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Role of neutrophils in the activation of trypsinogen in severe acute pancreatitis.

Abdulla, Aree LU ; Awla, Darbaz LU ; Thorlacius, Henrik LU and Regnér, Sara LU (2011) In Journal of Leukocyte Biology 90. p.975-982
Abstract
The relationship between inflammation and proteolytic activation in pancreatitis is an unresolved issue in pancreatology. The purpose of this study was to define the influence of neutrophils on trypsinogen activation in severe AP. Pancreatitis was induced by infusion of taurocholate into the pancreatic duct in C57BL/6 mice. For neutrophil depletion, an anti-Gr-1 antibody was administered before pancreatitis induction. Administration of the anti-Gr-1 antibody reduced circulating neutrophils by 97%. Pancreatic TAP and serum amylase levels increased 2 h and 24 h after induction of pancreatitis. Neutrophil depletion reduced pancreatic TAP and serum amylase levels at 24 h but not at 2 h after pancreatitis induction. Pancreatic MPO and... (More)
The relationship between inflammation and proteolytic activation in pancreatitis is an unresolved issue in pancreatology. The purpose of this study was to define the influence of neutrophils on trypsinogen activation in severe AP. Pancreatitis was induced by infusion of taurocholate into the pancreatic duct in C57BL/6 mice. For neutrophil depletion, an anti-Gr-1 antibody was administered before pancreatitis induction. Administration of the anti-Gr-1 antibody reduced circulating neutrophils by 97%. Pancreatic TAP and serum amylase levels increased 2 h and 24 h after induction of pancreatitis. Neutrophil depletion reduced pancreatic TAP and serum amylase levels at 24 h but not at 2 h after pancreatitis induction. Pancreatic MPO and infiltration of neutrophils, as well as MIP-2 levels, were increased 24 h after taurocholate infusion. Two hours after taurocholate administration, no significant pancreatic infiltration of neutrophils was observed. Injection of the anti-Gr-1 antibody abolished MPO activity, neutrophil accumulation, and MIP-2 levels, as well as acinar cell necrosis, hemorrhage, and edema in the pancreas at 24 h. Moreover, taurocholate-provoked tissue damage and MPO activity in the lung were normalized by neutrophil depletion. Intravital fluorescence microscopy revealed a 97% reduction of leukocytes in the pancreatic microcirculation after administration of the anti-Gr-1 antibody. Our data demonstrate that initial trypsinogen activation is independent of neutrophils, whereas later activation is dependent on neutrophils in the pancreas. Neutrophils are critical in mediating pancreatic and lung tissue damage in severe AP. (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
in
Journal of Leukocyte Biology
volume
90
pages
975 - 982
publisher
Society for Leukocyte Biology
external identifiers
  • wos:000296716000015
  • pmid:21810937
  • scopus:80055081322
ISSN
1938-3673
DOI
10.1189/jlb.0411195
language
English
LU publication?
yes
id
41e324ad-700a-439f-90ee-614749f0daa6 (old id 2151585)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21810937?dopt=Abstract
date added to LUP
2011-09-04 17:01:06
date last changed
2017-10-22 04:54:27
@article{41e324ad-700a-439f-90ee-614749f0daa6,
  abstract     = {The relationship between inflammation and proteolytic activation in pancreatitis is an unresolved issue in pancreatology. The purpose of this study was to define the influence of neutrophils on trypsinogen activation in severe AP. Pancreatitis was induced by infusion of taurocholate into the pancreatic duct in C57BL/6 mice. For neutrophil depletion, an anti-Gr-1 antibody was administered before pancreatitis induction. Administration of the anti-Gr-1 antibody reduced circulating neutrophils by 97%. Pancreatic TAP and serum amylase levels increased 2 h and 24 h after induction of pancreatitis. Neutrophil depletion reduced pancreatic TAP and serum amylase levels at 24 h but not at 2 h after pancreatitis induction. Pancreatic MPO and infiltration of neutrophils, as well as MIP-2 levels, were increased 24 h after taurocholate infusion. Two hours after taurocholate administration, no significant pancreatic infiltration of neutrophils was observed. Injection of the anti-Gr-1 antibody abolished MPO activity, neutrophil accumulation, and MIP-2 levels, as well as acinar cell necrosis, hemorrhage, and edema in the pancreas at 24 h. Moreover, taurocholate-provoked tissue damage and MPO activity in the lung were normalized by neutrophil depletion. Intravital fluorescence microscopy revealed a 97% reduction of leukocytes in the pancreatic microcirculation after administration of the anti-Gr-1 antibody. Our data demonstrate that initial trypsinogen activation is independent of neutrophils, whereas later activation is dependent on neutrophils in the pancreas. Neutrophils are critical in mediating pancreatic and lung tissue damage in severe AP.},
  author       = {Abdulla, Aree and Awla, Darbaz and Thorlacius, Henrik and Regnér, Sara},
  issn         = {1938-3673},
  language     = {eng},
  pages        = {975--982},
  publisher    = {Society for Leukocyte Biology},
  series       = {Journal of Leukocyte Biology},
  title        = {Role of neutrophils in the activation of trypsinogen in severe acute pancreatitis.},
  url          = {http://dx.doi.org/10.1189/jlb.0411195},
  volume       = {90},
  year         = {2011},
}