Abstract

High density lipoprotein (HDL) is known to participate in the removal of free cholesterol from cholesterol-loaded cultured macrophages. To provide some morphological evidence to this phenomenon, endocytic uptake and intracellular pathway of HDL in rat petironeal macrophages were investigated at the electron microscopic level. A horseradish peroxidase conjugate of HDL (HDL-HRP) showed specific binding to coated pits of the plasma membrane on the incubation with the cells at 4°C. When the cells were warmed to 37°C for various periods, HDL-HRP was internalized and delivered through coated vesicles and tubulo-vesicular system to endosomes at the periphery of cytoplasm. Further incubation revealed the distribution in endosomes of the Golgi region as well as trans-Golgi vesiceles, followed by resecretion out of the cells. Thus, these results disclosed the unique endocytosis -resecretion pathway of HDL in macrophages that we call HDL pathway. In addition, comparing the intracellular pathway of transferrin by the same approach, transferrin-HRP conjugates showed their indistinguishable movement through trans-Golgi vesicles from that of HDL.Trans-Golgi system has recently been emphasized to play an important role in receptor recycling as well as membrane sorting (Pastan & Willingham). In the light of the present findings, we believe that HDL shares the same fate as transferrin through this compartment. Furthermore, it could be postulated that cholesterol transport from cholesterolloaded macrophages to HDL molecule might occur in this unique HDL pathway.

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