University of Groningen. Detoxification of LPS by alkaline phosphatase Tuin, Annemarie

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1 University of Groningen Detoxification of LPS by alkaline phosphatase Tuin, Annemarie IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from it. Please check the document version below. Document Version Publisher's PDF, also known as Version of record Publication date: 2007 Link to publication in University of Groningen/UMCG research database Citation for published version (APA): Tuin, A. (2007). Detoxification of LPS by alkaline phosphatase: application of a new concept in sepsis and inflammatory bowel disease s.n. Copyright Other than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons). Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Downloaded from the University of Groningen/UMCG research database (Pure): For technical reasons the number of authors shown on this cover page is limited to 10 maximum. Download date:

2 Detoxification of LPS by alkaline phosphatase: application of a new concept in sepsis and inflammatory bowel disease Annemarie Tuin

3 Cover: 3D structure of the enzyme alkaline phosphatase, picture obtained from The work presented in this thesis was performed at the department of Pharmacokinetics and Drug Delivery (University of Groningen), which is participating in the research school GUIDE. This research was funded by a grant from NWO, a Vernieuwingsimpuls. ISBN printed version: ISBN electronic printed version: by Annemarie Tuin All rights reserved. No part of this book may be reproduced or transmitted in any form or by any means without permission of the author and the publisher holding the copyright of the published articles. Layout: Annemarie Tuin Cover design: Annemarie Tuin, Astrid Tuin and Gildeprint drukkerijen Printed by: Gildeprint drukkerijen B.V. te Enschede

4 RIJKSUNIVERSITEIT GRONINGEN Detoxification of LPS by alkaline phosphatase: application of a new concept in sepsis and inflammatory bowel disease Proefschrift ter verkrijging van het doctoraat in de Wiskunde en Natuurwetenschappen aan de Rijksuniversiteit Groningen op gezag van de Rector Magnificus, dr. F. Zwarts, in het openbaar te verdedigen op vrijdag 11 mei 2007 om uur door Annemarie Tuin geboren op 2 mei 1978 te Veendam

5 Promotores: Prof. dr. K. Poelstra Prof. dr. D.K.F. Meijer Beoordelingscommissie: Prof. dr. H.W. Frijlink Prof. dr. J.H. Kleibeuker Prof. dr. W. Seinen

6 Een boom die te dik is om te omarmen groeit uit één klein zaadje. Een gebouw van meer dan negen verdiepingen hoog begint met een handjevol aarde. Een reis van duizend mijlen vangt aan met één enkele stap. Tao 64 als je iets heel graag wilt, kun je het bereiken. Het kan veel geduld vergen, heel veel inspanning, een echte strijd en een lange tijd; maar het is mogelijk. Zoveel vertrouwen is een vereiste voor elke onderneming, artistiek of anders. Margo Jones ( )

7 Paranimfen: Alie de Jager-Krikken Astrid Tuin Publication of this thesis was financially supported by: The University of Groningen Groningen University Institute for Drug Exploration (GUIDE) AM-Pharma Holding BV, Bunnik Harlan Nederland Schering-Plough Ferring Dr. Ir. J.H.J. Van de Laar Stichting voor Wetenschappelijk Biochemisch Onderzoek

8 Table of contents Chapter 1 Aim and outline of the thesis 1 Chapter 2 General Introduction 7 Chapter 3 On the role and fate of LPS-dephosphorylating activity 47 in the rat liver American Journal of Physiology, 2006 Feb;290(2):G Chapter 4 Exploring the regulation of endogenous alkaline 73 phosphatase levels (In preparation) Chapter 5 Alkaline phosphatase binds to the lipid A moiety of LPS 89 and reduces TNFα levels in plasma of endotoxemic mice (Submitted) Chapter 6 Oral administration of alkaline phosphatase ameliorates 113 colitis (Submitted) Chapter 7 Summary, General Discussion and Future Perspectives 137 Chapter 8 Nederlandse Samenvatting 155 Appendix I List of abbreviations 166 Selected color pictures 169 Curriculum Vitae 174 List of publications 175 Dankwoord 176 Appendix II Press Release 182

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