High-density lipoprotein 3 retroendocytosis: a new lipoprotein pathway in the enterocyte (Caco-2).

The present study in Caco-2 cells, derived from a human colon carcinoma and capable of enterocyte differentiation in culture, describes a retroendocytotic pathway for high-density lipoprotein 3 (HDL3). These cells exhibit specific binding of apolipoprotein E-free HDL3 which was competed for by HDL3 but not by low-density lipoproteins. At 37 degrees C, degradation was negligible and intact particles were internalized and resecreted into the medium within 2 hours. Electron microscopy showed binding and internalization of gold-labeled HDL3 in coated pit regions and transport in endosomes distinct from lysosomes to lipid droplets. The fusion of these endosomes with lipid droplets was followed by their dissolution and the subsequent extrusion of HDL particles from the cells. Fluorescence labeling studies of HDL3 supported cytosolic transport in vesicles. Specific binding showed negative feedback regulation by HDL3, was modulated by alterations in cellular cholesterol content, and increased with the cellular state of differentiation. HDL3 mediated efflux of endogenously labeled cholesterol. It is concluded that intact HDL3 is bound specifically by Caco-2 cells, leading to a subsequent intracellular passage and resecretion through a process of retroendocytosis effecting the efflux of cellular cholesterol.