Renal handling of plasma high density lipoprotein

Renal tubular reabsorption and hydrolysis of plasma high density lipoprotein (HDL3) were studied. Rabbit proximal straight nephron segments were microperfused in vitro with iodinated HDL3. Progressive luminal uptake and cellular accumulation of radiolabeled material were observed during an initial phase, followed by a reduction in sequestration and the appearance of 125I-label in the bathing medium. To detect proteolysis, collected perfusates and bathing media were analyzed for trichloracetic acid soluble radioactivity. 125I-HDL3 in the luminal fluid was intact, but metabolites appeared in the bathing medium. Electron microscopic radioautography demonstrated endocytic uptake of 125I-HDL3 at the luminal membrane of the proximal tubule and movement of grains into lysosome-like dense bodies. Incubation of radiolabeled HDL3 in the presence of renal homogenates resulted in proteolytic activity with an acidic pH optimum. Analytical cell fractionation studies indicated that hydrolysis of the protein component is associated with lysosomes derived from proximal kidney tubules. Collectively, the data show that plasma HDL3 can be reabsorbed in the proximal nephron by a mechanism involving endocytosis at the luminal membrane, followed by proteolysis at lysosomes.