Advanced

On leukocyte recruitment in colonic ischemia-reperfusion

Santén, Stefan LU (2008)
Abstract
Leukocyte recruitment is a rate-limiting step in inflammatory disease. Tissue accumulation of leukocytes is a multi-step process comprising leukocyte rolling, adhesion and transmigration across the vascular endothelium. The aim of this thesis was to investigate the mechanisms underlying ischemia-reperfusion (I/R)-induced leukocyte-endothelial cell interactions in the colon. For this purpose, intravital microscopy of the colonic microcirculation was adopted. It was found that CXC chemokine and I/R-induced leukocyte recruitment in

postcapillary venules is primarily mediated by PSGL-1 and P- but not E-selectin. Moreover, it was found that

mast cells exert a dual function in CXC chemokine and I/R-provoked colonic leukocyte... (More)
Leukocyte recruitment is a rate-limiting step in inflammatory disease. Tissue accumulation of leukocytes is a multi-step process comprising leukocyte rolling, adhesion and transmigration across the vascular endothelium. The aim of this thesis was to investigate the mechanisms underlying ischemia-reperfusion (I/R)-induced leukocyte-endothelial cell interactions in the colon. For this purpose, intravital microscopy of the colonic microcirculation was adopted. It was found that CXC chemokine and I/R-induced leukocyte recruitment in

postcapillary venules is primarily mediated by PSGL-1 and P- but not E-selectin. Moreover, it was found that

mast cells exert a dual function in CXC chemokine and I/R-provoked colonic leukocyte recruitment. On one hand, upstream chemokines trigger leukocyte recruitment via local mast cells and on the other hand, mast cells

regulate downstream formation of chemokines, which in turn provoke leukocyte recruitment. SB 239063, a

selective p38 MAPK inhibitor, has been implicated to exert a protective effect in I/R-induced tissue injury.

Herein, it was found that SB 239063 protected against I/R-induced leukocyte recruitment and mast cellgenerated

TNF-α-provoked P-selectin-mediated leukocyte adhesion. Interference with Rho-kinase signalling in I/R-induced tissue injury has indicated beneficial effects in decreasing leukocyte recruitment and proinflammatory

mediators. Fasudil and Y27632, selective Rho-kinase inhibitors, were found to decrease colonic

leukocyte recruitment, CXC chemokine and TNF-α formation and the production of oxidative stress metabolites. This thesis identifies fundamental mechanisms regulating colonic I/R-generated leukocyte recruitment, which may help to understand the pathophysiology of inflammatory disease and be of assistance in developing more specific therapies in the future. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • Björck, Martin, Institutionen för kirurgiska vetenskaper, Kirurgi, Akademiska sjukhuset, Uppsala
organization
publishing date
type
Thesis
publication status
published
subject
pages
134 pages
defense location
Aulan, CRC, ingång 72, UMAS
defense date
2008-06-04 02:45
ISBN
978-91-86059-22-4
language
English
LU publication?
yes
id
fa037adb-b455-4ce1-bf41-38c2847af42f (old id 1149089)
date added to LUP
2008-05-09 11:41:50
date last changed
2016-09-19 08:45:16
@misc{fa037adb-b455-4ce1-bf41-38c2847af42f,
  abstract     = {Leukocyte recruitment is a rate-limiting step in inflammatory disease. Tissue accumulation of leukocytes is a multi-step process comprising leukocyte rolling, adhesion and transmigration across the vascular endothelium. The aim of this thesis was to investigate the mechanisms underlying ischemia-reperfusion (I/R)-induced leukocyte-endothelial cell interactions in the colon. For this purpose, intravital microscopy of the colonic microcirculation was adopted. It was found that CXC chemokine and I/R-induced leukocyte recruitment in<br/><br>
postcapillary venules is primarily mediated by PSGL-1 and P- but not E-selectin. Moreover, it was found that<br/><br>
mast cells exert a dual function in CXC chemokine and I/R-provoked colonic leukocyte recruitment. On one hand, upstream chemokines trigger leukocyte recruitment via local mast cells and on the other hand, mast cells<br/><br>
regulate downstream formation of chemokines, which in turn provoke leukocyte recruitment. SB 239063, a<br/><br>
selective p38 MAPK inhibitor, has been implicated to exert a protective effect in I/R-induced tissue injury.<br/><br>
Herein, it was found that SB 239063 protected against I/R-induced leukocyte recruitment and mast cellgenerated<br/><br>
TNF-α-provoked P-selectin-mediated leukocyte adhesion. Interference with Rho-kinase signalling in I/R-induced tissue injury has indicated beneficial effects in decreasing leukocyte recruitment and proinflammatory<br/><br>
mediators. Fasudil and Y27632, selective Rho-kinase inhibitors, were found to decrease colonic<br/><br>
leukocyte recruitment, CXC chemokine and TNF-α formation and the production of oxidative stress metabolites. This thesis identifies fundamental mechanisms regulating colonic I/R-generated leukocyte recruitment, which may help to understand the pathophysiology of inflammatory disease and be of assistance in developing more specific therapies in the future.},
  author       = {Santén, Stefan},
  isbn         = {978-91-86059-22-4},
  language     = {eng},
  pages        = {134},
  title        = {On leukocyte recruitment in colonic ischemia-reperfusion},
  year         = {2008},
}