Two independent lipoprotein receptors on hepatic membranes of dog, swine, and man. Apo-B,E and apo-E receptors.

We have reported previously that canine livers possess two distinct lipoprotein receptors, an apoprotein (apo)-B,E receptor capable of binding the apo-B-containing low density lipoproteins (LDL) and the apo-E-containing cholesterol-induced high density lipoproteins (HDLc), and an apo-E receptor capable of binding apo-E HDLc but not LDL. Both the apo-B,E and apo-E receptors were found on the liver membranes obtained from immature growing dogs, but only the apo-E receptors were detected on th hepatic membranes of adult dogs. In this study, the expression of the apo-B,E receptors, as determined by canine LDL binding to the hepatic membranes, was found to be highly dependent on the age of the dog and decreased linearly with increasing age. Approximately 30 ng of LDL protein per milligram of membrane protein were bound via the apo-B,E receptors to the hepatic membranes of 7- to 8-wk-old immature dogs as compared with no detectable LDL binding in the hepatic membranes of adult dogs (greater than 1--1.5 yr of age). Results obtained by in vivo turnover studies of canine 125I-LDL correlated with the in vitro findings. In addition to a decrease in the expression of the hepatic apo-B,E receptors with age, these receptors were regulated, i.e., cholesterol feeding suppressed these receptors in immature dogs and prolonged fasting induced their expression in adult dogs. Previously, it was shown that the apo-B,E receptors were induced in adult livers following treatment with the hypocholesterolemic drug cholestyramine. In striking contrast, the apo-E receptors, as determined by apo-E HDLc binding, remained relatively constant for all ages of dogs studied (10--12 ng/mg). Moreover, the expression of the apo-E receptors was not strictly regulated by the metabolic perturbations that regulated the apo-B,E receptors. Similar results concerning the presence of apo-B,E and apo-E receptors were obtained in swine and in man. The hepatic membranes of adult swine bound only apo-E HDLc (apo-E receptors), whereas the membranes from fetal swine livers bound both LDL and apo-E HDLc (apo B,E and apo-E receptors). Furthermore, the membranes from adult human liver revealed the presence of the apo-E receptors as evidenced by the binding of 12--14 ng of HDLc protein per milligram of membrane protein and less than 1 ng of LDL protein per milligram. The membranes from the human liver also bound human chylomicron remnants and a subfraction of human HDL containing apo-E. These data suggest the importance of the E apoprotein and the apo-E receptors in mediating lipoprotein clearance, including chylomicron remnants, by the liver of adult dogs, swine, and man.