Effect of recombinant platelet-activating factor acetylhydrolase on two models of experimental acute pancreatitis

B. Hofbauer, A. K. Saluja, M. Bhatia, J. L. Frossard, Hong Sik Lee, L. Bhagat, M. L. Steer

Research output: Contribution to journalArticle

103 Citations (Scopus)

Abstract

Background and Aims: Recent reports suggest that platelet-activating factor (PAF) plays a role in pancreatitis and pancreatitis-associated lung injury. In this study, the effects on these processes of termination of PAF action by recombinant PAF-acetylhydrolase (rPAF-AH) were investigated. Methods: Rats were given rPAF-AH and then infused with a supramaximally stimulating dose of cerulein to induce mild pancreatitis. Opossums underwent biliopancreatic duct ligation to induce severe pancreatitis, and rPAF-AH administration was begun 2 days later. Results: In mild, secretagogue- induced pancreatitis, rPAF-AH given before the cerulein reduced hyperamylasemia, acinar cell vacuolization, and pancreatic inflammation but did not alter pancreatic edema or pulmonary microvascular permeability. In severe, biliopancreatic duct ligation-induced pancreatitis, rPAF-AH delayed and reduced the extent of inflammation and acinar cell injury/necrosis and completely prevented lung injury even though the rPAF-AH administration was begun after the onset of pancreatitis. Conclusions: PAF plays an important role in the regulation of pancreatic injury but not pancreatic edema or increased pulmonary microvascular permeability in mild, secretagogue-induced pancreatitis. PAF plays a critical role in the regulation of progression of pancreatic injury and mediation of pancreatitis-associated lung injury in severe biliary pancreatitis. Amelioration of pancreatitis and prevention of pancreatitis-associated lung injury can be achieved with rPAF-AH even if treatment is begun after pancreatitis is established.

Original languageEnglish
Pages (from-to)1238-1247
Number of pages10
JournalGastroenterology
Volume115
Issue number5
DOIs
Publication statusPublished - 1998 Jan 1
Externally publishedYes

Fingerprint

Platelet Activating Factor
Pancreatitis
Theoretical Models
1-Alkyl-2-acetylglycerophosphocholine Esterase
Lung Injury
Ceruletide
Acinar Cells
Capillary Permeability
Ligation
Wounds and Injuries
Hyperamylasemia
Inflammation
Opossums
Pulmonary Edema
Edema
Necrosis

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Effect of recombinant platelet-activating factor acetylhydrolase on two models of experimental acute pancreatitis. / Hofbauer, B.; Saluja, A. K.; Bhatia, M.; Frossard, J. L.; Lee, Hong Sik; Bhagat, L.; Steer, M. L.

In: Gastroenterology, Vol. 115, No. 5, 01.01.1998, p. 1238-1247.

Research output: Contribution to journalArticle

Hofbauer, B. ; Saluja, A. K. ; Bhatia, M. ; Frossard, J. L. ; Lee, Hong Sik ; Bhagat, L. ; Steer, M. L. / Effect of recombinant platelet-activating factor acetylhydrolase on two models of experimental acute pancreatitis. In: Gastroenterology. 1998 ; Vol. 115, No. 5. pp. 1238-1247.
@article{06e23b9aa1f74a31b4ba985d61990bc8,
title = "Effect of recombinant platelet-activating factor acetylhydrolase on two models of experimental acute pancreatitis",
abstract = "Background and Aims: Recent reports suggest that platelet-activating factor (PAF) plays a role in pancreatitis and pancreatitis-associated lung injury. In this study, the effects on these processes of termination of PAF action by recombinant PAF-acetylhydrolase (rPAF-AH) were investigated. Methods: Rats were given rPAF-AH and then infused with a supramaximally stimulating dose of cerulein to induce mild pancreatitis. Opossums underwent biliopancreatic duct ligation to induce severe pancreatitis, and rPAF-AH administration was begun 2 days later. Results: In mild, secretagogue- induced pancreatitis, rPAF-AH given before the cerulein reduced hyperamylasemia, acinar cell vacuolization, and pancreatic inflammation but did not alter pancreatic edema or pulmonary microvascular permeability. In severe, biliopancreatic duct ligation-induced pancreatitis, rPAF-AH delayed and reduced the extent of inflammation and acinar cell injury/necrosis and completely prevented lung injury even though the rPAF-AH administration was begun after the onset of pancreatitis. Conclusions: PAF plays an important role in the regulation of pancreatic injury but not pancreatic edema or increased pulmonary microvascular permeability in mild, secretagogue-induced pancreatitis. PAF plays a critical role in the regulation of progression of pancreatic injury and mediation of pancreatitis-associated lung injury in severe biliary pancreatitis. Amelioration of pancreatitis and prevention of pancreatitis-associated lung injury can be achieved with rPAF-AH even if treatment is begun after pancreatitis is established.",
author = "B. Hofbauer and Saluja, {A. K.} and M. Bhatia and Frossard, {J. L.} and Lee, {Hong Sik} and L. Bhagat and Steer, {M. L.}",
year = "1998",
month = "1",
day = "1",
doi = "10.1016/S0016-5085(98)70096-4",
language = "English",
volume = "115",
pages = "1238--1247",
journal = "Gastroenterology",
issn = "0016-5085",
publisher = "W.B. Saunders Ltd",
number = "5",

}

TY - JOUR

T1 - Effect of recombinant platelet-activating factor acetylhydrolase on two models of experimental acute pancreatitis

AU - Hofbauer, B.

AU - Saluja, A. K.

AU - Bhatia, M.

AU - Frossard, J. L.

AU - Lee, Hong Sik

AU - Bhagat, L.

AU - Steer, M. L.

PY - 1998/1/1

Y1 - 1998/1/1

N2 - Background and Aims: Recent reports suggest that platelet-activating factor (PAF) plays a role in pancreatitis and pancreatitis-associated lung injury. In this study, the effects on these processes of termination of PAF action by recombinant PAF-acetylhydrolase (rPAF-AH) were investigated. Methods: Rats were given rPAF-AH and then infused with a supramaximally stimulating dose of cerulein to induce mild pancreatitis. Opossums underwent biliopancreatic duct ligation to induce severe pancreatitis, and rPAF-AH administration was begun 2 days later. Results: In mild, secretagogue- induced pancreatitis, rPAF-AH given before the cerulein reduced hyperamylasemia, acinar cell vacuolization, and pancreatic inflammation but did not alter pancreatic edema or pulmonary microvascular permeability. In severe, biliopancreatic duct ligation-induced pancreatitis, rPAF-AH delayed and reduced the extent of inflammation and acinar cell injury/necrosis and completely prevented lung injury even though the rPAF-AH administration was begun after the onset of pancreatitis. Conclusions: PAF plays an important role in the regulation of pancreatic injury but not pancreatic edema or increased pulmonary microvascular permeability in mild, secretagogue-induced pancreatitis. PAF plays a critical role in the regulation of progression of pancreatic injury and mediation of pancreatitis-associated lung injury in severe biliary pancreatitis. Amelioration of pancreatitis and prevention of pancreatitis-associated lung injury can be achieved with rPAF-AH even if treatment is begun after pancreatitis is established.

AB - Background and Aims: Recent reports suggest that platelet-activating factor (PAF) plays a role in pancreatitis and pancreatitis-associated lung injury. In this study, the effects on these processes of termination of PAF action by recombinant PAF-acetylhydrolase (rPAF-AH) were investigated. Methods: Rats were given rPAF-AH and then infused with a supramaximally stimulating dose of cerulein to induce mild pancreatitis. Opossums underwent biliopancreatic duct ligation to induce severe pancreatitis, and rPAF-AH administration was begun 2 days later. Results: In mild, secretagogue- induced pancreatitis, rPAF-AH given before the cerulein reduced hyperamylasemia, acinar cell vacuolization, and pancreatic inflammation but did not alter pancreatic edema or pulmonary microvascular permeability. In severe, biliopancreatic duct ligation-induced pancreatitis, rPAF-AH delayed and reduced the extent of inflammation and acinar cell injury/necrosis and completely prevented lung injury even though the rPAF-AH administration was begun after the onset of pancreatitis. Conclusions: PAF plays an important role in the regulation of pancreatic injury but not pancreatic edema or increased pulmonary microvascular permeability in mild, secretagogue-induced pancreatitis. PAF plays a critical role in the regulation of progression of pancreatic injury and mediation of pancreatitis-associated lung injury in severe biliary pancreatitis. Amelioration of pancreatitis and prevention of pancreatitis-associated lung injury can be achieved with rPAF-AH even if treatment is begun after pancreatitis is established.

UR - http://www.scopus.com/inward/record.url?scp=0031733230&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031733230&partnerID=8YFLogxK

U2 - 10.1016/S0016-5085(98)70096-4

DO - 10.1016/S0016-5085(98)70096-4

M3 - Article

C2 - 9797380

AN - SCOPUS:0031733230

VL - 115

SP - 1238

EP - 1247

JO - Gastroenterology

JF - Gastroenterology

SN - 0016-5085

IS - 5

ER -