LUMINAL ENDOCYTOSIS AND INTRACELLULAR TARGETING BY ACINAR-CELLS DURING EARLY BILIARY PANCREATITIS IN THE OPOSSUM

Cell necrosis in acute experimental pancreatitis is preceded by a redi stribution of digestive enzymes into a lysosomal subcellular compartme nt. We have investigated whether endocytosis from the acinar cell lume n might contribute to this disturbance of intracellular compartmentati on. In an animal model of pancreatitis involving pancreatic bile duct ligation in opossums, we have studied in vivo endocytosis of dextran 4 0 and [C-14] dextran 70, cationized ferritin, and horseradish peroxida se from the apical surface of acinar cells before the onset of necrosi s. Marker solutions mere instilled into the pancreatic duct of anesthe tized animals at physiological pressure. Tissue samples obtained at in tervals of up to 60 min after instillation of markers were studied by electron microscopy and electron microscope autoradiography, All marke rs were taken up by acinar cells in control animals and in animals wit h obstructed pancreatic bile ducts. Markers for membrane-mediated endo cytosis (cationated ferritin and horseradish peroxidase) were transpor ted to lysosomes in both groups. In contrast, the fluid-phase tracer d extran was transported to the secretory pathway in controls but to lys osomes after duct ligation, Since dextran and luminally present secret ory proteins can be expected to follow the same route after endocytosi s, our findings suggest that altered intracellular targeting of endocy tosed proteases might be one mechanism by which digestive zymogens rea ch an intracellular compartment in which premature activation can occu r. This phenomenon may be a critical and early event in the pathogenes is of biliary pancreatitis.