Skip to main content

Advertisement

SpringerLink
Log in

Comparative aspects of murine proteinase 3

  • Short Communication
  • Published:
Rheumatology International Aims and scope Submit manuscript

Abstract

The neutrophilic granule protein proteinase 3 (PR3) is the preferred target antigen of anti-neutrophil cytoplasmic antibodies (ANCA) found in the serum of patients with Wegener’s granulomatosis, a systemic small-vessel vasculitis. Due to the lack of data concerning the murine homologue of human PR3, we assessed the neutrophil marker polypeptide PR3 in mice by generating a murine-specific PR3 antibody. In contrast to humans, peripheral blood leukocytes are not the main resource of murine PR3. Interestingly, we could show that the mouse bone marrow is the main PR3 source, indicating that it is a large reservoir for functional neutrophils. This pool of neutrophils could be rapidly mobilized after injection of IL-8. The development of the new PR3 antibody provides a new tool for studying the maturation processes of the murine hematopoietic system and will also support the generation of infectious disease or vasculitis mouse models.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

References

  1. Borregaard N, Cowland JB (1997) Granules of the human neutrophilic polymorphonuclear leukocyte. Blood 89(10):3503–3521

    PubMed  CAS  Google Scholar 

  2. Russell ES, Neufeld EF, Higgins CT (1951) Comparison of normal blood picture of young adults from 18 inbred strains of mice. Proc Soc Exp Biol Med 78(3):761–766

    PubMed  CAS  Google Scholar 

  3. Chervenick PA, Boggs DR, Marsh JC, Cartwright GE, Wintrobe MM (1968) Quantitative studies of blood and bone marrow neutrophils in normal mice. Am J Physiol 215(2):353–360

    PubMed  CAS  Google Scholar 

  4. Kallenberg CG, Brouwer E, Weening JJ, Tervaert JW (1994) Anti-neutrophil cytoplasmic antibodies: current diagnostic and pathophysiological potential. Kidney Int 46(1):1–15

    Article  PubMed  CAS  Google Scholar 

  5. Falk RJ, Jennette JC (1988) Anti-neutrophil cytoplasmic autoantibodies with specificity for myeloperoxidase in patients with systemic vasculitis and idiopathic necrotizing and crescentic glomerulonephritis. N Engl J Med 318(25):1651–1657

    Article  PubMed  CAS  Google Scholar 

  6. Jennette JC, Hoidal JR, Falk RJ (1990) Specificity of anti-neutrophil cytoplasmic autoantibodies for proteinase 3. Blood 75(11):2263–2264

    PubMed  CAS  Google Scholar 

  7. Brouwer E, Huitema MG, Klok PA et al (1993) Antimyeloperoxidase-associated proliferative glomerulonephritis: an animal model. J Exp Med 177(4):905–914

    Article  PubMed  CAS  Google Scholar 

  8. Foucher P, Heeringa P, Petersen AH et al (1999) Antimyeloperoxidase-associated lung disease An experimental model. Am J Respir Crit Care Med 160(3):987–994

    PubMed  CAS  Google Scholar 

  9. Heeringa P, Brouwer E, Klok PA et al (1996) Autoantibodies to myeloperoxidase aggravate mild anti-glomerular-basement-membrane-mediated glomerular injury in the rat. Am J Pathol 149(5):1695–1706

    PubMed  CAS  Google Scholar 

  10. Kobayashi K, Shibata T, Sugisaki T (1995) Aggravation of rat nephrotoxic serum nephritis by antimyeloperoxidase antibodies. Kidney Int 47(2):454–463

    Article  PubMed  CAS  Google Scholar 

  11. Little MA, Smyth CL, Yadav R et al (2005) Antineutrophil cytoplasm antibodies directed against myeloperoxidase augment leukocyte-microvascular interactions in vivo. Blood 106(6):2050–2058

    Article  PubMed  CAS  Google Scholar 

  12. Schreiber A, Xiao H, Falk RJ, Jennette JC (2006) Bone marrow-derived cells are sufficient and necessary targets to mediate glomerulonephritis and vasculitis induced by anti-myeloperoxidase antibodies. J Am Soc Nephrol 17(12):3355–3364

    Article  PubMed  Google Scholar 

  13. Xiao H, Heeringa P, Hu P et al (2002) Antineutrophil cytoplasmic autoantibodies specific for myeloperoxidase cause glomerulonephritis and vasculitis in mice. J Clin Invest 110(7):955–963

    PubMed  CAS  Google Scholar 

  14. Pfister H, Ollert M, Frohlich LF et al (2004) Antineutrophil cytoplasmic autoantibodies against the murine homolog of proteinase 3 (Wegener autoantigen) are pathogenic in vivo. Blood 104(5):1411–1418

    Article  PubMed  CAS  Google Scholar 

  15. Giuliano F, Warner TD (2002) Origins of prostaglandin E2: involvements of cyclooxygenase (COX)-1 and COX-2 in human and rat systems. J Pharmacol Exp Ther 303(3):1001–1006

    Article  PubMed  CAS  Google Scholar 

  16. Keir ME, Liang SC, Guleria I et al (2006) Tissue expression of PD-L1 mediates peripheral T cell tolerance. J Exp Med 203(4):883–895

    Article  PubMed  CAS  Google Scholar 

  17. Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254

    Article  PubMed  CAS  Google Scholar 

  18. Laterveer L, Lindley IJD, Hamilton MS, Willemze R, Fibbe WE (1995) Interleukin-8 induces rapid mobilization of hematopoietic stem-cells with radioprotective capacity and long-term myelolymphoid repopulating ability. Blood 85(8):2269–2275

    PubMed  CAS  Google Scholar 

  19. Clark-Lewis I, Schumacher C, Baggiolini M, Moser B (1991) Structure-activity relationships of interleukin-8 determined using chemically synthesized analogs. Critical role of NH2-terminal residues and evidence for uncoupling of neutrophil chemotaxis, exocytosis, and receptor binding activities. J Biol Chem 266(34):23128–23134

    PubMed  CAS  Google Scholar 

  20. Petrescu AJ, Milac AL, Petrescu SM, Dwek RA, Wormald MR (2004) Statistical analysis of the protein environment of N-glycosylation sites: implications for occupancy, structure, and folding. Glycobiology 14(2):103–114

    Article  PubMed  CAS  Google Scholar 

  21. Abul H, Abul A, Khan I, Mathew TC, Ayed A, Al Athary E (2001) Levels of IL-8 and myeloperoxidase in the lungs of pneumonia patients. Mol Cell Biochem 217(1–2):107–112

    Article  PubMed  CAS  Google Scholar 

  22. Aveskogh M, Lutzelschwab C, Huang MR, Hellman L (1997) Characterization of cDNA clones encoding mouse proteinase 3 (myeloblastine) and cathepsin G. Immunogenetics 46(3):181–191

    Article  PubMed  CAS  Google Scholar 

  23. Sturrock A, Franklin KF, Wu S, Hoidal JR (1998) Characterization and localization of the genes for mouse proteinase-3 (Prtn3) and neutrophil elastase (Ela2). Cytogenet Cell Genet 83(1–2):104–108

    Article  PubMed  CAS  Google Scholar 

  24. Belaaouaj A, Moog-Lutz C, Just J, Houzel-Charavel A, Shapiro SD, Cayre Y (1999) Genomic organization and chromosomal localization of mouse proteinase 3 (Myeloblastin). Mamm Genome 10(3):210–212

    Article  PubMed  CAS  Google Scholar 

  25. van der Geld YM, Hellmark T, Selga D et al (2007) Rats and mice immunised with chimeric human/mouse proteinase 3 produce autoantibodies to mouse Pr3 and rat granulocytes. Ann Rheum Dis 66(12):1679–1682

    Article  PubMed  Google Scholar 

  26. van der Veen BS, Heeringa P (2009) ANCA-small vessel vasculitides: what have we (not yet) learned from animal models? APMIS Suppl 127:21–26

    Article  PubMed  Google Scholar 

  27. Jenne DE, Frohlich L, Hummel AM, Specks U (1997) Cloning and functional expression of the murine homologue of proteinase 3: implications for the design of murine models of vasculitis. FEBS Lett 408(2):187–190

    Article  PubMed  CAS  Google Scholar 

  28. Goldschmeding R, van der Schoot CE, ten Bokkel Huinink D et al (1989) Wegener’s granulomatosis autoantibodies identify a novel diisopropylfluorophosphate-binding protein in the lysosomes of normal human neutrophils. J Clin Invest 84(5):1577–1587

    Article  PubMed  CAS  Google Scholar 

  29. Kao RC, Wehner NG, Skubitz KM, Gray BH, Hoidal JR (1988) Proteinase 3. A distinct human polymorphonuclear leukocyte proteinase that produces emphysema in hamsters. J Clin Invest 82(6):1963–1973

    Article  PubMed  CAS  Google Scholar 

  30. Niles JL, McCluskey RT, Ahmad MF, Arnaout MA (1989) Wegener’s granulomatosis autoantigen is a novel neutrophil serine proteinase. Blood 74(6):1888–1893

    PubMed  CAS  Google Scholar 

  31. Rao NV, Rao GV, Marshall BC, Hoidal JR (1996) Biosynthesis and processing of proteinase 3 in U937 cells. Processing pathways are distinct from those of cathepsin G. J Biol Chem 271(6):2972–2978

    Article  PubMed  CAS  Google Scholar 

  32. Garwicz D, Lindmark A, Hellmark T, Gladh M, Jogi J, Gullberg U (1997) Characterization of the processing and granular targeting of human proteinase 3 after transfection to the rat RBL or the murine 32D leukemic cell lines. J Leukoc Biol 61(1):113–123

    PubMed  CAS  Google Scholar 

  33. Jagels MA, Hugli TE (1992) Neutrophil chemotactic factors promote leukocytosis. A common mechanism for cellular recruitment from bone marrow. J Immunol 148(4):1119–1128

    PubMed  CAS  Google Scholar 

  34. Boxio R, Bossenmeyer-Pourie C, Steinckwich N, Dournon C, Nusse O (2004) Mouse bone marrow contains large numbers of functionally competent neutrophils. J Leukoc Biol 75(4):604–611

    Article  PubMed  CAS  Google Scholar 

  35. Baggiolini M, Clark-Lewis I (1992) Interleukin-8, a chemotactic and inflammatory cytokine. FEBS Lett 307(1):97–101

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors thank Ms. Huong Becker for technical assistance and Hannes Cash for his critical reading of the manuscript.

Author information

Authors and Affiliations

  1. First Department of Medicine, University Hospital Johannes-Gutenberg University Mainz, Langenbeckstrasse 1, 55131, Mainz, RLP, Germany

    Manfred Relle, Thomas Thomaidis, Peter R. Galle & Andreas Schwarting

  2. Sana Centre of Rheumatology Bad Kreuznach, Kaiser-Wilhelm-Straße 9-11, 55543, Bad Kreuznach, RLP, Germany

    Andreas Schwarting

Authors
  1. Manfred Relle
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Thomas Thomaidis
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Peter R. Galle
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Andreas Schwarting
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Manfred Relle.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Relle, M., Thomaidis, T., Galle, P.R. et al. Comparative aspects of murine proteinase 3. Rheumatol Int 31, 1105–1111 (2011). https://doi.org/10.1007/s00296-010-1672-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00296-010-1672-2

Keywords

Search

Navigation