Skip to main content

Interaction of Granulocyte Proteases with Inhibitors in Pulmonary Diseases

  • Chapter
Proteases

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 167))

Abstract

Sputum granulocytes were implicated as the source of proteolytic activity found in purulent bronchial secretions already by Opie.1 2 Final proof that a bulk of these proteases is of granulocytic origin was presented more recently, based on immunochemical studies utilizing specific antisera against the granulocyte proteases.3 The total concentration of these different granulocyte proteases is extremely high in purulent bronchial secretions, approaching a level of 0.5–1 g/l.3 4 In such secretions the proteases are present in a free, active form as well as in complex with the inhibitors.3 It seems reasonable to propose that these proteases are involved in the extensive tissue destructions seen in bronchiectasis, which is a rather common complication of chronic purulent bronchitis. Furthermore, pulmonary emphysema is currently thought to be due to a protease-antiprotease imbalance in the lung with uncontrolled digestion of the lung tissue, caused by granulocyte proteases — particularly elastase.5 This hypothesis is supported by the fact that persons with inherited deficiency of α1-antitrypsin, the main inhibitor of granulocyte elastase,6 show an increased susceptibility to emphysema.7 Furthermore, recent results indicate that the emphysema in cigarette smokers might be due in part to local suppression of α1-antitrypsin and also antileukoprotease in lung by oxidative agents present in cigarette smoke.8 9 In addition, granulocyte homogenates10 or purified granulocyte elastase11 cause emphysema when administered intratracheally to experimental animals. Macrophage elastase seems to be a less likely candidate to cause emphysema — at least as judged from the indirect evidence that this enzyme is poorly inhibited by α1-antitrypsin.12

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. E. L. Opie, Enzymes and anti-enzymes of inflammatory exudates, J Exp Med 7: 316 1905.

    Article  PubMed  CAS  Google Scholar 

  2. E. L. Opie, Intracellular digestion. The enzymes and anti-enzymes concerned, Physiol Rev 2: 552 1922.

    Google Scholar 

  3. K. Ohlsson and H. Tegner, Granulocyte collagenase, elastase and plasma protease inhibitors in purulent sputum, Europ J Clin Invest 5: 221 1975.

    PubMed  CAS  Google Scholar 

  4. D. Y. Twumasi and I. E. Liener, Proteases from purulent sputum. Purification and properties of the elastase and chymotrypsin-like enzymes, J Biol Chem 252: 1917 1977.

    PubMed  CAS  Google Scholar 

  5. C.-B. Laurell, Is emphysema in α1-antitrypsin deficiency a result of autodigestion? Editorial, Scand J Clin Lab Invest 28: 1 1971.

    Article  PubMed  CAS  Google Scholar 

  6. K. Ohlsson and I. Olsson, Neutral proteases of human granulocytes. III. Interaction between human granulocyte elastase and plasma protease inhibitors, Scand J Clin Lab Invest 34: 349 1974.

    Article  PubMed  CAS  Google Scholar 

  7. C.-B. Laurell and S. Eriksson, The electrophoretic α1-globulin pattern of serum in α1-antitrypsin deficiency. Scand J Clin Lab Invest 15: 132 1963.

    CAS  Google Scholar 

  8. A. Janoff and H. Karp, Possible mechanisms of emphysema in smokers. Cigarette smoke condensate suppresses protease inhibition in vittio, Amer Rev Resp Dis 116: 65 1977.

    PubMed  CAS  Google Scholar 

  9. K. Ohlsson, U. Fryksmark, and H. Tegner, The effect of cigarette smoke condensate on α1-antitrypsin, antileukoprotease and granulocyte elastase, Europ J Clin Invest 10: 373 1980.

    Article  PubMed  CAS  Google Scholar 

  10. B. Mass, T. Ikeda, D. R. Meranze, G. Weinbaum, and P. Kimbel, Induction of experimental emphysema: cellular and species specificity, Amer Rev Resp Dis 106: 384 1972.

    PubMed  CAS  Google Scholar 

  11. R. M. Senior, H. Tegner, C. Kuhn, K. Ohlsson, C. Barry, and J. A. Pierce, The induction of pulmonary emphysema with human leukocyte elastase, Amer Rev Resp Dis 116: 469 1977.

    PubMed  CAS  Google Scholar 

  12. L. M. Hinman, C. A. Stevens, R. A. Matthay, and J. B. L. Gee, Elastase and lysosome activities in human alveolar macrophages, Amer Rev Resp Dis 121: 263 1980.

    PubMed  CAS  Google Scholar 

  13. K. Ohlsson, Granulocyte proteases: their release and inhibition in the body, in: “Regulatory Proteolytic enzymes and their Inhibitors,” S. Magnusson et al., eds., Pergamon Press, Oxford and New York (1978).

    Google Scholar 

  14. K. Ohlsson and A.-S. Olsson, Immunoreactive granulocyte elastase in human serum, HoppeSeyler Z Physiol Chem 359: 1531 1978.

    Article  CAS  Google Scholar 

  15. K. Ohlsson, Polymorphonuclear leucocyte collagenase, In: “Collagenase in Normal and Pathological Connective Tissues,” P. E. Woolley and J. M. Evanson, eds., John Wiley & Sons Ltd. (1980).

    Google Scholar 

  16. H. Schiessler, M. Arnhold, and H. Fritz, Characterization of two proteinase inhibitors from human seminal plasma and spermatozoa, in: “Bayer-Symposium V Proteinase Inhibitors,” H. Fritz, H. Tschesche, L. J. Greene, and E. Truscheit, eds., Springer-Verlag, Berlin (1974).

    Google Scholar 

  17. O. Wallner and H. Fritz, Characterization of an acid stable proteinase inhibitor in human cervical mucus, Hoppe-Seyler Z Physiol Chem 355: 709 1974.

    Article  PubMed  CAS  Google Scholar 

  18. K. Ohlsson, H. Tegner, and U. Åkesson, Isolation and partial characterization of a low molecular weight acid stable protease inhibitor from human bronchial secretion, Hoppe-Seyler Z Physiol Chem 358: 583 1977.

    Article  PubMed  CAS  Google Scholar 

  19. H. Schiessler, K. Hochstrasser, and K. Ohlsson, Acid-stable inhibitors of granulocyte neutral proteases in human mucus secretions: Biochemistry and possible biological function, in: “Neutral Proteases of Human Polymorphonuclear Leukocytes,” K. Havemann and A. Janoff, eds., Urban and Schwarzenberg, Inc., Baltimore-Munich (1978).

    Google Scholar 

  20. U. Fryksmark, K. Ohlsson, Å. Polling, and H. Tegner, Distribution of antileukoprotease in upper respiratory mucosa, Ann Otol Rhinol Laryngol 91: 268 1982.

    PubMed  CAS  Google Scholar 

  21. B. Casslén, M. Rosengren, and K. Ohlsson, Localization and quantitation of a low molecular weight proteinase inhibitor, antileukoprotease, in the human uterus. Hoppe-Seyler Z Physiol Chem 362: 953 (1981).

    Article  PubMed  Google Scholar 

  22. B. Carlsson, On granulocyte proteases and protease inhibitors in otitis media, Thesis, Stockholm (1982).

    Google Scholar 

  23. J. A. Kramps. C. Franken, C. J. L. Meyer, and J. H. Dijkman, Localization of a low molecular weight protease inhibitor in serous secretory cells of the respiratory tract, J Histochem Cytochem 29: 712 1981.

    Article  PubMed  Google Scholar 

  24. B.-M. Jönsson, C. Löffler, and K. Ohlsson, Human granulocyte elastase is inhibited by the urinary trypsin inhibitor, Hoppe-Seyler Z Physiol Chem 363: 1167 1982.

    Article  PubMed  Google Scholar 

  25. B. J. Bromke and F. Kueppers, The major urinary protease inhibitor; simplified purification and characterization, Biochem Med 27: 56 1982.

    Article  PubMed  CAS  Google Scholar 

  26. K. Hochstrasser, H. Feuth, and K. Hochgesand, Proteinase inhibitors of the respiratory tract: Studies on the structural relationship between acid-stable inhibitors present in the respiratory tract, plasma and urine, in: “Bayer-Symposium V Proteinase Inhibitors,” H. Fritz, H. Tschesche, L. J. Greene, and E. Truscheit, eds., Springer-Verlag, Berlin, Heidelberg, New York (1974).

    Google Scholar 

  27. K. Hochstrasser and E. Wächter, Kunitz-type proteinase inhibitors derived by limited proteolysis of the inter-α-trypsin inhibitor, I, Hoppe-Seyler Z Physiol Chem 360: 1285 1979.

    Article  PubMed  CAS  Google Scholar 

  28. U. Fryksmark, K. Ohlsson, M. Rosengren, and H. Tegner, A radioimmunoassay for measurement and characterization of human antileukopro-tease in serum, Hopp-Seyler Z Physiol Chem 362: 1273 1981.

    Article  CAS  Google Scholar 

  29. A. Eddeland and K. Ohlsson, Studies on the pancreatic secretory trypsin inhibitor in plasma and its complex with trypsin in vivo and in vitro, Scand J Clin Lab Invest 38: 507 (1978).

    Article  PubMed  CAS  Google Scholar 

  30. F. Gauthier, U. Fryksmark, K. Ohlsson, and J. Bieth, Kinetics of the inhibition of leukocyte elastase by the bronchial inhibitor, Biochem Biophys Acta 700: 178 1982.

    Article  PubMed  CAS  Google Scholar 

  31. P. O. Ganrot, Inhibition of the trypsin α2, macroglobulin complex by the protease inhibitor from bovine lung, Arkiv för Kemi 26: 583 1967.

    CAS  Google Scholar 

  32. J. G. Bieth, M. Tourbez-Perrin, and F. Fochon, Inhibition of α2-macroglobulin-bound trypsin by soybean trypsin inhibitor, J Biol Chem 256: 7954 1981.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1984 Plenum Press, New York

About this chapter

Cite this chapter

Ohlsson, K., Fryksmark, U., Ohlsson, M., Tegner, H. (1984). Interaction of Granulocyte Proteases with Inhibitors in Pulmonary Diseases. In: Hörl, W.H., Heidland, A. (eds) Proteases. Advances in Experimental Medicine and Biology, vol 167. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-9355-3_25

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-9355-3_25

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4615-9357-7

  • Online ISBN: 978-1-4615-9355-3

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics