Ligation-induced acute pancreatitis in opossums: acinar cell necrosis in the absence of colocalization.
Acute necrotizing pancreatitis in opossums after bile and pancreatic duct ligation (BPDL) is a useful experimental corollary of gallstone-induced acute pancreatitis in humans. In experimental and human acute pancreatitis, a loss of segregation of the lysosomal enzyme cathepsin B and the zymogen proenzyme trypsinogen (colocalization) is implicated as the triggering event of disease pathogenesis, as cathepsin B can activate trypsinogen. The object of this study was to quantitate acinar cell necrosis and to study subcellular distribution of cathepsin B in BPDL-induced acute necrotizing pancreatitis in opossums. Bile and pancreatic ducts were ligated separately (no bile reflux) in four opossums while ducts were dissected in four sham controls. Opossums were killed 24 hr after operation. Three equidistant cross-sectional portions of each opossum pancreas were submitted to histologic examination. In blinded fashion, each focus of acinar cell necrosis was photographed and quantitated with digitizing morphometry. Numerical density (foci/cm2) and areal density (x10(3) micron 2/cm2) of focal acinar cell necrosis were determined. Differentially centrifuged pancreatic homogenates were assayed for cathepsin B, the lysosomal marker enzyme N-acetylglucosaminidase, and amylase. Morphometric quantitation of acinar cell necrosis confirmed development of acute necrotizing pancreatitis after 24 hr of BPDL in opossums. However, colocalization was not observed after BPDL, as evidenced by an absence of subcellular shift of cathepsin B activity (and N-acetyl-glucosaminidase activity) from the lysosome-enriched to the zymogen-enriched subcellular fraction. Amylase activity was increased in subcellular fractions after BPDL.(ABSTRACT TRUNCATED AT 250 WORDS)
Samuel
I
I
Surgical Service, Veterans Affairs Lakeside Medical Center, Chicago, Illinois.
Wilcockson
D P
DP
Regan
J P
JP
Joehl
R J
RJ
D000118:Acetylglucosaminidase / Q000378:metabolism; D000208:Acute Disease; D000681:Amylases / Q000378:metabolism; D000818:Animals; D001652:Bile Ducts; D002401:Cathepsin B / Q000378:metabolism*; D005260:Female; D008026:Ligation; D008297:Male; D009336:Necrosis; D009893:Opossums; D010183:Pancreatic Ducts; D010195:Pancreatitis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*; D013347:Subcellular Fractions / Q000378:metabolism; D014018:Tissue Distribution
D000681:Amylases; D000118:Acetylglucosaminidase; D002401:Cathepsin B