Relationship of plasma CCK to acinar cell regeneration in acute pancreatitis as studied by proliferating cell nuclear antigen

Abstract

In order to elucidate the relationship of cholecystokinin to acinar cell regeneration, the current study examined the changes in plasma cholecystokinin and immunostaining of proliferating cell nuclear antigen in the pancreas of rats with acute necrotizing pancreatitis. Proliferating cell nuclear antigen immunohistochemistry has been used to examine the proliferation of cells in several types of tissues. We compared the usefulness of proliferating cell nuclear antigen immunostaining and the incorporation of 5-bromodeoxyuridine to demonstrate acinar cell proliferation in the pancreas of rats with acute necrotizing pancreatitis. We also examined the relationship between these labeling indices and plasma cholecystokinin concentrations. The labeling index of paraformaldehyde-fixed specimens stained with proliferating cell nuclear antigen showed biphasic peaks at 12 hr and day 7. On the other hand, the methanol-fixed specimens stained with proliferating cell nuclear antigen and specimens stained with bromodeoxyuridine showed monophasic peaks in their labeling indices on day 5. There was a linear correlation (r = 0.808, P < 0.001) between the labeling index of bromodeoxyuridine and that of methanol-fixed proliferating cell nuclear antigen during the entire experimental period. During the regenerating phase, plasma cholecystokinin bioactivity showed positive correlations with the labeling index of bromodeoxyuridine and that of methanol-fixed proliferating cell nuclear antigen, r = 0.555 and 0.566, respectively (P < 0.001). Immunostaining of methanol-fixed proliferating cell nuclear antigen may be a useful tool for analyzing proliferating acinar cells. Acinar cell proliferation correlates with the bioactivity of plasma cholecystokinin during the regenerating phase of acute pancreatitis.