Degradation of zymogen granules by lysosomes in cultured pancreatic explants

Pancreatic explants from Syrian hamsters were maintained in culture for determination of the fate of the zymogen granules in the acinar cells. By 6 hours of culture the zymogen granule matrix in many cells becomes nonhomogeneous, and electron-lucent spaces appear. Autoradiography performed 48 hours after pulse labeling shows that several of the altered zymogen granules contain radioactively labeled proteins. Hence these altered granules are mature zymogen granules undergoing regression. Ultrastructural analyses indicate that the zymogen granules are degraded intracellularly in the lysosomes by autophagy, by direct fusion between the lysosomes and the zymogen granules, as well as by engulfment of intact zymogen granules by the lysosomes. Budding of cytoplasm into zymogen granules is also frequently observed. Acid phosphatase histochemistry and anti-amylase immunohistochemistry were used for demonstration of presence of hydrolases and of secretory material in the degenerating zymogen granules. Cycloheximide and low temperature inhibit the degradation of zymogen granules and enhance the short-term viability of the explant. Secretagogues stimulate secretion but have little or no effect on the degradation of zymogen granules or on explant viability. The lysosomes participate in the intracellular degradation of zymogen granules in acinar cells of pancreatic explants. The induction of these lysosomal catabolic processes correlates with the structural alteration of pancreatic acinar cells. The intracellular degradation of secretory membranes and products by the lysosomes may play a role in the adaptation of pancreatic acinar cells to injury.