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Filling the gaps
The endothelium in regulating vascular leakage and leukocyte extravasation
Schimmel, L.
Publication date
2018
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Citation for published version (APA):
Schimmel, L. (2018). Filling the gaps: The endothelium in regulating vascular leakage and
leukocyte extravasation.
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Filling the gaps
The endothelium in regulating
vascular leakage and leukocyte
extravasation
Lilian Schimmel
Filling the gaps: The endothelium in regulating vascular leakage and leukocyte extravasation Lilian Schimmel
Uitnodiging
voor het bijwonen van de
openbare verdediging van
het proefschrift
Filling the gaps: The
endothelium in regulating
vascular leakage and
leukocyte extravasation
door
Lilian Schimmel
Vrijdag 15 juni 2018
om 14:00 uur
Agnietenkapel
Oudezijds Voorburgwal
231, Amsterdam
Na afloop bent u van
harte uitgenodigd voor de
receptie ter plaatse
Lilian Schimmel
lilianschimmel90@gmail.comparanimfen
Mark Hoogenboezem
m.hoogenboezem@sanquin.nlSimon Tol
s.tol@sanquin.nl Cover_Lilian Schimmel.indd 1 26-4-2018 19:49:25Filling the gaps
The endothelium in regulating
vascular leakage and leukocyte
extravasation
ISBN: 978-94-6233-962-0
The studies performed in this thesis were performed at the Department of Plasma Proteins, Molecular Cell Biology Lab, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of
Amsterdam, The Netherlands and financially supported by the Rembrandt Institute of Cardiovascular Science.
Printing of this thesis was financially supported by Sanquin Research and Vasculitis Stichting.
Photo cover by Willem Schimmel Layout by Ivar Noordstra
Printed by Gildeprint © 2018 by Lilian Schimmel All rights reserved
Filling the gaps
The endothelium in regulating vascular leakage and leukocyte extravasation
ACADEMISCH PROEFSCHRIFT
ter verkrijging van de graad van doctor aan de Universiteit van Amsterdam op gezag van de Rector Magnificus
prof. dr. ir. K.I.J. Maex
ten overstaan van een door het College voor Promoties ingestelde commissie, in het openbaar te verdedigen in de Agnietenkapel
op vrijdag 15 juni 2018, te 14.00 uur
door
Lilian Schimmel
Promotiecommissie:
Promotor: prof. dr. P.L. Hordijk Universiteit van Amsterdam Copromotores: dr. J.D. van Buul Universiteit van Amsterdam
dr. V. de Waard AMC-UvA
Overige leden: prof. dr. T.W.J. Gadella Universiteit van Amsterdam prof. dr. C.J.M de Vries Universiteit van Amsterdam prof. dr. E. Lutgens Universiteit van Amsterdam dr. J.C. Sluimer Maastricht University
prof. dr. A. Sonnenberg Leiden Academic Centre for
Drug Research
“All we know is still infinitely less than all that remains unknown”
Table of contents
8 26 52 106 124 148 182 208 228 231 232 234 235 General introductionLeukocyte transendothelial migration: A local affair F-actin rich contractile endothelial pores prevent vascular leakage during leukocyte diapedesis through local RhoA signaling
Endothelial RhoB and RhoC are dispensable for leukocyte diapedesis and for maintaining vascular integrity during diapedesis
The Rho-GEFs FGD5 and Tuba differentially regulate the small GTPase Cdc42 to control leukocyte
extravasation and vascular permeability
Stiffness-induced endothelial DLC-1 expression forces leukocyte spreading through stabilization of the ICAM-1 adhesome
Rac1 activation by the endothelial GEF Tiam1 marks sites for leukocyte diapedesis through guiding junctional membrane ruffles
Summary and concluding remarks Nederlandse samenvatting Curriculum Vitae Portfolio Publication list Dankwoord Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Chapter 7 Chapter 8 Addendum