Effect of recombinant platelet-activating factor acetylhydrolase on two models of experimental acute pancreatitis.
OBJECTIVE
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.
Hofbauer
B
B
Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Digestive Diseases Center and Harvard Medical School, Boston, Massachusetts, USA.
Saluja
A K
AK
Bhatia
M
M
Frossard
J L
JL
Lee
H S
HS
Bhagat
L
L
Steer
M L
ML
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000208:Acute Disease; D000818:Animals; D001652:Bile Ducts; D002108:Ceruletide; D004195:Disease Models, Animal; D005765:Gastrointestinal Agents; D008026:Ligation; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008171:Lung Diseases / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D008297:Male; D009893:Opossums; D010179:Pancreas / Q000187:drug effects / Q000473:pathology; D010183:Pancreatic Ducts; D010195:Pancreatitis / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy* / Q000209:etiology; D010741:Phospholipases A / Q000627:therapeutic use*; D010972:Platelet Activating Factor / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins
D005765:Gastrointestinal Agents; D010972:Platelet Activating Factor; D011994:Recombinant Proteins; D002108:Ceruletide; D010741:Phospholipases A; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase