Editorial
Copyright ©2006 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Apr 7, 2006; 12(13): 1985-1990
Published online Apr 7, 2006. doi: 10.3748/wjg.v12.i13.1985
Co-localization hypothesis: A mechanism for the intrapancreatic activation of digestive enzymes during the early phases of acute pancreatitis
Gijs JD van Acker, George Perides, Michael L Steer
Gijs JD van Acker, George Perides, Michael L Steer, Department of Surgery and the Boston Pancreas Group, Tufts-New England Medical Center, 860 Washington Street, Boston, MA 02111, United States
Author contributions: All authors contributed equally to the work
Correspondence to: Dr. Gijs Van Acker, Department of Surgery Tupper 2, Tufts-New England Medical Center, 860 Washington Street, Boston, MA 02111, United States. msteer@tufts-nemc.org
Telephone: +1-617-6369248 Fax: +1- 617-6369095
Received: October 31, 2005
Revised: December 5, 2005
Accepted: December 12, 2005
Published online: April 7, 2006
Abstract

Acute pancreatitis is generally believed to be a disease in which the pancreas is injured by digestive enzymes that it normally produces. Most of the potentially harmful digestive enzymes produced by pancreatic acinar cells are synthesized and secreted as inactive zymogens which are normally activated only upon entry into the duodenum but, during the early stages of acute pancreatitis, those zymogens become prematurely activated within the pancreas and, presumably, that activation occurs within pancreatic acinar cells. The mechanisms responsible for intracellular activation of digestive enzyme zymogens have not been elucidated with certainty but, according to one widely recognized theory (the “co-localization hypothesis"), digestive enzyme zymogens are activated by lysosomal hydrolases when the two types of enzymes become co-localized within the same intracellular compartment. This review focuses on the evidence supporting the validity of the co-localization hypothesis as an explanation for digestive enzyme activation during the early stages of pancreatitis. The findings, summarized in this review, support the conclusion that co-localization of lysosomal hydrolases with digestive enzyme zymogens plays a critical role in permitting the intracellular activation of digestive enzymes that leads to acinar cell injury and pancreatitis.

Keywords: Acute pancreatitis; Digestive enzymes; Pancreatic acinar cells