Bruneau Nadine, Bendayan Moïse, Gingras Diane, Ghitescu Lucien, Levy Emile, Lombardo Dominique
INSERM U559, Unité de Recherche de Physiopathologie des Cellules Epithéliales and EA 3289, Université de la Mediterranée, Faculté de Médecine-Timone, Marseilles, France.
Gastroenterology. 2003 Feb;124(2):470-80. doi: 10.1053/gast.2003.50051.
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.
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.
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.
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.
在人体血液中已检测到胆汁盐依赖性脂肪酶(BSDL),据推测它在动脉粥样硬化中起重要作用。这种循环酶的来源尚不清楚。本研究的目的是表明血液中的BSDL通过跨肠道上皮的转胞吞作用源自胰腺外分泌。
将异硫氰酸荧光素或[(125)I]标记的人胰腺BSDL注入大鼠肠袢腔内,并对这些动物的肠细胞和血液进行生化与免疫细胞化学联合研究。
体内胰腺BSDL被十二指肠肠上皮细胞内化。胰腺酶与微绒毛相关,存在于内吞小泡和高尔基体以及肠上皮细胞的基底外侧膜上。在肠间隙中也检测到了它。十二指肠上皮内化的放射性标记胰腺BSDL是在循环中进一步检测到的那种。放射性标记蛋白从血浆中免疫沉淀出来,其分子量为100千道尔顿,与天然胰腺BSDL相符。在血液中,BSDL主要与低密度脂蛋白相关。
这些体内数据表明,正常存在于血液中的BSDL源自胰腺外分泌,并支持BSDL通过肠黏膜细胞内衬进行转胞吞作用的病理生理学相关性。基于此,循环BSDL在动脉粥样硬化中的作用值得密切关注。