Print Email Facebook Twitter Inhibition of mannose receptor-mediated-clearance of tissue-type plasminogen activator (t-PA) by dextran: A new explanation for its antithrombotic effect Title Inhibition of mannose receptor-mediated-clearance of tissue-type plasminogen activator (t-PA) by dextran: A new explanation for its antithrombotic effect Author Noorman, F. Barrett-Bergshoeff, M.M. Bekkers, M. Emeis, J.J. Rijken, D.C. Gaubius Instituut TNO Publication year 1997 Abstract Dextran is used during surgery as a prophylactic agent to prevent deep venous thrombosis. Recently it has been shown that dextran increases t-PA plasma concentrations in patients. As dextran is a potential ligand for the mannose receptor, we studied whether this glucose-polymer would be able to inhibit mannose receptor-mediated clearance of t-PA. In this report we show that dextran 40 and dextran 70 were able to inhibit t-PA binding to the isolated human mannose receptor (IC50 14 and 4 mg/ml, respectively). Both glucose-polymers inhibited mannose receptor-mediated t-PA degradation by human monocyte-derived macrophages in vitro (IC50 7 and 2mg/ml, respectively). The α2- macroglobulin receptor/low density lipoprotein receptor-related protein (LRP)-mediated t-PA degradation by the macrophages was not affected by dextran. During and after a 45 min infusion of dextran 70 (Macrodex) in rats, in plasma endogenous t-PA concentrations increased to 162 ± 33% and 122 ± 35% respectively. The plasma clearance of a bolus injection of exogenous t-PA was decreased by 33 ± 9% in the same rats. We conclude that dextran inhibits mannose receptor-mediated t-PA clearance. The inhibition of tPA clearance during dextran infusion results in increased endogenous t-PA plasma concentrations. Increased t-PA concentrations present during thrombus formation are known to increase thrombus lysability. Thus the inhibition of t-PA clearance can contribute to the antithrombotic effect of dextran. Copyright © Schattauer Verlag Subject BiologyAnticoagulant agentDextranDextran 40Dextran 70Low density lipoprotein receptorMannose receptorTissue plasminogen activatorAnimal experimentBolus injectionControlled studyDeep vein thrombosisDrug infusionDrug mechanismHumanHuman cellMacrophageMaleMonocyteNonhumanPlasma clearancePriority journalProtein blood levelRatThrombogenesisAcetylgalactosamineAnimalsCells, CulturedDepression, ChemicalDextransFibrinolytic AgentsGlucoseHumansLectins, C-TypeMacrophagesMaleMannoseMannose-Binding LectinsMetabolic Clearance RateProtein BindingRatsRats, WistarReceptors, Cell SurfaceReceptors, LDLRecombinant ProteinsTissue Plasminogen Activator To reference this document use: http://resolver.tudelft.nl/uuid:5841cf7e-9ae5-4a27-9c0e-9e14352053bf DOI https://doi.org/10.1055/s-0038-1657723 TNO identifier 234071 ISSN 0340-6245 Source Thrombosis and Haemostasis, 78 (4), 1249-1254 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.