HDL 3-retroendocytosis in cultured small intestinal crypt cells: a novel mechanism of cholesterol efflux

Abstract

The present study in IEC-6 crypt-derived rat epithelial cells describes a retroendocytotic pathway for HDL 3. These intestinal cells exhibited specific binding of apoE free HDL 3 with a maximal binding capacity of 2980 ng/mg cell protein and a K d of 36.4 μg/ml. Specific binding was competed for by HDL 3 but not by LDL. Apparent internalisation of HDL 3 was low, degradation was negligible and intact particles were resecreted into the medium within 2 h. Electron microscopic studies showed binding and internalisation of gold-labeled HDL 3 in coated pit regions and transport in endosomes distinct from lysosomes to lipid droplets. De novo cholesterol synthesis from [ 14C]octanoate was enhanced nearly 2-fold by HDL 3 and the surplus of newly formed cholesterol was recovered in the medium. It was concluded that intact HDL 3 was bound specifically to intestinal cells and was resecreted through a process of retroendocytosis probably mediating efflux of cellular cholesterol.