HDL3-retroendocytosis in cultured small intestinal crypt cells: a novel mechanism of cholesterol efflux.

The present study in IEC-6 crypt-derived rat epithelial cells describes a retroendocytotic pathway for HDL3. These intestinal cells exhibited specific binding of apoE free HDL3 with a maximal binding capacity of 2980 ng/mg cell protein and a Kd of 36.4 micrograms/ml. Specific binding was competed for by HDL3 but not by LDL. Apparent internalisation of HDL3 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 HDL3 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 HDL3 and the surplus of newly formed cholesterol was recovered in the medium. It was concluded that intact HDL3 was bound specifically to intestinal cells and was resecreted through a process of retroendocytosis probably mediating efflux of cellular cholesterol.