Kinins IV pp 105-111 | Cite as

Interaction of Human Low Molecular Weight Kininogen with Human Mast Cell Tryptase

  • Lawrence B. Schwartz
  • Manfred Maier
  • Jocelyn Spragg
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 198A)


The capacity of purified tryptase, the major neutral tryptic protease of human lung mast cells, to serve as a kininogenase was examined with purified human low molecular weight kininogen (LMWK) as the substrate. Incubating of 25 mug of tryptase with LMWK for 2 to 30 minutes, with or without heparin, yielded no net time-dependent kinin release as determined on the estrous rat uterus. The 0.4 mug of kinin seen represented less than 10% of that released from excess LMWK by 5 mug of human urinary kallikrein in 5 min. Incubation at pH 5.5 with or without heparin did not significantly alter this result. LMWK did not appear by SDS-PAGE to be cleaved by tryptase either in the presence or absence of heparin. In contrast to its action on HMWK, tryptase did not extensively cleave LMWK, or destroy its reactivity with kallikrein.


Mast Cell Kinin Activity Human Neutrophil Elastase15 High Molecular Weight Kininogen Human Lung Mast Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Spragg, J., Talamo, R.C. and Austen, K.F.: Immunochemistry of bradykinin and immunologic activation of the kinin system. In: Bradykinin, Kallidin and Kallikrein ed, by E.G. Erdos. Springer pp. 531–549 (1970).CrossRefGoogle Scholar
  2. 2.
    Cochrane, C.G., Wuepper, K.D., Aiken, B.S., Revak, S.D. and Spiegelberg, H.L.: The interaction of Hageman factor and immune complexes. J. Clin. Invest. 51: 2736 (1972).PubMedCrossRefGoogle Scholar
  3. 3.
    Newball, H.H., Meier, H.L., Kaplan, A.P., Revak, S.D., Cochrane, C.G. and Lichtenstein, L.M.: Activation of Hageman factor by proteases released during antigen challenge of human lung. Trans. Assoc. Am. Phys. 94: 126 (1981).PubMedGoogle Scholar
  4. 4.
    Smith, P.L., Kagey-Sobotka, A., Bleecker, E.R., Traystman, R., Kaplan, A.P., Gralnick, H., Valentine, M.D., Permutt, S. and Lichtenstein, L.M.: Physiologic manifestations of human anaphylaxis. J. Clin. Invest. 66: 1072–1080 (1980).PubMedCrossRefGoogle Scholar
  5. 5.
    Ratnoff, O.D. and Nossel, H.L.: Wasp sting anaphylaxis. Blood 61: 132–139 (1983).PubMedGoogle Scholar
  6. 6.
    Newball, H.H., Talamo, R.C. and Lichtenstein, L.M.: Release of leukocyte kallikrein mediated by IgE. Nature 254: 635–636 (1975).PubMedCrossRefGoogle Scholar
  7. 7.
    Newball, H.H., Berninger, R.W., Talamo, R.C. and Lichtenstein, L.M.: Anaphylactic release of a basophil kallikrein-like activity. I. Purification and characterization. J. Clin. Invest. 64: 457–465 (1979).PubMedCrossRefGoogle Scholar
  8. 8.
    Newball, H.H., Meier, H.L., Kaplan, A.P., Revak, S.D., Cochrane, C.G. and Lichtenstein, L.M.: Anaphylactic release of human lung kinin- generating activities (LK-A’S). Fed. Proc. 39: 906A (1980).Google Scholar
  9. 9.
    Proud, D., Schulman, E.S., MacGlashan, D.W., Pierce, J.V. and Newball, H.H.: Anaphylactic release of a kininogenase from purified human lung mast cells. Clin. Res. 30: 165A (1982).Google Scholar
  10. 10.
    Proud, D. and Lichtenstein, L.M.: Human lung mast cell kininogenase: Apparent identity to tryptase. Fed. Proc. 43: 1807A (1984).Google Scholar
  11. 11.
    Schwartz, L.B., Lewis, R.A. and Austen, K.F,: Tryptase from human pulmonary mast cells. Purification and characterization. J. Biol. Chem. 256: 11939–11943 (1981).PubMedGoogle Scholar
  12. 12.
    Schwartz, L.B.: Monoclonal antibodies against human mast cell tryptase demonstrates shared antigenic sites on subunits of tryptase and selective localization of the enzyme to mast cells. J. Immunol. (In press).Google Scholar
  13. 13.
    Maier, M., Austen, K.F. and Spragg, J.: Characterization of the pro-coagulant chain derived from human high molecular weight kininogen (Fitzgerald factor) by human tissue kallikrein. Blood 62: 457–463 (1983).PubMedGoogle Scholar
  14. 14.
    Maier, M., Spragg, J, and Schwartz, L.B.: Inactivation of human high molecular weight kininogen by human mast cell tryptase. J. Immunol. 130: 2352–2356 (1983).PubMedGoogle Scholar
  15. 15.
    Kortmann, H., Bonner, G., Muller-Esterl, W., Jochum, M. and Fritz, H.: Limited and unspecific proteolysis of kininogens in acute necrotizing pancreatitis (ANP). Abstracts of the Kinin ?84 Savannah International Congress, Oct. 21–25 (1984).Google Scholar
  16. 16.
    Colman, R.W.: Regulation of the plasma kaliikrein-kininogen system. Abstracts of the Kinin f84 Savannah International Congress, Oct. 21–25 (1984).Google Scholar
  17. 17.
    Maier, M., Austen, K.F. and Spragg, J.: Purification of single chain human low molecular weight kininogen and demonstration of its cleavage by human urinary kallikrein. Anal. Biochem. 134: 336–346 (1983).PubMedCrossRefGoogle Scholar
  18. 18.
    Walsh, K.A.: Trypsinogens and trypsins of various species. Methodsin Enzymology XIX: 41 – 63 (1970).Google Scholar
  19. 19.
    ole-MoiYoi, O., Spragg, J. and Austen, K.F.: Structural studies of human urinary kallikrein (urokallikrein). Proc. Natl. Acad. Sci. USA 76: 3121–3125 (1979).Google Scholar
  20. 20.
    ole-MoiYoi, O., Pinkus, G.S., Seldin, D.C., Spragg, J. and Austen, K.F.: Structure, functional characteristics and immunohistochemical localization of human glandular kallikreins from kidney and pancreas. In: Plasma and Cellular Modulatory Proteins ed. by D.H. Bing and R.A. Rosenbaum. Boston Center for Blood Research pp. 183–201 (1981).Google Scholar
  21. 21.
    Silver, M.R., ole-MoiYoi, O., Austen, K.F. and Spragg, J.: An active site radioimmunoassay for urokallikrein and demonstration of a latent form of the enzyme. J. Immunol. 124: 1551–1555 (1980).Google Scholar
  22. 22.
    Spragg, J. and Austen, K.F.: The preparation of human kininogen. III. Enzymatic digestion and modification. Biochem. Pharmacol. 23: 781–791 (1974).PubMedCrossRefGoogle Scholar
  23. 23.
    Schwartz, L.B., Kawahara, M.S., Hugli, T.E., Vik, D., Fearon, D.T. and Austen, K.F.: Generation of C3a anaphylatoxin from human C3 by human mast cell tryptase. J. Immunol. 130: 1891–1895 (1983).PubMedGoogle Scholar
  24. 24.
    Orange, R.P. and Austen, K.F. The biological assay of slow reacting substances SRS-A, bradykinin, prostaglandins. In: Methods in Immunology and Immunochemistry, Vol. V ed. by C.A. Williams and M.W. Chase. Academic Press pp. 145–149 (1976).Google Scholar
  25. 25.
    Schwartz, L.B. and Austen, K.F.: Structure and function of the chemical mediators of mast cells. Prog. Allergy 34: 271–321 (1984).PubMedGoogle Scholar
  26. 26.
    Proud, D-, Togias, A., Naclerio, R.M., Crush, S.A., Norman, P.S. and Lichtenstein, L.M.: Kinins are generated in vivo following nasal airway challenge of allergic individuals with allergen. J. Clin. Invest. 72: 1678–1685 (1983).PubMedCrossRefGoogle Scholar
  27. 27.
    Hojima, R.L.: In vitro activation of the contact (Hageman Factor) system of plasma by heparin and chondroitin sulfate E. Blood 63: 1453–1459 (1984).Google Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • Lawrence B. Schwartz
    • 1
    • 2
    • 3
    • 4
  • Manfred Maier
    • 1
    • 2
    • 3
    • 4
  • Jocelyn Spragg
    • 1
    • 2
    • 3
    • 4
  1. 1.Medical College of VirginiaRichmondUSA
  2. 2.Institute of Medical Physiology, Medical FacultyUniversity of ViennaViennaAustria
  3. 3.Department of MedicineHarvard Medical SchoolUSA
  4. 4.Department of Rheumatology and ImmunologyBrigham and Women’s HospitalBostonUSA

Personalised recommendations