P-selectin mediates neutrophil rolling and recruitment in acute pancreatitis.
Hartman Magnusson, Hannes LU ; Abdulla, Aree LU ; Awla, Darbaz LU ; Lindkvist, Björn LU ; Jeppsson, Bengt LU ; Thorlacius, Henrik LU and Regnér, Sara LU
(2012)
In British Journal of Surgery
99.
p.246-255
- Abstract
- BACKGROUND: The adhesive mechanisms regulating leucocyte-endothelium interactions in the pancreas remain elusive, but selectins may play a role. This study examined the molecular mechanisms mediating leucocyte rolling along the endothelium in the pancreas and the therapeutic potential of targeting the rolling adhesive interaction in acute pancreatitis (AP). METHODS: Pancreatitis was induced by retrograde infusion of 5 per cent sodium taurocholate into the pancreatic duct, repeated intraperitoneal administration of caerulein (50 µg/kg) or intraperitoneal administration of L-arginine (4 g/kg) in C57BL/6 mice. A control and a monoclonal antibody against P-selectin were administered before and after induction of AP. Serum and tissue were... (More)
- BACKGROUND: The adhesive mechanisms regulating leucocyte-endothelium interactions in the pancreas remain elusive, but selectins may play a role. This study examined the molecular mechanisms mediating leucocyte rolling along the endothelium in the pancreas and the therapeutic potential of targeting the rolling adhesive interaction in acute pancreatitis (AP). METHODS: Pancreatitis was induced by retrograde infusion of 5 per cent sodium taurocholate into the pancreatic duct, repeated intraperitoneal administration of caerulein (50 µg/kg) or intraperitoneal administration of L-arginine (4 g/kg) in C57BL/6 mice. A control and a monoclonal antibody against P-selectin were administered before and after induction of AP. Serum and tissue were sampled to assess the severity of pancreatitis, and intravital microscopy was used to study leucocyte rolling. RESULTS: Taurocholate infusion into the pancreatic duct increased the serum level of trypsinogen, trypsinogen activation, pancreatic neutrophil infiltration, macrophage inflammatory protein (MIP) 2 formation and tissue damage. Immunoneutralization of P-selectin decreased the taurocholate-induced increase in serum trypsinogen (median (range) 17·35 (12·20-30·00) versus 1·55 (0·60-15·70) µg/l; P = 0·017), neutrophil accumulation (4·00 (0·75-4·00) versus 0·63 (0-3·25); P = 0·002) and tissue damage, but had no effect on MIP-2 production (14·08 (1·68-33·38) versus 3·70 (0·55-51·80) pg/mg; P = 0·195) or serum trypsinogen activating peptide level (1·10 (0·60-1·60) versus 0·45 (0-1·80) µg/l; P = 0·069). Intravital fluorescence microscopy revealed that anti-P-selectin antibody inhibited leucocyte rolling completely in postcapillary venules of the inflamed pancreas. CONCLUSION: Inhibition of P-selectin protected against pancreatic tissue injury in experimental pancreatitis. Targeting P-selectin may be an effective strategy to ameliorate inflammation in AP. Copyright © 2011 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/2220498
- author
- Hartman Magnusson, Hannes
LU
; Abdulla, Aree
LU
; Awla, Darbaz
LU
; Lindkvist, Björn
LU
; Jeppsson, Bengt
LU
; Thorlacius, Henrik
LU
and Regnér, Sara
LU
- organization
- publishing date
- 2012
- type
- Contribution to journal
- publication status
- published
- subject
- in
- British Journal of Surgery
- volume
- 99
- pages
- 246 - 255
- publisher
- Oxford University Press
- external identifiers
-
- wos:000303148200016
- pmid:22109627
- scopus:84855697952
- ISSN
- 1365-2168
- DOI
- 10.1002/bjs.7775
- language
- English
- LU publication?
- yes
- id
- 9fcdbe5f-7c90-4be3-ab06-7b55af5a61d0 (old id 2220498)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/22109627?dopt=Abstract
- date added to LUP
- 2016-04-04 08:06:53
- date last changed
- 2022-03-30 23:12:04
@article{9fcdbe5f-7c90-4be3-ab06-7b55af5a61d0,
abstract = {{BACKGROUND: The adhesive mechanisms regulating leucocyte-endothelium interactions in the pancreas remain elusive, but selectins may play a role. This study examined the molecular mechanisms mediating leucocyte rolling along the endothelium in the pancreas and the therapeutic potential of targeting the rolling adhesive interaction in acute pancreatitis (AP). METHODS: Pancreatitis was induced by retrograde infusion of 5 per cent sodium taurocholate into the pancreatic duct, repeated intraperitoneal administration of caerulein (50 µg/kg) or intraperitoneal administration of L-arginine (4 g/kg) in C57BL/6 mice. A control and a monoclonal antibody against P-selectin were administered before and after induction of AP. Serum and tissue were sampled to assess the severity of pancreatitis, and intravital microscopy was used to study leucocyte rolling. RESULTS: Taurocholate infusion into the pancreatic duct increased the serum level of trypsinogen, trypsinogen activation, pancreatic neutrophil infiltration, macrophage inflammatory protein (MIP) 2 formation and tissue damage. Immunoneutralization of P-selectin decreased the taurocholate-induced increase in serum trypsinogen (median (range) 17·35 (12·20-30·00) versus 1·55 (0·60-15·70) µg/l; P = 0·017), neutrophil accumulation (4·00 (0·75-4·00) versus 0·63 (0-3·25); P = 0·002) and tissue damage, but had no effect on MIP-2 production (14·08 (1·68-33·38) versus 3·70 (0·55-51·80) pg/mg; P = 0·195) or serum trypsinogen activating peptide level (1·10 (0·60-1·60) versus 0·45 (0-1·80) µg/l; P = 0·069). Intravital fluorescence microscopy revealed that anti-P-selectin antibody inhibited leucocyte rolling completely in postcapillary venules of the inflamed pancreas. CONCLUSION: Inhibition of P-selectin protected against pancreatic tissue injury in experimental pancreatitis. Targeting P-selectin may be an effective strategy to ameliorate inflammation in AP. Copyright © 2011 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.}},
author = {{Hartman Magnusson, Hannes and Abdulla, Aree and Awla, Darbaz and Lindkvist, Björn and Jeppsson, Bengt and Thorlacius, Henrik and Regnér, Sara}},
issn = {{1365-2168}},
language = {{eng}},
pages = {{246--255}},
publisher = {{Oxford University Press}},
series = {{British Journal of Surgery}},
title = {{P-selectin mediates neutrophil rolling and recruitment in acute pancreatitis.}},
url = {{http://dx.doi.org/10.1002/bjs.7775}},
doi = {{10.1002/bjs.7775}},
volume = {{99}},
year = {{2012}},
}