DISSOCIATION AND REASSEMBLY OF ADHERENS JUNCTIONS DURING EXPERIMENTALACUTE-PANCREATITIS

Background & Aims: The initial pathophysiological events that characte rize acute pancreatitis include the formation of pancreatic edema. An interstitial accumulation of fluid, however, is incompatible with the presence of intact intercellular junctions between acinar cells. This study examined the major components of adherens junctions, E-cadherin, alpha-catenin, beta-catenin, and actin, during the initial phase of e xperimental pancreatitis, Methods, Pancreatitis was induced in rats by 10 mu g.kg(-1).h(-1) intravenous cerulein for up to 12 hours, Adheren s junction proteins were localized by immunocytochemistry for fluoresc ence microscopy or electron microscopy, their expression was studied b y slot blot analysis, and their association was investigated by immuno precipitation and Western blot. Results: During a rapid increase of E- cadherin-encoding RNA, E-cadherin protein declined only moderately and , unlike its cytoskeletal binding partner actin, was not proteolytical ly cleaved during pancreatitis. Morphologically, E-cadherin and beta-c atenin were localized at the basolateral cell membrane from where they rapidly dissociated early in pancreatitis and to where they slowly re localized during the subsequent course. E-cadherin/beta-catenin comple xes disintegrated and reassembled competely in parallel on immunopreci pitation experiments. Conclusions: The dissociation of adherens juncti ons and the internalization, relocalization, and reassembly of their m ajor components seem to represent the critical biochemical event at ce ll-cell contacts during edema formation and resolution in acute pancre atitis.