Circulating bile salt-dependent lipase originates from the pancreas via intestinal transcytosis.
OBJECTIVE
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.
Bruneau
Nadine
N
INSERM U559, Unité de Recherche de Physiopathologie des Cellules Epithéliales and EA 3289, Université de la Mediterranée, Faculté de Médecine-Timone, Marseilles, France. Nadine.Bruneau@medecine.univ-mrs.fr
Bendayan
Moïse
M
Gingras
Diane
D
Ghitescu
Lucien
L
Levy
Emile
E
Lombardo
Dominique
D
D000042:Absorption; D000818:Animals; D002417:Cattle; D020895:Enterocytes / Q000378:metabolism*; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D008074:Lipoproteins / Q000378:metabolism; D008297:Male; D010179:Pancreas / Q000378:metabolism*; D010189:Pancreatic Juice / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D002787:Sterol Esterase / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics; D013997:Time Factors
D005456:Fluorescent Dyes; D008074:Lipoproteins; C054784:bile salt-stimulated lipase; D002787:Sterol Esterase; D016650:Fluorescein-5-isothiocyanate