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Platelets regulate P-selectin expression and leukocyte rolling in inflamed venules of the pancreas

Abdulla, Aree LU ; Awla, Darbaz LU ; Hartman Magnusson, Hannes LU ; Weiber, Haan; Jeppsson, Bengt LU ; Regnér, Sara LU and Thorlacius, Henrik LU (2012) In European Journal of Pharmacology 682(1-3). p.153-160
Abstract
Recent data suggest that platelets regulate inflammatory changes and tissue damage in acute pancreatitis although the role of platelets in leukocyte-endothelium interactions in the pancreatic microcirculation is not known. The aim of this study was to define the impact of platelets on leukocyte rolling and adhesion in acute pancreatitis. Acute pancreatitis was induced in C57BL/6 mice by caerulein challenge. Mice were treated with an a anti-GP1b alpha (CD42b) antibody, which depletes platelets, or a control antibody before caerulein. Leukocyte rolling and adhesion were determined by the use of intravital fluorescence microscopy 18 h after the last dose of caerulein. In separate experiments, leukocyte-endothelium interactions were determined... (More)
Recent data suggest that platelets regulate inflammatory changes and tissue damage in acute pancreatitis although the role of platelets in leukocyte-endothelium interactions in the pancreatic microcirculation is not known. The aim of this study was to define the impact of platelets on leukocyte rolling and adhesion in acute pancreatitis. Acute pancreatitis was induced in C57BL/6 mice by caerulein challenge. Mice were treated with an a anti-GP1b alpha (CD42b) antibody, which depletes platelets, or a control antibody before caerulein. Leukocyte rolling and adhesion were determined by the use of intravital fluorescence microscopy 18 h after the last dose of caerulein. In separate experiments, leukocyte-endothelium interactions were determined before and after administration of an anti-P-selectin, anti-PSGL-1 and a control antibody in mice with caerulein pancreatitis. Circulating platelet-neutrophil aggregates and pancreatic P-selectin mRNA were quantified 1 and 6 h respectively after caerulein challenge. Caerulein administration increased leukocyte and platelet interactions in the pancreatic microvasculature, increased tissue damage and expression of P-selectin mRNA in the pancreas as well as platelet-neutrophil complexes in the circulation. Notably, platelet depletion markedly reduced caerulein-provoked leukocyte rolling and adhesion in postcapillary venules. Interestingly, depletion of platelets significantly decreased caerulein-induced gene expression of P-selectin in the pancreas. Moreover, immunoneutralization of P-selectin and PSGL-1 abolished leukocyte rolling in the pancreatic venules triggered by caerulein. Our novel findings demonstrate that platelets regulate leukocyte rolling in acute pancreatitis via induction of P-selectin, which was critical in supporting leukocyte rolling in inflamed venules of the pancreas. (C) 2012 Elsevier B.V. All rights reserved. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Adhesion molecule, Endothelium, Inflammation, Intravital fluorescence, microscopy, Pancreas
in
European Journal of Pharmacology
volume
682
issue
1-3
pages
153 - 160
publisher
Elsevier
external identifiers
  • wos:000302982400021
  • scopus:84859104988
ISSN
1879-0712
DOI
10.1016/j.ejphar.2012.02.014
language
English
LU publication?
yes
id
aa2cdce7-4db2-4879-bd05-0761fde38c0a (old id 2570852)
date added to LUP
2012-06-01 08:52:49
date last changed
2017-04-30 04:54:22
@article{aa2cdce7-4db2-4879-bd05-0761fde38c0a,
  abstract     = {Recent data suggest that platelets regulate inflammatory changes and tissue damage in acute pancreatitis although the role of platelets in leukocyte-endothelium interactions in the pancreatic microcirculation is not known. The aim of this study was to define the impact of platelets on leukocyte rolling and adhesion in acute pancreatitis. Acute pancreatitis was induced in C57BL/6 mice by caerulein challenge. Mice were treated with an a anti-GP1b alpha (CD42b) antibody, which depletes platelets, or a control antibody before caerulein. Leukocyte rolling and adhesion were determined by the use of intravital fluorescence microscopy 18 h after the last dose of caerulein. In separate experiments, leukocyte-endothelium interactions were determined before and after administration of an anti-P-selectin, anti-PSGL-1 and a control antibody in mice with caerulein pancreatitis. Circulating platelet-neutrophil aggregates and pancreatic P-selectin mRNA were quantified 1 and 6 h respectively after caerulein challenge. Caerulein administration increased leukocyte and platelet interactions in the pancreatic microvasculature, increased tissue damage and expression of P-selectin mRNA in the pancreas as well as platelet-neutrophil complexes in the circulation. Notably, platelet depletion markedly reduced caerulein-provoked leukocyte rolling and adhesion in postcapillary venules. Interestingly, depletion of platelets significantly decreased caerulein-induced gene expression of P-selectin in the pancreas. Moreover, immunoneutralization of P-selectin and PSGL-1 abolished leukocyte rolling in the pancreatic venules triggered by caerulein. Our novel findings demonstrate that platelets regulate leukocyte rolling in acute pancreatitis via induction of P-selectin, which was critical in supporting leukocyte rolling in inflamed venules of the pancreas. (C) 2012 Elsevier B.V. All rights reserved.},
  author       = {Abdulla, Aree and Awla, Darbaz and Hartman Magnusson, Hannes and Weiber, Haan and Jeppsson, Bengt and Regnér, Sara and Thorlacius, Henrik},
  issn         = {1879-0712},
  keyword      = {Adhesion molecule,Endothelium,Inflammation,Intravital fluorescence,microscopy,Pancreas},
  language     = {eng},
  number       = {1-3},
  pages        = {153--160},
  publisher    = {Elsevier},
  series       = {European Journal of Pharmacology},
  title        = {Platelets regulate P-selectin expression and leukocyte rolling in inflamed venules of the pancreas},
  url          = {http://dx.doi.org/10.1016/j.ejphar.2012.02.014},
  volume       = {682},
  year         = {2012},
}