Role of scavenger receptors SR-BI and CD36 in selective sterol uptake in the small intestine

The serum lipoprotein high-density lipoprotein (HDL), which is a ligand of scavenger receptors such as scavenger receptor class B type I (SR-BI) and c luster determinant 36 (CD36), can act as a donor particle for intestinal li pid uptake into the brush border membrane (BBM). Both cholesterol and phosp holipids are taken up by the plasma membrane of BBM vesicles (BBMV) and Cac o-2 cells in a facilitated (protein-mediated) process. The protein-mediated transfer of cholesterol from reconstituted HDL to BBMV depends on the lipi d composition of the HDL. In the presence of sphingomyelin, the transfer of cholesterol is slowed by a factor of about 3 probably due to complex forma tion between cholesterol and the sphingolipid. It is shown that the mechani sm of lipid transfer from reconstituted HDL to either BBMV or Caco-2 cells as the acceptor is consistent with selective lipid uptake: the lipid donor docks at the membrane-resident scavenger receptors which mediate the transf er of lipids between donor and acceptor. Selective lipid uptake implies tha t lipid, but no apoprotein is transferred from the donor to the BBM, thus e xcluding endocytotic processes. The two BBM models used here clearly indica te that fusion of donor particles with the BBM can be ruled out as a major mechanism contributing to intestinal lipid uptake. Here we demonstrate that CD36, another member of the family of scavenger receptors, is present in r abbit and human BBM vesicles. This receptor mediates the uptake of free cho lesterol, but not of esterified cholesterol, the uptake of which is mediate d exclusively by SR-BI. More than one scavenger receptor appears to be invo lved in the uptake of free cholesterol with SR-BI contributing about 25% an d CD36 about 35%. There is another yet unidentified protein accounting for the remaining 30 to 40%.