Advertisement

Kinins pp 345-359 | Cite as

The Cleavage of a Methionyl-Lysyl-Bradykinin-Like Peptide from Kininogen by a Protease of Human Neutrophil Leukocyte Lysosomes

  • Henry Z. Movat
  • Flavio M. Habal
  • David R. L. Macmorine
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 70)

Abstract

Polymorphonuclear (PMN) leukocytes are essential for the tissue and vascular injury associated with formation and deposition of antigen-antibody complexes (1). There are several mechanisms by which phlogistic agents derived from PMN-leukocyte lysosomes may act. Some act directly, other indirectly by generating vasoactive substances from certain protein substrates. Rabbit leukocytes contain cationic proteins which can act directly on the microcirculation or by releasing vasoactive amines from mast cells (2). These same cells contain acid cathepsins which can generate “leukokinins” from “leukokininogen” at acid pH (3). The acid protease can degrade also basement membrane (4). Basement membrane, elastin and cartilage matrix can be degraded also by a protease of human PMN-leukocytes at neutral pH (5), and collagen by a collagenase (6). By acting on the 3rd and 5th component complement lysates of human PMN-leukocytes can cleave anaphylatoxin-like substances (7, 8). Our own studies indicate that lysates of PMN-leukocyte lysosomes contain a protease capable of cleaving a kinin-like peptide from highly purified kininogen (9). The enzymes were obtained either by fractionating cell lysates or by interacting the cells with antigen-antibody complexes. In the latter case the hydrolases were released into the ambient fluid, and in the cell pellet the phagocytosing and degranulating cells were identified ultrastructurally as neutrophil leukocytes. Subsequently, the enzyme was obtained in partially purified form (10) and in a brief communication we reported on the properties of the highly purified protease with kininogenase activity (11), concluding that it is probably the same protease which degrades elastin, basement membrane and cartilage proteoglycan (5).

Keywords

Chloromethyl Ketone Leukocyte Elastase Neutrophil Leukocyte Kinin System Synthetic Kinin 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Movat, H.Z.: Allergic inflammation: The sequelae of antigenantibody formation. Symposium on Pathways to Inflammation. Fed. Proc. 35, in press.Google Scholar
  2. 2.
    Ranadive, N.S. and Cochrane, C.G.: Isolation and characterization of permeability factors from rabbit neutrophils. J. Exp. Med. 128: 605, 1968.PubMedCrossRefGoogle Scholar
  3. 3.
    Greenbaum, L.M., Pakash, A., Semente, G. and Johnson, M.: The leukokinin system: its role in fluid accumulation in malignancy and inflamnation. Agents and Actions 3: 332, 1973.PubMedCrossRefGoogle Scholar
  4. 4.
    Cochrane, C.G. and Aikin, B.S.: Polymorphonuclear leukocytes in immunologic reactions: The destruction of basement membrane in vivo and in vitro. J. Exp. Med. 124: 733, 1966.PubMedCrossRefGoogle Scholar
  5. 5.
    Janoff, A.: Human granulocyte elastase. Am. J. Path. 68 579, 1972.PubMedGoogle Scholar
  6. 6.
    Lazarus, G.S., Daniels, J.R. and Lian, J.: Granulocyte collagenase. Mechanism of collagen degradation. Am. J. Path. 613: 565, 1972.Google Scholar
  7. 7.
    Taubman, S.G., Goldschmidt, P.R. and Lepow, I.H.: Effect of lysosomal enzymes from human leukocytes on human complement components. Fed. Proc. 29: 434, 1970.Google Scholar
  8. 8.
    Goldstein, I.M. and Weissmann, G.: Generation of C5-derived lysosomal enzyme releasing activity (C5a) by lysates of leukocyte lysosomes. J. Immunol. 113: 1583, 1974.PubMedGoogle Scholar
  9. 9.
    Movat, H.Z., Steinberg, S.G., Habal, F.M. and Ranadive, N.S.: Demonstration of a kinin-generating enzyme in the lysosomes of human polymorphonuclear leukocytes. Lab. Invest. 29: 669, 1973.PubMedGoogle Scholar
  10. 10.
    Movat, H.Z.: Release of a kinin-forming enzyme from human polymorphonuclear leukocytes following interaction with immune complexes. In: Allergology, Proceedings of the VIII International Congress of Allergology, Yamamura, Y., ed., Excerpta Medica, Amsterdam, 1974.Google Scholar
  11. 11.
    Movat, H.Z. and Habal, F.M.: Kininogenases of PMN-leukocyte lysosomes. In: Chemistry and Biology of the Kallikrein-Kinin System in Health and Disease. Pisano, J.J. and Austen, K.F., eds., Fogarty Internat. Center Proc. No. 27, U.S. Gov. Printing Office, Washington, 1975.Google Scholar
  12. 12.
    Habal, F.M., Movat, H.Z. and Burrowes, C.E.: Isolation of two functionally different kininogens from human plasma. Separation from proteinase inhibitors and interaction with plasma kallikrein. Biochem. Pharmacol. 23: 2291, 1974.PubMedCrossRefGoogle Scholar
  13. 13.
    Habal, F.M. and Movat, H.Z.: Some physicocehmical and functional differences between low and high molecular weight kininogens of human plasma. In: Chemistry and Biology of the Kallikrein-Kinin System in Health and Disease. Pisano, J.J. and Austen, K.F., eds., Fogarty Internat. Center Proc. No. 27, U.S. Gov. Printing Office, Washington, 1975.Google Scholar
  14. 14.
    Movat, H.Z., Soltay, M.J., Fuller, P.J. and Ozge-Anwar, A.H.: The relationship between the plasma kinin system and the contact phase of blood coagulation in man. In: Vasopeptides, Chemistry, Pharmacology and Pathophysiology, Back, N. and Sicuteri, F., eds., Plenum Press, New York, 1972.Google Scholar
  15. 15.
    Reisfeld, R., Lewis, U. and Williams, D.: Disc gel electrophoresis of basic proteins and peptides on polyacrylamide gels. Nature 195: 281, 1962.PubMedCrossRefGoogle Scholar
  16. 16.
    Weber, K. and Osborn, M.: The reliability of molecular weight determination by dodecyl sulfate-polyacrylamide gel electrophoresis. J. Biol. Chem. 244: 4406, 1969.PubMedGoogle Scholar
  17. 17.
    Fish, W.W., Mann, K. and Tanford, C.: The estimation of polypeptide chain molecular weights by gel filtration in 6 M guanidine hydrochloride. J. Biol. Chem. 244: 4989, 1969.PubMedGoogle Scholar
  18. 18.
    Martin, R.G. and Ames, B.N.: A method for determining the sedimentation behaviour of enzymes: Application to protein mixtures. J. Biol. Chem. 236.: 1372, 1961.PubMedGoogle Scholar
  19. 19.
    Movat, H.Z., Poon, M.-C. and Takeuchi, Y.: The kinin system of human plasma. I. Isolation of a low molecular weight activator of prekallikrein. Int. Arch. Allergy 40: 89, 1971.PubMedCrossRefGoogle Scholar
  20. 20.
    Abiko, Y., Iwamoto, M., and Shimizu, M.: Plasminogen-plasmin system. I. Purification and properties of human plasminogen. J. Biochem. 64: 743, 1968.PubMedGoogle Scholar
  21. 21.
    Wasi, S., Murray, R.K., Macmorine, D.R.L. and Movat, H.Z.: The role of PMN-leukocyte lysosomes in tissue injury and inflammation. II. Studies on the proteolytic activity of PMN-leukocyte lysosomes of the rabbit. Brit. J. Exp. Path. 47: 411, 1966.PubMedGoogle Scholar
  22. 22.
    Janoff, A.: Alanine p-nitrophenol elastase activity of human leucocyte granules. Biochem. J. 114: 157, 1969.PubMedGoogle Scholar
  23. 23.
    Fishman, W.H.: β-glucuronidase. In: Methods of Enzymatic Analysis, H.U. Bergmeyer, ed., Academic Press, New York, 1963.Google Scholar
  24. 24.
    Bergmeyer, H.U., Brent, E. and Hess, B.: Lactic dehydrogenase. In: Methods of Enzymatic Analysis, H.U. Bergmeyer, ed., Academic Press, New York, 1963.Google Scholar
  25. 25.
    Movat, H.Z., Habal, F.M. and Macmorine, D.R.L.: The generation of a vasoactive peptide from kininogen by a protease of human neutrophil leukocyte lysosomes. Agents and Actions, in press.Google Scholar
  26. 26.
    Hedrick, J.L. and Smith, A.J.: Size and charge isomer separation and estimation of molecular weights of proteins by disc gel electrophoresis. Arch. Biochem. Biophys. 126: 155, 1968.PubMedCrossRefGoogle Scholar
  27. 27.
    Freeman, T.: Trace labelling with radioiodine. In: Handbook of Experimental Immunology, D.M. Weir, ed., Blackwell, Oxford, 1967.Google Scholar
  28. 28.
    Tuhy, P.M. and Powers, J.C.: Inhibition of human elastase by peptide chloromethyl ketones. FEBS Letters 50: 359, 1975.PubMedGoogle Scholar
  29. 29.
    Habermann, E. and Blennemann, G.: Uber Substrate und Reaktionsprodukte der kininbildenden Enzyme Trypsin, Serum-und Pankreaskallikrein sowie von Crotalusgift. Naunyn-Schmied. Arch. Exp. Path. Pharm. 249: 357, 1964.CrossRefGoogle Scholar
  30. 30.
    Folds, J.D., Welsh, I.R.H. and Spitznagel, J.K.: Neutral proteases confined to one class of lysosomes of human polymorphonuclear leukocytes. Proc. Soc. Exp. Biol. Med. 139: 461, 1972.PubMedGoogle Scholar
  31. 31.
    Erdos, E.G., Nakajima, T., Oshima, G., Gecse, A. and Kato, J.: Kininases and their interactions with other systems, In: Chemistry and Biology of the Kallikrein-Kinin System in Health and Disease, Pisano, J.J. and Austen, K.F., eds., Fogarty Internat. Center Proc. No. 27, U.S. Gov. Printing Office, Washington, 1975.Google Scholar
  32. 32.
    Behal, F. and Folds, J.D.: Acrylamidase of neisseria cataralis. Arch. Biochem. Biophys. 121: 364, 1967.PubMedCrossRefGoogle Scholar
  33. 33.
    Reiss, M.L., Okino, L. and Rocha e Silva, M.: Comparative pharmacological actions of bradykinin and related kinins of larger molecular weights. Biochem. Pharmacol. 20: 2935, 1971.CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1976

Authors and Affiliations

  • Henry Z. Movat
    • 1
  • Flavio M. Habal
    • 1
  • David R. L. Macmorine
    • 1
  1. 1.Division of Experimental Pathology, Department of Pathology, and Institute of ImmunologyUniversity of TorontoTorontoCanada

Personalised recommendations