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The tissue factor pathway in pneumonia
van den Boogaard, F.E.
Publication date
2015
Document Version
Final published version
Link to publication
Citation for published version (APA):
van den Boogaard, F. E. (2015). The tissue factor pathway in pneumonia.
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Floor van den Boogaard
The tissue factor
pathway in
pneumonia
The tissue factor pathway in pneumonia |
Floor van den Boogaard
The tissue factor pathway in pneumonia
Since the respiratory tract is in continuous contact with the
external environment, it is particularly prone to invading
pathogens. Pneumonia is a major cause of morbidity worldwide
with substantial mortality. Emerging bacterial resistance and
stagnation of mortality rates urge us to expand our knowledge
of the host response against bacteria, in the quest to develop
alternative treatment strategies.
Inflammation and coagulation are two important host defence
mechanisms that interact to mount an adequate immune
response against infectious agents. This thesis presents
experimental studies focused on the role of coagulation
induced by the tissue factor pathway in the immune
response against bacterial pneumonia.
The tissue factor
pathway
in pneumonia
COLOFON
The tissue factor pathway in pneumonia
Academic Thesis, University of Amsterdam, The Netherlands
ISBN: 978-94-6169-656-4
Copyright © 2015 by F. E. van den Boogaard, Amsterdam, The Netherlands
All rights reserved. No part of this thesis may be reproduced, stored, or transmitted in any form or by any means, without prior permission of the author.
Author: Florry E. van den Boogaard Cover: ontwerp & uitvoering Prisca Metz
Lay-out: Optima Grafische Communicatie, Rotterdam, The Netherlands Printed by: Optima Grafische Communicatie, Rotterdam, The Netherlands
Printing of this thesis was financially kindly supported by: Universiteit van Amsterdam,
The tissue factor pathway
in pneumonia
ACADEMISCH PROEFSCHRIFT
ter verkrijging van de graad van doctor aan de Universiteit van Amsterdam op gezag van de Rector Magnificus
prof. dr. D.C. van den Boom
ten overstaan van een door het college voor promoties ingestelde commissie, in het openbaar te verdedigen in de Agnietenkapel
op vrijdag 1 mei 2015, te 14.00 uur
door
Florry Engelina van den Boogaard
PROMOTIECOMMISSIE
Promotores: Prof. dr. T. van der Poll
Prof. dr. M. J. Schultz
Co-promotor: Dr. C. van ‘t Veer
Overige leden: Prof. dr. S. Florquin
Dr. S. E. Geerlings Prof. dr. E. de Jonge Dr. N. P. Juffermans Prof. dr. J. P. Medema Prof. dr. J. C. M. Meijers
What is a scientist after all? It is a curious man looking through a keyhole, the keyhole of nature, trying to know what's going on.
-Jacques Yves Cousteau
TABLE OF CONTENTS
Chapter 1. General introduction 9
Part I: Tissue Factor Pathway Inhibitor in pneumococcal pneumonia and lung injury
Chapter 2. Tissue Factor plays a limited role in host defense during murine
pneumococcal pneumonia
25
Chapter 3. Endogenous Tissue Factor Pathway Inhibitor has a limited effect
on host defence in murine pneumococcal pneumonia
43
Chapter 4. Recombinant Human Tissue Factor Pathway Inhibitor exerts
anti-coagulant, anti-inflammatory and antimicrobial effects in murine pneumococcal pneumonia
63
Chapter 5. Feasibility and Safety of Local Treatment with recombinant
hu-man Tissue Factor Pathway Inhibitor in a Rat Model of
Streptococ-cus pneumoniae Pneumonia
87
Chapter 6. Nebulized recombinant human Tissue Factor Pathway Inhibitor
attenuates coagulation and exhibits inflammatory and anti-bacterial properties in two models of lung injury in rats
107
Part II: Protease-Activated Receptor (PAR)-2 and endogenous activators of PAR-2 in pneumococcal pneumonia
Chapter 7. Protease-Activated Receptor-2 facilitates bacterial dissemination
during pneumococcal pneumonia
129
Chapter 8. Mast cells impair host defense during murine Streptococcus
pneu-moniae pneumonia
155
Chapter 9. Granzyme A impairs host defense during Streptococcus
pneu-moniae pneumonia
179
Part III: Platelets in pneumococcal pneumonia
Chapter 10. Thrombocytopenia impairs host defense during murine
Strepto-coccus pneumoniae pneumonia
203
Addendum
Nederlandse Samenvatting 239
Dankwoord 251
List of publications 257
PhD portfolio 259
