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

193 Pages·2017·24.15 MB·English

University of Groningen

Detoxification of LPS by alkaline phosphatase
Tuin, Annemarie
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2007
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Tuin, A. (2007). Detoxification of LPS by alkaline phosphatase: application of a new concept in sepsis and
inflammatory bowel disease. s.n.
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Download date: 17-03-2023
Detoxification of LPS by alkaline phosphatase:
application of a new concept in sepsis and
inflammatory bowel disease

Annemarie Tuin
Cover: 3D structure of the enzyme alkaline phosphatase, picture obtained from
www.imbb.forth.gr/people/bouriotis/images/photo1.gif.

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: 9789036729932
ISBN electronic printed version: 9789036729949

 2007 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
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 14.45 uur

door

Annemarie Tuin

geboren op 2 mei 1978
te Veendam
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
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 ver-
trouwen is een vereiste voor
elke onderneming, artistiek
of anders.

Margo Jones (1913-1955)
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
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):G377-85

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

Chapter 1
Aim and outline of the thesis