USE OF ISOLATED ACINAR-CELLS TO CHARACTER IZE THE MECHANISMS THAT LEAD TO CELL-DAMAGE IN ACUTE-PANCREATITIS

Due to the complexity of interacting organ systems, in vivo the interp retation of results obtained from whole-animal experiments of acute pa ncreatitis remains difficult. To enlighten cause-and-effect-relationsh ips, functional isolated parts of the pancreas are applied increasingl y in research into the pathogenesis of the disease, therefore. By mean s of a collagenase digestion technique, intact acinar cells from norma l as well as from pretreated rat pancreas could reproducibly be obtain ed in high yield. Animals were pretreated in situ by induction of eith er mesenteric ischemia/reperfusion; juice edema, or acute pancreatitis (AP). Pancreatic acinar cells isolated from these pretreated rats con sumed oxygen at comparable rates under resting conditions throughout a ll experimental groups. A reduced stress capacity of cell respiration as well as a preterm decline in short-term culture was observed in the cells of the AP group, however. These results demonstrate that the in duction of AP has found its reflection within the acinar cells themsel ves. Interestingly, these effects were not clouded by the isolation pr ocedure. The manner of in-situ pretreatment of the respective animal p roved to be decisive for later viability of isolated acinar cells in s hort-term culture. Uncoupling of oxidative phosphorylation by 2,4-dimi trophenol (DNP) lead to an accelerated decline of the acinar cells in all groups. The intactness of cellular energy metabolism seems to play a crucial role in maintaining cellular integrity, therefore. In addit ional experiments in vitro, the intracellularly mediated cell damage b y DNP was compared with one induced from the extracellular environment of isolated cells by antibodies directed against cell surface antigen s plus complement. These immunological agents lead to acinar cell dama ge in dependence on their concentration. The kinetics of this damage d iffered completely from that induced by the intracellularly acting DNP , however. The in vitro follow-up of cells decline proved to be a simp le but suitable parameter for characterization of the effects of exper imental AP at the cellular level and the analysis of the damaging pote ntial of noxious agents on intact acinar cells as well.