Inhibition by heparin of platelet activation induced by neutrophil-derived cathepsin G

Virgilio Evangelista, Paolo Piccardoni, Norma Maugeri, Giovanni De Gaetano, Chiara Cerletti

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Heparin is the most widely used anticoagulant drug for prevention and treatment of thrombosis. However, inhibition of blood coagulation might not fully explain the antithrombic activity of this drug. The present study shows that different heparin preparations (50 nM) completely human platelet aggregation, serotonin release and thromboxane B2 production induced by purified neutrophil-derived cathepsin G (E.C. No. 3.4.21.20). This inhibitory effect was not related to the anticoagulant property of the compounds, since a heparin preparation with an activated active site for antithrombin II was also effective. Heparins inhibited the protease activity of the enzyme over the same range of concentrations. Since the effect of cathepsin G on platelets requires an intact proteolytic active site, the inhibitory effect of the drugs on cathepsin G-induced platelet activation may be explained by a blockade activity. Heparins were also shownto reduce platelet activation induced by cathepsin G released from activated polymorphonuclear leucocytes in mixed cell suspensions. As polymorphonuclear leucocytes might contribute to both arterial and venous thrombosis through platelet activation induced by the release of cathepsin G, this novel property of heparin could be used its antithrombotic efficacy.

Original languageEnglish
Pages (from-to)401-405
Number of pages5
JournalEuropean Journal of Pharmacology
Volume216
Issue number3
DOIs
Publication statusPublished - Jun 17 1992

Fingerprint

Cathepsin G
Platelet Activation
Heparin
Neutrophils
Anticoagulants
Catalytic Domain
Thromboxane B2
Fibrinolytic Agents
Antithrombins
Blood Coagulation
Platelet Aggregation
Venous Thrombosis
Serotonin
Suspensions
Thrombosis
Peptide Hydrolases
Blood Platelets
Enzymes
Pharmaceutical Preparations

Keywords

  • Cathepsin G
  • Heparin
  • Neutrophils
  • Platelets

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

Inhibition by heparin of platelet activation induced by neutrophil-derived cathepsin G. / Evangelista, Virgilio; Piccardoni, Paolo; Maugeri, Norma; De Gaetano, Giovanni; Cerletti, Chiara.

In: European Journal of Pharmacology, Vol. 216, No. 3, 17.06.1992, p. 401-405.

Research output: Contribution to journalArticle

@article{6d9e355fdcea42e3b8d9f6382d89f4d3,
title = "Inhibition by heparin of platelet activation induced by neutrophil-derived cathepsin G",
abstract = "Heparin is the most widely used anticoagulant drug for prevention and treatment of thrombosis. However, inhibition of blood coagulation might not fully explain the antithrombic activity of this drug. The present study shows that different heparin preparations (50 nM) completely human platelet aggregation, serotonin release and thromboxane B2 production induced by purified neutrophil-derived cathepsin G (E.C. No. 3.4.21.20). This inhibitory effect was not related to the anticoagulant property of the compounds, since a heparin preparation with an activated active site for antithrombin II was also effective. Heparins inhibited the protease activity of the enzyme over the same range of concentrations. Since the effect of cathepsin G on platelets requires an intact proteolytic active site, the inhibitory effect of the drugs on cathepsin G-induced platelet activation may be explained by a blockade activity. Heparins were also shownto reduce platelet activation induced by cathepsin G released from activated polymorphonuclear leucocytes in mixed cell suspensions. As polymorphonuclear leucocytes might contribute to both arterial and venous thrombosis through platelet activation induced by the release of cathepsin G, this novel property of heparin could be used its antithrombotic efficacy.",
keywords = "Cathepsin G, Heparin, Neutrophils, Platelets",
author = "Virgilio Evangelista and Paolo Piccardoni and Norma Maugeri and {De Gaetano}, Giovanni and Chiara Cerletti",
year = "1992",
month = "6",
day = "17",
doi = "10.1016/0014-2999(92)90437-9",
language = "English",
volume = "216",
pages = "401--405",
journal = "European Journal of Pharmacology",
issn = "0014-2999",
publisher = "Elsevier",
number = "3",

}

TY - JOUR

T1 - Inhibition by heparin of platelet activation induced by neutrophil-derived cathepsin G

AU - Evangelista, Virgilio

AU - Piccardoni, Paolo

AU - Maugeri, Norma

AU - De Gaetano, Giovanni

AU - Cerletti, Chiara

PY - 1992/6/17

Y1 - 1992/6/17

N2 - Heparin is the most widely used anticoagulant drug for prevention and treatment of thrombosis. However, inhibition of blood coagulation might not fully explain the antithrombic activity of this drug. The present study shows that different heparin preparations (50 nM) completely human platelet aggregation, serotonin release and thromboxane B2 production induced by purified neutrophil-derived cathepsin G (E.C. No. 3.4.21.20). This inhibitory effect was not related to the anticoagulant property of the compounds, since a heparin preparation with an activated active site for antithrombin II was also effective. Heparins inhibited the protease activity of the enzyme over the same range of concentrations. Since the effect of cathepsin G on platelets requires an intact proteolytic active site, the inhibitory effect of the drugs on cathepsin G-induced platelet activation may be explained by a blockade activity. Heparins were also shownto reduce platelet activation induced by cathepsin G released from activated polymorphonuclear leucocytes in mixed cell suspensions. As polymorphonuclear leucocytes might contribute to both arterial and venous thrombosis through platelet activation induced by the release of cathepsin G, this novel property of heparin could be used its antithrombotic efficacy.

AB - Heparin is the most widely used anticoagulant drug for prevention and treatment of thrombosis. However, inhibition of blood coagulation might not fully explain the antithrombic activity of this drug. The present study shows that different heparin preparations (50 nM) completely human platelet aggregation, serotonin release and thromboxane B2 production induced by purified neutrophil-derived cathepsin G (E.C. No. 3.4.21.20). This inhibitory effect was not related to the anticoagulant property of the compounds, since a heparin preparation with an activated active site for antithrombin II was also effective. Heparins inhibited the protease activity of the enzyme over the same range of concentrations. Since the effect of cathepsin G on platelets requires an intact proteolytic active site, the inhibitory effect of the drugs on cathepsin G-induced platelet activation may be explained by a blockade activity. Heparins were also shownto reduce platelet activation induced by cathepsin G released from activated polymorphonuclear leucocytes in mixed cell suspensions. As polymorphonuclear leucocytes might contribute to both arterial and venous thrombosis through platelet activation induced by the release of cathepsin G, this novel property of heparin could be used its antithrombotic efficacy.

KW - Cathepsin G

KW - Heparin

KW - Neutrophils

KW - Platelets

UR - http://www.scopus.com/inward/record.url?scp=0026712862&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026712862&partnerID=8YFLogxK

U2 - 10.1016/0014-2999(92)90437-9

DO - 10.1016/0014-2999(92)90437-9

M3 - Article

C2 - 1425930

AN - SCOPUS:0026712862

VL - 216

SP - 401

EP - 405

JO - European Journal of Pharmacology

JF - European Journal of Pharmacology

SN - 0014-2999

IS - 3

ER -