Skip to main content
Log in

An aminopeptidase of human neutrophil leucocytes — its possible role in enhanced vascular permeability

  • Histamine and Kinins
  • Published:
Agents and Actions Aims and scope Submit manuscript

Abstract

An aminopeptidase of human leukocyte lysosomes was partially purified by chromatography on SP-Sephadex, Sephadex G-200 and QAE-Sephadex. By QAE-Sephadex and isoelecric focusing it showed microheterogeneity, focusing at pH 3.7 and 4.1. By gel filtration its molecular weight was estimated to be approx. 200,000. The enzyme had leucine amino peptidase activity and pharmacological assays indicated that it converted lysyl- or methionyl-lysylbradykinin to bradykinin. Conversion of lysyl-bradykinin to bradykinin could be confirmed also by chromatography on CM-cellulose. When the neutrophil-derived enzyme acted on methionyl-lysyl-bradykinin it increased its effect of enhancing vascular permeability, when injected intradermally into guinea pigs. Thus the enzyme may play a role in neutrophil leukocyte-mediated vascular phenomena of the inflammatory reaction.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. E.G. Erdös, T. Nakajima, G. Ohima, A. Gecse andJ. Kato,Kininase and their Interactions with Other Systems, in:Chemistry and Biology of the Kallikrein-Kinin System in Health and Disease.Fogarty International Center Proc. No. 27 (Eds. J.J. Pisano and K.F. Austen; U.S. Gov. Printing Office, Washington, 1976).

    Google Scholar 

  2. H.Z. Movat, S.G. Steinberg, F.M. Habal andN.S. Ranadive,Demonstration of a Kinin-Generating Enzyme in the Lysosome of Human Polymorphonuclear Leukocytes, Lab. Invest.6, 669 (1973).

    Google Scholar 

  3. R. Reisfeld, U. Lewis andD. Williams,Disc Electrophoresis of Basis Proteins and Peptides on Polyacrylamide Gels, Nature195, 281 (1962).

    Google Scholar 

  4. B.J. Davis,Disc Electrophoresis II — Method and Application to Human Serum Proteins, Ann. N.Y. Acad. Sci.121, 404 (1964).

    Google Scholar 

  5. J.A. Goldbarg andA.M. Rutenberg,The Colorimetric Determination of Leucine Aminopeptidase in Urine and Serum of Normal Subjects and Patients with Cancer and other Diseases, Cancer11, 283 (1958).

    Google Scholar 

  6. F.M. Habal, H.Z. Movat andC.E. Burrowes,Isolation of Two Functionally Different Kininogens from Human Plasma — Separation from Proteinase Inhibitors and Interaction with Plasma Kallikrein, Biochem. Pharmacol.23, 2291 (1974).

    Google Scholar 

  7. K. Udaka, Y. Takeuchi andH.Z. Movat,Simple Method for Quantitation of Enhanced Vascular Permeability, Proc. Soc. Exp. Biol. Med.133, 1384 (1970).

    Google Scholar 

  8. T. Freeman,Trace Labelling with Radioiodine, in:Handbook of Experimental Immunology (Ed. D.M. Weir; Blackwell Sci. Publ., Oxford, 1967).

    Google Scholar 

  9. E. Habermann andB. Blennemann,Über Substrate und Reaktionsprodukte der kininbildenden Enzyme Trypsin, Serum- und Pankreaskallikrein sowie von Crotalusgift, Naunyn-Schmiedeberg's Arch. exp. Path. Pharm.249, 357 (1964).

    Google Scholar 

  10. M.E. Webster andJ.V. Pierce,The Nature of the Kallidins Released from Human Plasma by Kallikreins and Other Enzymes, Ann. N.Y. Acad. Sci.104, 91 (1963).

    Google Scholar 

  11. E.G. Erdös, A.G. Renfrew, E.M. Sloane andJ.R. Wohler,Enzymatic Studies on Bradykinin and Similar Peptides, Ann. N.Y. Acad. Sci.104, 222 (1963).

    Google Scholar 

  12. J.A. Guimarães, D.R. Borges, E.S. Prado andJ.L. Prado,Kinin-Converting Aminopeptidase from Human Serum, Biochem. Pharmacol.22, 3157 (1973).

    Google Scholar 

  13. V.K. Hopsu, K.K. Mäkinen andG.G. Glenner,Purification of a Mammalian Peptidase Selective for N-Terminal Arginine and Lysine Residues: Aminopeptidase B, Arch. Biochem. Biophys.114, 557 (1966).

    Google Scholar 

  14. D.R. Borges, J.L. Prado andJ.A. Guimarães,Characterization of a Kinin-Converting Arylaminopeptidase from Human Liver, Naunyn-Schmiedeberg's Arch. Pharm.281, 403 (1974).

    Google Scholar 

  15. C.M.W. Brandi, E.S. Prado, M.J.B.A. Prado andJ.L. Prado,Kinin-Converting Aminopeptidase from Human Urine, Partial Purification and Properties, Int. J. Biochem.7, 335 (1976).

    Google Scholar 

  16. J.D. Folds, I.R.H. Welsh andJ.K. Spitznagel,Neutral Proteases Confined to One Class of Lysosomes of Human Polymorphonuclear Leukocytes, Proc. Soc. Exp. Biol. Med.139, 461 (1972).

    Google Scholar 

  17. M.L. Reis, L. Okino andM. Rocha E. Silva,Comparative Pharmacological Actions of Bradykinin and Related Kinins of Larger Molecular Weight, Biochem. Pharmacol.20, 2935 (1971).

    Google Scholar 

  18. H.Z. Movat, J.O. Minta, M.J. Saya, F.M. Habal, C.E. Burrowes, S. Wasi andE. Pass,Neutrophil Generation of Permeability Enhancing Peptides from Plasma Substrates, in:Molecular and Biological Aspects of the Acute Allergic Reaction (Eds. S.G.O. Johansson, K. Strandberg and B. Üvnäs; Plenum Press, New York and London, 1976).

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

Supported by the Ontario Heart Foundation and the Medical Research Council of Canada (MT-1251).

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pas, E., Movat, H.Z. & Wasi, S. An aminopeptidase of human neutrophil leucocytes — its possible role in enhanced vascular permeability. Agents and Actions 8, 91–97 (1978). https://doi.org/10.1007/BF01972408

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01972408

Keywords

Navigation