BACKGROUND & AIMS: Bile salt-dependent lipase (BSDL) has been detected in human blood, where it is assumed to play a substantial role in atherosclerosis. The origin of this circulating enzyme is unknown. The aim of this study was to show that blood BSDL originates from pancreatic exocrine secretions via a transcytotic motion across the intestinal epithelium. METHODS: Fluorescein isothiocyanate- or [(125)I]-labeled human pancreatic BSDL was instilled into the lumen of intestinal loops of the rat, and combined biochemical and immunocytochemical investigations were performed in intestinal cells and in the blood of these animals. RESULTS: In vivo pancreatic BSDL is internalized by duodenal enterocytes. The pancreatic enzyme was associated with microvilli and present in endocytic vesicles and Golgi apparatus as well as along the basolateral membrane of enterocytes. It was also detected in intestinal interstitial spaces. Radiolabeled pancreatic BSDL internalized by the duodenal epithelium is the one further detected in circulation. The radiolabeled protein was immunoprecipitated from plasma and had a 100-kilodalton molecular mass compatible with native pancreatic BSDL. In blood, BSDL was mainly associated with low-density lipoproteins. CONCLUSIONS: These in vivo data show that BSDL, normally present in blood, originates from exocrine pancreatic secretion and support the pathophysiologic relevance of BSDL transcytosis through the intestinal mucosa cell lining. Based on this, the implication of circulating BSDL in atherosclerosis merits careful attention.
BACKGROUND & AIMS:Bile salt-dependent lipase (BSDL) has been detected in human blood, where it is assumed to play a substantial role in atherosclerosis. The origin of this circulating enzyme is unknown. The aim of this study was to show that blood BSDL originates from pancreatic exocrine secretions via a transcytotic motion across the intestinal epithelium. METHODS:Fluorescein isothiocyanate- or [(125)I]-labeled humanpancreatic BSDL was instilled into the lumen of intestinal loops of the rat, and combined biochemical and immunocytochemical investigations were performed in intestinal cells and in the blood of these animals. RESULTS: In vivo pancreatic BSDL is internalized by duodenal enterocytes. The pancreatic enzyme was associated with microvilli and present in endocytic vesicles and Golgi apparatus as well as along the basolateral membrane of enterocytes. It was also detected in intestinal interstitial spaces. Radiolabeled pancreatic BSDL internalized by the duodenal epithelium is the one further detected in circulation. The radiolabeled protein was immunoprecipitated from plasma and had a 100-kilodalton molecular mass compatible with native pancreatic BSDL. In blood, BSDL was mainly associated with low-density lipoproteins. CONCLUSIONS: These in vivo data show that BSDL, normally present in blood, originates from exocrine pancreatic secretion and support the pathophysiologic relevance of BSDL transcytosis through the intestinal mucosa cell lining. Based on this, the implication of circulating BSDL in atherosclerosis merits careful attention.
Authors: Marloes A Naarding; Annette M Dirac; Irene S Ludwig; Dave Speijer; Susanne Lindquist; Eva-Lotta Vestman; Martijn J Stax; Teunis B H Geijtenbeek; Georgios Pollakis; Olle Hernell; William A Paxton Journal: Antimicrob Agents Chemother Date: 2006-10 Impact factor: 5.191
Authors: Justin J Heynekamp; Lucy A Hunsaker; Thomas A Vander Jagt; Robert E Royer; Lorraine M Deck; David L Vander Jagt Journal: Bioorg Med Chem Date: 2008-03-06 Impact factor: 3.641
Authors: Janniche Torsvik; Stefan Johansson; Anders Johansen; Jakob Ek; Jayne Minton; Helge Raeder; Sian Ellard; Andrew Hattersley; Oluf Pedersen; Torben Hansen; Anders Molven; Pål R Njølstad Journal: Hum Genet Date: 2009-09-17 Impact factor: 4.132