Acinar cell membrane disruption is an early event in experimental acute pancreatitis in rats.
OBJECTIVE
To test the hypothesis that disruption of acinar cell membranes is the earliest event that takes place after the onset of acute pancreatitis.


METHODS
Cerulein and taurocholate pancreatitis were induced in rats. Furthermore, stimulation with different doses of bombesin, pilocarpine, and cerulein was performed. Five to 180 minutes after initiation of treatment, animals were killed. Disruption of cell membranes was detected by the penetration of the experimental animal's own albumin or immunoglobulin G (IgG) into acinar cells by immunocytological localization. Tissue was further analyzed by electron microscopy and electron microscopic immunostaining.


RESULTS
Animals with pancreatitis displayed significantly greater antialbumin and anti-IgG immunostaining in the cytoplasm of acinar cells and in vacuoles in comparison with controls, confirming membrane disruption. This was not detectable after stimulation with bombesin, pilocarpine, and nonsupramaximal doses of cerulein. The first changes were seen after 5 minutes of induction of pancreatitis. Results were verified by electron microscopy and electron microscopic immunohistochemistry.


CONCLUSIONS
The penetration of albumin and IgG into acinar cells indicates that wounding of their plasma membrane occurs at the onset of acute pancreatitis. Disruption of the membranes could be expected to allow the influx of calcium ions, causing massive intracellular alterations, and exit of molecules, such as enzymes from acinar cells.
Müller
Michael W
MW
Department of Surgery, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.
McNeil
Paul L
PL
Büchler
Peter
P
Ceyhan
Güralp O
GO
Wolf-Hieber
Elke
E
Adler
Guido
G
Beger
Hans G
HG
Büchler
Markus W
MW
Friess
Helmut
H
D000208:Acute Disease; D000818:Animals; D002199:Capillary Permeability; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure*; D002108:Ceruletide; D003593:Cytoplasm / Q000378:metabolism / Q000648:ultrastructure; D004195:Disease Models, Animal; D004487:Edema / Q000473:pathology; D007074:Immunoglobulin G / Q000378:metabolism; D008297:Male; D046529:Microscopy, Electron, Transmission; D016253:Microscopy, Immunoelectron / Q000379:methods; D046790:Pancreas, Exocrine / Q000098:blood supply / Q000378:metabolism / Q000648:ultrastructure*; D010195:Pancreatitis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012709:Serum Albumin / Q000378:metabolism; D013656:Taurocholic Acid; D013997:Time Factors; D014617:Vacuoles / Q000378:metabolism / Q000648:ultrastructure
D007074:Immunoglobulin G; D012709:Serum Albumin; D013656:Taurocholic Acid; D002108:Ceruletide