJ (1998) Diagnostic value of standardized assays for anti-neutrophil cytoplasmic antibodies in idiopathic systemic vasculitis. Kidney Int 53:743–753

    Article  PubMed  CAS  Google Scholar 

  16. Csernok E, Moosig F, Gross WL (2008) Pathways to anca production: from differentiation of dendritic cells by proteinase 3 to b lymphocyte maturation in wegener’s granuloma. Clin Rev Allergy Immunol 34:300–306

    Article  PubMed  CAS  Google Scholar 

  17. Tanaka S, Edberg JC, Chatham W, Fassina G, Kimberly RP (2003) Fc(gamma)riiib allele-sensitive release of alpha-defensins: anti-neutrophile cytoplasmic antibody-induced release of chemotaxins. J Immunol 171:6090–6096

    PubMed  CAS  Google Scholar 

  18. Röhrl J, Yang D, Oppenheim JJ, Hehlgans T (2010) Human b-defensin 2 and 3 and their mouse orthologs induce chemotaxis through interaction with ccr2. J Immunol 184:6688–6694

    Article  PubMed  Google Scholar 

  19. Leavitt RY, Fauci AS, Bloch DA, Michel BA, Hunder GC, Arend WP, Calabrese LH, Fries JF, Lie JT, Lightfoot RWJ (1990) The american college of rheumatology 1990 criteria for the classification of Wegner’s granulomatosis. Arthritis Rheum 33:1101–1107

    Article  PubMed  CAS  Google Scholar 

  20. Mukae H, Matsumoto N, Ashitani J, Mahimoto H, Kadota J, Nakazato M, Kohno S, Matsukura S (1996) Neutrophil-related cytokines and neutrophil products in bronchoalveolar lavage fluid. Eur Respir J 9:1950–1954

    Article  PubMed  CAS  Google Scholar 

  21. Tamiya H, Tani K, Miyata J, Sato K, Urata T, Lkhagvaa B, Otsuka S, Shigekiyo S, Sone S (2006) Defensin- and cathepsin g-anca in systemic lupus erythematosus. Rheumatol Int 27:147–152

    Article  PubMed  CAS  Google Scholar 

  22. Srivastava MD, Alexander F, Tuthill RJ (2005) Immunology of cutaneous vasculitis associated with both etanercept and infliximab. Scand J Immunol 61:329–336

    Article  PubMed  CAS  Google Scholar 

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Acknowledgment

Financial support information: this work was supported by an unconditional grant form the “Hiller-Stiftung”.

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Authors and Affiliations

  1. Section of Rheumatology, Department of Endocrinology, Diabetology and Rheumatology, Heinrich Heine University Düsseldorf, Moorenstr. 5, 40225, Düsseldorf, Germany

    Stefan Vordenbäumen, Daniel Timm, Ellen Bleck, Jutta Richter, Rebecca Fischer-Betz, Gamal Chehab, Oliver Sander & Matthias Schneider

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  1. Stefan Vordenbäumen
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  2. Daniel Timm
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  3. Ellen Bleck
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  4. Jutta Richter
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  5. Rebecca Fischer-Betz
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  6. Gamal Chehab
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  7. Oliver Sander
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  8. Matthias Schneider
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Correspondence to Stefan Vordenbäumen.

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Vordenbäumen, S., Timm, D., Bleck, E. et al. Altered serum levels of human neutrophil peptides (HNP) and human beta-defensin 2 (hBD2) in Wegener’s granulomatosis. Rheumatol Int 31, 1251–1254 (2011). https://doi.org/10.1007/s00296-010-1702-0

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  • DOI: https://doi.org/10.1007/s00296-010-1702-0

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