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Human thrombin-derived host defense peptides inhibit neutrophil recruitment and tissue injury in severe acute pancreatitis.

Merza, Mohammed LU ; Rahman, Milladur LU ; Zhang, Songen LU ; Hwaiz, Rundk LU ; Regnér, Sara LU ; Schmidtchen, Artur LU and Thorlacius, Henrik LU (2014) In American Journal of Physiology: Gastrointestinal and Liver Physiology 307(9). p.914-921
Abstract
Severe acute pancreatitis (AP) is characterized by leukocyte infiltration and tissue injury. Herein, we wanted to examine the potential effects of thrombin-derived host defense peptides (TDPs) in severe AP. Pancreatitis was provoked by infusion of taurocholate into the pancreatic duct or by intraperitoneal administration of L-arginine in C57BL/6 mice. Animals were treated with the TDPs GKY20 and GKY25 or a control peptide WFF25 30 min before induction of AP. TDPs reduced blood amylase levels, neutrophil infiltration, hemorrhage, necrosis and edema formation in the inflamed pancreas. Treatment with TDPs markedly attenuated the taurocholate-induced increase in plasma levels of CXCL2 and interleukin-6. Moreover, administration of TDPs... (More)
Severe acute pancreatitis (AP) is characterized by leukocyte infiltration and tissue injury. Herein, we wanted to examine the potential effects of thrombin-derived host defense peptides (TDPs) in severe AP. Pancreatitis was provoked by infusion of taurocholate into the pancreatic duct or by intraperitoneal administration of L-arginine in C57BL/6 mice. Animals were treated with the TDPs GKY20 and GKY25 or a control peptide WFF25 30 min before induction of AP. TDPs reduced blood amylase levels, neutrophil infiltration, hemorrhage, necrosis and edema formation in the inflamed pancreas. Treatment with TDPs markedly attenuated the taurocholate-induced increase in plasma levels of CXCL2 and interleukin-6. Moreover, administration of TDPs decreased histone 3, histone 4 and MPO levels in the pancreas in response to taurocholate challenge. Interestingly, administration of TDPs abolished neutrophil expression of Mac-1 in mice with pancreatitis. In addition, TDPs inhibited CXCL2-induced chemotaxis of isolated neutrophils in vitro. Fluorescent-labeled TDP was found to directly bind to isolated neutrophils. Finally, a beneficial effect of TDPs was confirmed in L-arginine-induced pancreatitis. Our novel results demonstrate that TDPs exert protective effects against pathological inflammation and tissue damage in AP. These novel findings suggest that TDPs might be useful in the management of patients with severe AP. (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
in
American Journal of Physiology: Gastrointestinal and Liver Physiology
volume
307
issue
9
pages
914 - 921
publisher
American Physiological Society
external identifiers
  • pmid:25214403
  • wos:000344995500005
  • scopus:84908360947
ISSN
1522-1547
DOI
10.1152/ajpgi.00237.2014
language
English
LU publication?
yes
id
ff45d544-cb53-4722-a968-5ceefa8df278 (old id 4691812)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/25214403?dopt=Abstract
date added to LUP
2014-10-05 20:18:02
date last changed
2017-10-01 03:02:28
@article{ff45d544-cb53-4722-a968-5ceefa8df278,
  abstract     = {Severe acute pancreatitis (AP) is characterized by leukocyte infiltration and tissue injury. Herein, we wanted to examine the potential effects of thrombin-derived host defense peptides (TDPs) in severe AP. Pancreatitis was provoked by infusion of taurocholate into the pancreatic duct or by intraperitoneal administration of L-arginine in C57BL/6 mice. Animals were treated with the TDPs GKY20 and GKY25 or a control peptide WFF25 30 min before induction of AP. TDPs reduced blood amylase levels, neutrophil infiltration, hemorrhage, necrosis and edema formation in the inflamed pancreas. Treatment with TDPs markedly attenuated the taurocholate-induced increase in plasma levels of CXCL2 and interleukin-6. Moreover, administration of TDPs decreased histone 3, histone 4 and MPO levels in the pancreas in response to taurocholate challenge. Interestingly, administration of TDPs abolished neutrophil expression of Mac-1 in mice with pancreatitis. In addition, TDPs inhibited CXCL2-induced chemotaxis of isolated neutrophils in vitro. Fluorescent-labeled TDP was found to directly bind to isolated neutrophils. Finally, a beneficial effect of TDPs was confirmed in L-arginine-induced pancreatitis. Our novel results demonstrate that TDPs exert protective effects against pathological inflammation and tissue damage in AP. These novel findings suggest that TDPs might be useful in the management of patients with severe AP.},
  author       = {Merza, Mohammed and Rahman, Milladur and Zhang, Songen and Hwaiz, Rundk and Regnér, Sara and Schmidtchen, Artur and Thorlacius, Henrik},
  issn         = {1522-1547},
  language     = {eng},
  number       = {9},
  pages        = {914--921},
  publisher    = {American Physiological Society},
  series       = {American Journal of Physiology: Gastrointestinal and Liver Physiology},
  title        = {Human thrombin-derived host defense peptides inhibit neutrophil recruitment and tissue injury in severe acute pancreatitis.},
  url          = {http://dx.doi.org/10.1152/ajpgi.00237.2014},
  volume       = {307},
  year         = {2014},
}