LOW-DOSES OF LIPOPOLYSACCHARIDE UP-REGULATE ACINAR CELL APOPTOSIS IN CERULEIN PANCREATITIS

We have reported previously that administration of a sublethal low dos e of lipopolysaccharide (LPS; 50 mu g/kg) prior to the induction of ce rulein (Cn) pancreatitis mitigates the pathological course. To clarify the mechanism, we examined apoptosis in the pancreas using the same m odel. Apoptosis was evaluated by terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end labeling (TUNEL) and transitional elect ron microscopy. LPS pretreatment at a dose of 50 mu g/kg increased rem arkably the incidence of acinar cell apoptosis in Cn pancreatitis rats compared with LPS-untreated Cn pancreatitis rats. Apoptosis was obser ved selectively in acinar cells but was not shown in endocrine cells o r ductal epithelial cells. Infiltration of inflammatory cells was scar cely observed. These acinar cells showed the characteristic morphologi cal features of apoptosis by electron microscopy. Administration of LP S at a dose of 50 mu g/kg alone caused acinar cell apoptosis but the i ncidence was much lower than that in the LPS-pretreated Cn pancreatiti s rats. The TUNEL labeling was significantly increased depending on th e dose of LPS and on the interval between the administration of LPS an d that of Cn. These results suggest that the pathological features of acute pancreatitis might be modified by the presence of nonfatal endot oxemia through the induction of acinar cell apoptosis.