Home LiteratureArticle Details
PMID: 3415672 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Inhibition of leucocyte elastase by heparin and its derivatives.

The Biochemical journal ·Vol. 252 ·No. 2 ·1988-06-01 ·Pages 515-9

Redini F, Tixier JM, Petitou M, Choay J, Robert L, Hornebeck W

Abstract

Leucocyte proteinases, e.g. leucocyte elastase and cathepsin G, are inhibited by heparin. The activities of pig pancreatic and Pseudomonas aeruginosa elastases are unaffected by this polysaccharide. Heparin derivatives of known Mr and degree of sulphation were isolated. The inhibition of leucocyte elastase by these oligosaccharides can be classified as tight-binding hyperbolic non-competitive. Ki values ranged from 40 nM to 100 microM and were found to be inversely correlated with the chain length of the oligosaccharides. Desulphated compounds lacked inhibitory potential towards leucocyte elastase. Over-O-sulphated di- and tetra-saccharides are more potent inhibitors than their over-N-sulphated counterparts. It is proposed that the therapeutic use of heparin and its derivatives could be extended to disease states such as emphysema and rheumatoid arthritis, where the role of leucocyte elastase has been clearly established.

MeSH Terms
Animals Heparin/analogs & derivatives,pharmacology Kinetics Leukocyte Elastase Leukocytes/enzymology Oligopeptides/metabolism Oligosaccharides/pharmacology Pancreatic Elastase/antagonists & inhibitors Protease Inhibitors/pharmacology Rats Structure-Activity Relationship
Chemicals
Oligopeptides Oligosaccharides Protease Inhibitors succinyl-trialanine-4-nitroanilide Heparin Pancreatic Elastase Leukocyte Elastase
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Redini F
C.N.R.S. U.A. 1174, Université Paris XII, C.H.U. Henri Mondor, Créteil, France.
Tixier J M
Petitou M
Choay J
Robert L
Hornebeck W
References (27)
27 references, click to expand
  1. Endothelial binding sites for heparin. Specificity and role in heparin neutralization.
    Biochem J. 1986 Sep 15;238(3):847-54 PMID: 2432885
  2. X-ray crystal structure of the complex of human leukocyte elastase (PMN elastase) and the third domain of the turkey ovomucoid inhibitor.
    EMBO J. 1986 Oct;5(10):2453-8 PMID: 3640709
  3. Graphical and statistical analysis of hyperbolic tight-binding inhibition.
    Biochem J. 1987 Jun 15;244(3):793-6 PMID: 3446192
  4. The determination of enzyme inhibitor constants.
    Biochem J. 1953 Aug;55(1):170-1 PMID: 13093635
  5. A controlled study of the effect of intermittent heparin therapy on the course of human coronary atherosclerosis.
    Circulation. 1956 Apr;13(4):489-98 PMID: 13356403
  6. A simple graphical method for determining the inhibition constants of mixed, uncompetitive and non-competitive inhibitors.
    Biochem J. 1974 Jan;137(1):143-4 PMID: 4206907
  7. A conductimetric method for the determination of sulphate and carboxyl groups in heparin and other mucopolysaccharides.
    Carbohydr Res. 1975 Jan;39(1):168-76 PMID: 1111963
  8. Neutral proteinases of human spleen. Purification and criteria for homogeneity of elastase and cathepsin G.
    Biochem J. 1976 May 1;155(2):255-63 PMID: 7244
  9. Chemistry of the hemostatic mechanism and its relationship to the action of heparin.
    Fed Proc. 1977 Jan;36(1):10-8 PMID: 63388
  10. Oxygen radicals mediate endothelial cell damage by complement-stimulated granulocytes. An in vitro model of immune vascular damage.
    J Clin Invest. 1978 May;61(5):1161-7 PMID: 207729
  11. Heparin: an old drug with a new paradigm.
    Science. 1979 Nov 2;206(4418):528-33 PMID: 386509
  12. Inhibition of human elastase from polymorphonuclear leucocytes by a glycosaminoglycan polysulfate (Arteparon).
    Biochem Pharmacol. 1980 Jun 15;29(12):1723-7 PMID: 6447504
  13. Heparins--anionic polyelectrolyte drugs.
    Pharmacol Rev. 1979 Jun;31(2):99-166 PMID: 399524
  14. Trial of heparin versus atenolol in prevention of myocardial infarction in intermediate coronary syndrome.
    Lancet. 1981 Jun 6;1(8232):1225-8 PMID: 6112564
  15. Inhibition of human elastase from polymorphonuclear leucocytes by gold sodium thiomalate and pentosan polysulfate (SP-54).
    Biochem Pharmacol. 1981 Apr 1;30(7):703-8 PMID: 6166299
  16. Effect of different elastase inhibitors on leukocyte elastase pre-adsorbed to elastin.
    Hoppe Seylers Z Physiol Chem. 1982 Apr;363(4):455-8 PMID: 6918355
  17. Effect of chloromethyl ketone on the progression of elastase-induced emphysema in hamsters.
    Am Rev Respir Dis. 1982 Jul;126(1):174-5 PMID: 6920251
  18. Inspiratory and expiratory partitioning of airway resistance during sleep in patients with sleep apnea.
    Am Rev Respir Dis. 1983 May;127(5):554-8 PMID: 6846936
  19. Interaction between human leukocyte elastase and chondroitin sulfate.
    Chem Biol Interact. 1984 Sep 1;51(1):1-11 PMID: 6430574
  20. Heparin and the atherosclerotic process.
    Pharmacol Rev. 1984 Jun;36(2):91-110 PMID: 6379681
  21. Heparin inhibition of polymorphonuclear leukocyte activation in vitro. A possible pharmacological approach to granulocyte-mediated vascular damage.
    Thromb Res. 1984 Sep 1;35(5):527-37 PMID: 6091291
  22. Extension and structural variability of the antithrombin-binding sequence in heparin.
    J Biol Chem. 1984 Oct 25;259(20):12368-76 PMID: 6490618
  23. Elastase-type activity of human serum. Its variation in chronic obstructive lung diseases and atherosclerosis.
    Clin Physiol Biochem. 1983;1(6):285-92 PMID: 6568131
  24. Synthetic inhibitors of human leukocyte elastase Part 1--Sulphated polysaccharides.
    Biochem Int. 1985 Feb;10(2):221-32 PMID: 2581575
  25. Eglin-c, a polypeptide derived from the medicinal leech, prevents human neutrophil elastase-induced emphysema and bronchial secretory cell metaplasia in the hamster.
    Am Rev Respir Dis. 1985 Dec;132(6):1155-61 PMID: 3907441
  26. Contribution of monosaccharide residues in heparin binding to antithrombin III.
    Biochemistry. 1985 Nov 5;24(23):6723-9 PMID: 4084555
  27. Inhibition by elastase inhibitors of the formyl Met Leu Phe-induced chemotaxis of rat polymorphonuclear leukocytes.
    Cell Biochem Funct. 1987 Apr;5(2):113-22 PMID: 3495371
Article Info
Journal
The Biochemical journal
Abbr.
Biochem J
ISSN
0264-6021
DOI
10.1042/bj2520515
Published
1988-06-01
Pages
515-9
Language
English
Region
England
NLM ID
2984726R
PMCID
PMC1149174
Subset
IM
External Links
PubMed source DOI: 10.1042/bj2520515 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2