title: Cell wounding in early experimental acute pancreatitis.
abstract: It is well established that damage to the outer membrane of cells is a common phenomenon allowing abnormal transmission of substances into the cytosol. Penetration of albumin into acinar cells has been detected in experimental acute pancreatitis, raising the possibility that membrane damage is a very early event, potentially representing the first changes leading to pancreatitis. To determine if direct damage to the cell membrane is a key factor during induction of acute pancreatitis, thus altering the balance of extra- and intracellular substances, fluorescein-dextran was administered with supramaximal doses of caerulein via the jugular vein or by injection directly into the pancreas. This tracer rapidly penetrates into cells. Two patterns of tracer penetration are observed: cytosolic and vesicular/vacuolar. Fluorescein-dextran administered intravenously with caerulein penetrates into the cytosol of acinar cells within 10 min. Strong cytoplasmic fluorescence occurs within 5 min after direct injection. It may be concluded that supramaximal caerulein, administered in vivo, damages the cell membrane of acinar cells, allowing large molecules to enter the cytosol. Thus Ca(2+) and other substances may enter the cells in abnormally high concentrations, initiating the cellular changes characteristic of pancreatitis. The results raise the question whether membrane wounding may play a role in the initiation of human pancreatitis.
authors.affiliation: Department of General Surgery, University of Heidelberg, Germany. hodney@msn.com
authors.forename: Dale E
authors.initials: DE
authors.lastname: Bockman
authors.forename: Junchao
authors.initials: J
authors.lastname: Guo
authors.forename: Michael W
authors.initials: MW
authors.lastname: Müller
authors.forename: Helmut
authors.initials: H
authors.lastname: Friess
authors.forename: Markus W
authors.initials: MW
authors.lastname: Büchler
mesh_terms: D000208:Acute Disease; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000473:pathology; D002463:Cell Membrane Permeability / Q000187:drug effects; D002108:Ceruletide / Q000008:administration & dosage / Q000633:toxicity; D003911:Dextrans / Q000493:pharmacokinetics; D005293:Ferritins / Q000737:chemistry / Q000493:pharmacokinetics; D005452:Fluoresceins / Q000493:pharmacokinetics; D005456:Fluorescent Dyes / Q000493:pharmacokinetics; D008297:Male; D008970:Molecular Weight; D010195:Pancreatitis / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D003911:Dextrans; D005452:Fluoresceins; D005456:Fluorescent Dyes; C052526:fluorescein-dextran; D002108:Ceruletide; D005293:Ferritins