Lysosome-Associated Membrane Protein-2: A Major Player in the Pathogenesis of Chronic Pancreatitis.

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The mechanisms involved in the development of either acute or chronic pancreatitis are not well understood, but previous reports have suggested that the pathogenesis of acute pancreatitis may involve a blockade of autophagic flux. 1 In the current issue ofCellular and Molecular Gastroenterology and Hepatology, Mareninova et al 2 from the Gukovskaya and Lerch groups have reported the results of studies investigating the role of lysosome-associated membrane protein-2 (LAMP-2) in the development of acute and chronic pancreatitis and in the regulation of successful autophagy in pancreatic acinar cells. In their report, they show that LAMP-1 and LAMP-2 levels are reduced in pancreas samples obtained from patients with acute pancreatitis, and they also note that similar changes occur during the evolution of five different animal models of acute pancreatitis. They find that this reduction in LAMP-2 levels occurs during the early phases of experimental pancreatitis and that it appears to be the result of LAMP-2 digestion by the lysosomal enzyme cathepsin B. The authors used LAMP-2–deficient mice in an attempt to evaluate whether there may be a cause and effect mechanism involved, and they found that the pancreatic acinar cells in LAMP-2 / mice contain reduced levels of amylase and trypsinogen as well as zymogen granules, suggesting that LAMP-2 is instrumental in maintaining pancreatic acinar cell homeostasis. The pancreatic acinar cells in LAMP-2 / mice exhibit