Effects of glycosaminoglycans on platelet and leucocyte function: Role of N-sulfation

Grazyna Rajtar, Egidio Marchi, Giovanni de Gaetano, Chiara Cerletti

Research output: Contribution to journalArticlepeer-review

Abstract

The effect of glycosaminoglycans (GAGs) such as sulodexide, low molecular mass dermatan sulfate, heparin and some derivatives with different degrees and types of sulfation was studied on cathepsin G- or thrombin-stimulated platelets and n-formyl-methionyl-leucyl-phenylalanine (fMLP)-stimulated polymorphonuclear leucocytes (PMNs). All GAGs (0.01-20 μg/mL) inhibited both platelet aggregation induced by cathepsin G and its catalytic activity. Thrombin-induced platelet aggregation in contrast was only prevented by heparin, sulodexide and dermatan (2-100 μg/mL). All GAGs, except 2-O,N-desulfated heparin, inhibited β-glucuronidase and lysozyme release, as well as β-glucuronidase activity and PMN Superoxide production by the peptide fMLP. The efficacy of GAGs was clearly dependent on the degree and type of sulfation since dermatan and N-desulfated heparins were comparatively less effective. The observation that heparin and other GAGs inhibit platelet activation induced by the PMN protease cathepsin G may help determine whether mechanisms of action other than anticoagulation are critical in the antithrombotic activity of heparin and related compounds.

Original languageEnglish
Pages (from-to)958-960
Number of pages3
JournalBiochemical Pharmacology
Volume46
Issue number5
DOIs
Publication statusPublished - Sep 1 1993

ASJC Scopus subject areas

  • Pharmacology

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