Relative importance of the LDL receptor and scavenger receptor class B in the beta-VLDL-induced uptake and accumulation of cholesteryl esters by peritoneal macrophages

We investigated the mechanism of beta-very low density lipoprotein (beta-VL DL)-induced foam cell formation derived from peritoneal macrophages from co ntrol mice and low density lipoprotein (LDL) receptor-deficient mice to elu cidate the role of the LDL receptor in this process. The LDL receptor appea red to be of major importance for beta-VLDL metabolism. Consequently, the a ccumulation of cholesteryl esters in LDL receptor(-/-) macrophages is 2.5-f old lower than in LDL receptor(+/+) macrophages, In the absence of the LDL receptor, however, beta-VLDL was still able to induce cholesteryl ester acc umulation and subsequently we characterized the properties of this residual beta-VLDL recognition site(s) of LDL receptor(-/-) macrophages, Although t he LDL receptor-related protein is expressed on LDL receptor(-/-) macrophag es, the cell association of beta-VLDL is not influenced by the receptor-ass ociated protein, and treatment of the macrophages with heparinase and chond roitinase was also ineffective. In contrast, both oxidized LDL (OxLDL) and anionic liposomes were able to inhibit the cell association of I-125-labele d beta-VLDL in LDL receptor(-/-) macrophages by 65%. These properties sugge st a role for scavenger receptor class B (SR-B), and indeed, in the LDL rec eptor(-/-) macrophages the selective uptake of cholesteryl esters from beta -VLDL was 2.2-fold higher than that of apolipoproteins, a process that coul d be inhibited by OxLDL, high density lipoprotein (HDL), and beta-VLDL. In conclusion, the LDL receptor on peritoneal macrophages is directly involved in the metabolism of beta-VLDL and the subsequent foam cell formation. Whe n the LDL receptor is absent, SR-B appears to mediate the remaining metabol ism of cholesteryl esters from beta-VLDL.