Size-fractionated heparins have differential effects on human neutrophil function in vitro

2.50
Hdl Handle:
http://hdl.handle.net/10541/70419
Title:
Size-fractionated heparins have differential effects on human neutrophil function in vitro
Authors:
Lever, R; Lo, W; Faraidoun, M; Amin, V; Brown, R; Gallagher, John T; Page, C
Abstract:
BACKGROUND AND PURPOSE: Heparin is known to possess a range of activities, other than effects on blood coagulation, many of which are anti-inflammatory. Effects with potential anti-inflammatory applications include the inhibition of elastase release from neutrophils, as well as the adhesion of these cells to vascular endothelium. In the present study we aimed to investigate whether fractionation of heparin may yield molecules with enhanced or specific effects on human neutrophil function. EXPERIMENTAL APPROACH: Fractions of defined molecular size were obtained from heparin by different methods and assessed for their effects on elastase release induced by formyl Met-Leu-Phe (fMLP), from neutrophils, in some cases following the priming of these cells with tumour necrosis factor-alpha (TNF-alpha). Effects of the fractions on neutrophil adhesion to interleukin-1beta (IL-beta)-stimulated human umbilical vein endothelial cells (HUVECs) were also examined. KEY RESULTS: Elastase release was inhibited by very low molecular weight fractions of heparin, with an apparent minimum chain length of 10 saccharides required for full effect. In contrast, neutrophil-endothelial adhesion was unaffected by these fractionated heparins, suggesting that certain non-anticoagulant actions of heparin may be lost by such an approach. CONCLUSIONS AND IMPLICATIONS: These data suggest that an optimum chain length of heparin possibly exists for certain non-anticoagulant actions of heparin, which may prove to be useful in the design of novel drugs with specific anti-inflammatory actions.
Affiliation:
Department of Pharmacology, School of Pharmacy, University of London, London, UK. rebecca.lever@pharmacy.ac.uk
Citation:
Size-fractionated heparins have differential effects on human neutrophil function in vitro. 2007, 151 (6):837-43 Br. J. Pharmacol.
Journal:
British Journal of Pharmacology
Issue Date:
Jul-2007
URI:
http://hdl.handle.net/10541/70419
DOI:
10.1038/sj.bjp.0707298
PubMed ID:
17533420
Type:
Article
Language:
en
ISSN:
0007-1188
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorLever, R-
dc.contributor.authorLo, W-
dc.contributor.authorFaraidoun, M-
dc.contributor.authorAmin, V-
dc.contributor.authorBrown, R-
dc.contributor.authorGallagher, John T-
dc.contributor.authorPage, C-
dc.date.accessioned2009-06-12T15:36:44Z-
dc.date.available2009-06-12T15:36:44Z-
dc.date.issued2007-07-
dc.identifier.citationSize-fractionated heparins have differential effects on human neutrophil function in vitro. 2007, 151 (6):837-43 Br. J. Pharmacol.en
dc.identifier.issn0007-1188-
dc.identifier.pmid17533420-
dc.identifier.doi10.1038/sj.bjp.0707298-
dc.identifier.urihttp://hdl.handle.net/10541/70419-
dc.description.abstractBACKGROUND AND PURPOSE: Heparin is known to possess a range of activities, other than effects on blood coagulation, many of which are anti-inflammatory. Effects with potential anti-inflammatory applications include the inhibition of elastase release from neutrophils, as well as the adhesion of these cells to vascular endothelium. In the present study we aimed to investigate whether fractionation of heparin may yield molecules with enhanced or specific effects on human neutrophil function. EXPERIMENTAL APPROACH: Fractions of defined molecular size were obtained from heparin by different methods and assessed for their effects on elastase release induced by formyl Met-Leu-Phe (fMLP), from neutrophils, in some cases following the priming of these cells with tumour necrosis factor-alpha (TNF-alpha). Effects of the fractions on neutrophil adhesion to interleukin-1beta (IL-beta)-stimulated human umbilical vein endothelial cells (HUVECs) were also examined. KEY RESULTS: Elastase release was inhibited by very low molecular weight fractions of heparin, with an apparent minimum chain length of 10 saccharides required for full effect. In contrast, neutrophil-endothelial adhesion was unaffected by these fractionated heparins, suggesting that certain non-anticoagulant actions of heparin may be lost by such an approach. CONCLUSIONS AND IMPLICATIONS: These data suggest that an optimum chain length of heparin possibly exists for certain non-anticoagulant actions of heparin, which may prove to be useful in the design of novel drugs with specific anti-inflammatory actions.en
dc.language.isoenen
dc.subjectTumour Necrosisen
dc.subject.meshAnticoagulants-
dc.subject.meshCell Adhesion-
dc.subject.meshChemical Fractionation-
dc.subject.meshEndothelium, Vascular-
dc.subject.meshHeparin-
dc.subject.meshHumans-
dc.subject.meshInterleukin-1beta-
dc.subject.meshMolecular Weight-
dc.subject.meshN-Formylmethionine Leucyl-Phenylalanine-
dc.subject.meshNeutrophils-
dc.subject.meshPancreatic Elastase-
dc.subject.meshStructure-Activity Relationship-
dc.subject.meshTumor Necrosis Factor-alpha-
dc.subject.meshUmbilical Veins-
dc.titleSize-fractionated heparins have differential effects on human neutrophil function in vitroen
dc.typeArticleen
dc.contributor.departmentDepartment of Pharmacology, School of Pharmacy, University of London, London, UK. rebecca.lever@pharmacy.ac.uken
dc.identifier.journalBritish Journal of Pharmacologyen
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