Lymphocyte function antigen-1 regulates neutrophil recruitment and tissue damage in acute pancreatitis.
Awla, Darbaz LU ; Abdulla, Aree LU ; Zhang, Su LU ; Roller, Jonas ; Menger, Michael ; Regnér, Sara LU
and Thorlacius, Henrik
LU
(2011)
In British Journal of Pharmacology
163.
p.413-423
- Abstract
- Background and purpose: Leucocyte infiltration is a rate-limiting step in the pathophysiology of acute pancreatitis (AP) although the adhesive mechanisms supporting leucocyte-endothelium interactions in the pancreas remain elusive. The aim of this study was to define the role of lymphocyte function antigen-1 (LFA-1) in regulating neutrophil-endothelium interactions and tissue damage in severe AP. Experimental approach: Pancreatitis was induced by retrograde infusion of sodium taurocholate into the pancreatic duct in mice. LFA-1 gene-targeted mice and an antibody directed against LFA-1 were used to define the role of LFA-1. Key results: Taurocholate challenge caused a clear-cut increase in serum amylase, neutrophil infiltration, CXCL2... (More)
- Background and purpose: Leucocyte infiltration is a rate-limiting step in the pathophysiology of acute pancreatitis (AP) although the adhesive mechanisms supporting leucocyte-endothelium interactions in the pancreas remain elusive. The aim of this study was to define the role of lymphocyte function antigen-1 (LFA-1) in regulating neutrophil-endothelium interactions and tissue damage in severe AP. Experimental approach: Pancreatitis was induced by retrograde infusion of sodium taurocholate into the pancreatic duct in mice. LFA-1 gene-targeted mice and an antibody directed against LFA-1 were used to define the role of LFA-1. Key results: Taurocholate challenge caused a clear-cut increase in serum amylase, neutrophil infiltration, CXCL2 (macrophage inflammatory protein-2) formation, trypsinogen activation and tissue damage in the pancreas. Inhibition of LFA-1 function markedly reduced taurocholate-induced amylase levels, accumulation of neutrophils, production of CXC chemokines and tissue damage in the pancreas. Notably, intravital microscopy revealed that inhibition of LFA-1 abolished taurocholate-induced leucocyte adhesion in postcapillray venules of the pancreas. In addition, pulmonary infiltration of neutrophils was attenuated by inhibition of LFA-1 in mice challenged with taurocholate. However, interference with LFA-1 had no effect on taurocholate-induced activation of trypsinogen in the pancreas. Conclusions and Implications: Our novel data suggest that LFA-1 plays a key role in regulating neutrophil recruitment, CXCL2 formation and tissue injury in the pancreas. Moreover, these results suggest that LFA-1-mediated inflammation is a downstream component of trypsinogen activation in the pathophysiology of AP. Thus, we conclude that targeting LFA-1 may be a useful approach to protect against pathological inflammation in the pancreas. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1777347
- author
- Awla, Darbaz
LU
; Abdulla, Aree
LU
; Zhang, Su
LU
; Roller, Jonas
; Menger, Michael
; Regnér, Sara
LU
and Thorlacius, Henrik
LU
- organization
- publishing date
- 2011
- type
- Contribution to journal
- publication status
- published
- subject
- in
- British Journal of Pharmacology
- volume
- 163
- pages
- 413 - 423
- publisher
- Wiley
- external identifiers
-
- wos:000289642600018
- pmid:21244370
- scopus:79954530675
- pmid:21244370
- ISSN
- 1476-5381
- DOI
- 10.1111/j.1476-5381.2011.01225.x
- language
- English
- LU publication?
- yes
- id
- 9d11cab5-aee4-4be1-bd92-3d098e6208ed (old id 1777347)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/21244370?dopt=Abstract
- date added to LUP
- 2016-04-04 09:28:40
- date last changed
- 2022-03-31 03:00:55
@article{9d11cab5-aee4-4be1-bd92-3d098e6208ed,
abstract = {{Background and purpose: Leucocyte infiltration is a rate-limiting step in the pathophysiology of acute pancreatitis (AP) although the adhesive mechanisms supporting leucocyte-endothelium interactions in the pancreas remain elusive. The aim of this study was to define the role of lymphocyte function antigen-1 (LFA-1) in regulating neutrophil-endothelium interactions and tissue damage in severe AP. Experimental approach: Pancreatitis was induced by retrograde infusion of sodium taurocholate into the pancreatic duct in mice. LFA-1 gene-targeted mice and an antibody directed against LFA-1 were used to define the role of LFA-1. Key results: Taurocholate challenge caused a clear-cut increase in serum amylase, neutrophil infiltration, CXCL2 (macrophage inflammatory protein-2) formation, trypsinogen activation and tissue damage in the pancreas. Inhibition of LFA-1 function markedly reduced taurocholate-induced amylase levels, accumulation of neutrophils, production of CXC chemokines and tissue damage in the pancreas. Notably, intravital microscopy revealed that inhibition of LFA-1 abolished taurocholate-induced leucocyte adhesion in postcapillray venules of the pancreas. In addition, pulmonary infiltration of neutrophils was attenuated by inhibition of LFA-1 in mice challenged with taurocholate. However, interference with LFA-1 had no effect on taurocholate-induced activation of trypsinogen in the pancreas. Conclusions and Implications: Our novel data suggest that LFA-1 plays a key role in regulating neutrophil recruitment, CXCL2 formation and tissue injury in the pancreas. Moreover, these results suggest that LFA-1-mediated inflammation is a downstream component of trypsinogen activation in the pathophysiology of AP. Thus, we conclude that targeting LFA-1 may be a useful approach to protect against pathological inflammation in the pancreas.}},
author = {{Awla, Darbaz and Abdulla, Aree and Zhang, Su and Roller, Jonas and Menger, Michael and Regnér, Sara and Thorlacius, Henrik}},
issn = {{1476-5381}},
language = {{eng}},
pages = {{413--423}},
publisher = {{Wiley}},
series = {{British Journal of Pharmacology}},
title = {{Lymphocyte function antigen-1 regulates neutrophil recruitment and tissue damage in acute pancreatitis.}},
url = {{http://dx.doi.org/10.1111/j.1476-5381.2011.01225.x}},
doi = {{10.1111/j.1476-5381.2011.01225.x}},
volume = {{163}},
year = {{2011}},
}