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. 1990 Nov;137(5):1077–1082.

Pathogenesis of antigen-induced arthritis in mice deficient in neutrophil elastase and cathepsin G.

R Pettipher 1, J Edwards 1, S Cruwys 1, E Jessup 1, J Beesley 1, B Henderson 1
PMCID: PMC1877666  PMID: 2240159

Abstract

The contribution of neutrophil-derived elastase and cathepsin G to joint pathology has been examined in immune arthritis in the mouse. Neutrophils from beige mice are genetically deficient in lysosomal elastase and cathepsin G, but have normal levels of the acid hydrolases, beta-glucuronidase, and N-acetyl-beta-glucosaminidase. The development of antigen-induced arthritis in normal mice has been compared with that in beige mice. The pattern of synovitis (both leukocyte accumulation and plasma leakage) were indistinguishable in normal and beige mice. Cartilage proteoglycan depletion was quantified by measuring the decrease in safranin O staining intensity, and this, too, was unaltered in mice lacking elastase and cathepsin G. These results suggest that neutrophil elastase and cathepsin G do not contribute to these aspects of joint pathology in antigen-induced arthritis in the mouse.

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Selected References

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

  1. Brackertz D., Mitchell G. F., Mackay I. R. Antigen-induced arthritis in mice. I. Induction of arthritis in various strains of mice. Arthritis Rheum. 1977 Apr;20(3):841–850. doi: 10.1002/art.1780200314. [DOI] [PubMed] [Google Scholar]
  2. Cawston T. E., Mercer E., de Silva M., Hazleman B. L. Metalloproteinases and collagenase inhibitors in rheumatoid synovial fluid. Arthritis Rheum. 1984 Mar;27(3):285–290. doi: 10.1002/art.1780270306. [DOI] [PubMed] [Google Scholar]
  3. Edwards J. C., Read N., Trefty B., Coulstock J., Henderson B. Quantitative histological analysis of antigen-induced arthritis in the rabbit. Br J Exp Pathol. 1988 Oct;69(5):739–748. [PMC free article] [PubMed] [Google Scholar]
  4. Hadler N. M., Spitznagel J. K., Quinet R. J. Lysosomal enzymes in inflammatory synovial effusions. J Immunol. 1979 Aug;123(2):572–577. [PubMed] [Google Scholar]
  5. Hunneyball I. M., Crossley M. J., Spowage M. Pharmacological studies of antigen-induced arthritis in BALB/c mice. I. Characterization of the arthritis and the effects of steroidal and non-steroidal anti-inflammatory agents. Agents Actions. 1986 Jun;18(3-4):384–393. doi: 10.1007/BF01965002. [DOI] [PubMed] [Google Scholar]
  6. Hunneyball I. M., Crossley M. J., Spowage M. Pharmacological studies of antigen-induced arthritis in BALB/c mice. II. The effects of second-line antirheumatic drugs and cytotoxic agents on the histopathological changes. Agents Actions. 1986 Jun;18(3-4):394–400. doi: 10.1007/BF01965003. [DOI] [PubMed] [Google Scholar]
  7. Johnson K. J., Varani J., Oliver J., Ward P. A. Immunologic vasculitis in beige mice with deficiency of leukocytic neutral protease. J Immunol. 1979 May;122(5):1807–1811. [PubMed] [Google Scholar]
  8. Kiviranta I., Tammi M., Jurvelin J., Sämänen A. M., Helminen H. J. Fixation, decalcification, and tissue processing effects on articular cartilage proteoglycans. Histochemistry. 1984;80(6):569–573. [PubMed] [Google Scholar]
  9. Kruijsen M. W., van den Berg W. B., van de Putte L. B., van den Broek W. J. Detection and quantification of experimental joint inflammation in mice by measurement of 99mTc-pertechnetate uptake. Agents Actions. 1981 Dec;11(6-7):640–642. doi: 10.1007/BF01978775. [DOI] [PubMed] [Google Scholar]
  10. Oronsky A. L., Perper R. J. Connective tissue-degrading enzymes of human leukocytes. Ann N Y Acad Sci. 1975 Jun 13;256:233–253. doi: 10.1111/j.1749-6632.1975.tb36050.x. [DOI] [PubMed] [Google Scholar]
  11. Pettipher E. R., Henderson B., Moncada S., Higgs G. A. Leucocyte infiltration and cartilage proteoglycan loss in immune arthritis in the rabbit. Br J Pharmacol. 1988 Sep;95(1):169–176. doi: 10.1111/j.1476-5381.1988.tb16561.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Pipoly D. J., Crouch E. C. Degradation of native type IV procollagen by human neutrophil elastase. Implications for leukocyte-mediated degradation of basement membranes. Biochemistry. 1987 Sep 8;26(18):5748–5754. doi: 10.1021/bi00392a025. [DOI] [PubMed] [Google Scholar]
  13. Schalkwijk J., Joosten L. A., van den Berg W. B., van de Putte L. B. Experimental arthritis in C57black/6 normal and beige (Chediak-Higashi) mice: in vivo and in vitro observations on cartilage degradation. Ann Rheum Dis. 1988 Nov;47(11):940–946. doi: 10.1136/ard.47.11.940. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Schalkwijk J., van den Berg W. B., van de Putte L. B., Joosten L. A., van den Bersselaar L. Cationization of catalase, peroxidase, and superoxide dismutase. Effect of improved intraarticular retention on experimental arthritis in mice. J Clin Invest. 1985 Jul;76(1):198–205. doi: 10.1172/JCI111946. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Schrijver G., Schalkwijk J., Robben J. C., Assmann K. J., Koene R. A. Antiglomerular basement membrane nephritis in beige mice. Deficiency of leukocytic neutral proteinases prevents the induction of albuminuria in the heterologous phase. J Exp Med. 1989 Apr 1;169(4):1435–1448. doi: 10.1084/jem.169.4.1435. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Takeuchi K. H., McGarry M. P., Swank R. T. Elastase and cathepsin G activities are present in immature bone marrow neutrophils and absent in late marrow and circulating neutrophils of beige (Chediak-Higashi) mice. J Exp Med. 1987 Nov 1;166(5):1362–1376. doi: 10.1084/jem.166.5.1362. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Tvedten H. W., Till G. O., Ward P. A. Mediators of lung injury in mice following systemic activation of complement. Am J Pathol. 1985 Apr;119(1):92–100. [PMC free article] [PubMed] [Google Scholar]
  18. Woolley D. E., Crossley M. J., Evanson J. M. Collagenase at sites of cartilage erosion in the rheumatoid joint. Arthritis Rheum. 1977 Jul-Aug;20(6):1231–1239. doi: 10.1002/art.1780200612. [DOI] [PubMed] [Google Scholar]

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