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

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

Nicole Herijgers^a, Miranda Van Eck^a, Suzanne J. A. Korporaal^a, Peter M. Hoogerbrugge^b, and Theo J. C. Van Berkel^a
^a Division of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research, Sylvius Laboratories, Leiden University, 2333 AL Leiden, The Netherlands
^b Department of Pediatrics, University Hospital, 6525 GA Nijmegen, The Netherlands

Correspondence to: Theo J. C. Van Berkel

We investigated the mechanism of ß-very low density lipoprotein(ß-VLDL)-induced foam cell formation derived from peritonealmacrophages from control mice and low density lipoprotein (LDL)receptor-deficient mice to elucidate the role of the LDL receptorin this process. The LDL receptor appeared to be of major importancefor ß-VLDL metabolism. Consequently, the accumulationof cholesteryl esters in LDL receptor^-^/- macrophages is 2.5-foldlower than in LDL receptor⁺^/⁺ macrophages. In the absence ofthe LDL receptor, however, ß-VLDL was still able to inducecholesteryl ester accumulation and subsequently we characterizedthe properties of this residual ß-VLDL recognition site(s)of LDL receptor^-^/- macrophages. Although the LDL receptor-relatedprotein is expressed on LDL receptor^-^/- macrophages, the cellassociation of ß-VLDL is not influenced by the receptor-associatedprotein, and treatment of the macrophages with heparinase andchondroitinase was also ineffective. In contrast, both oxidizedLDL (OxLDL) and anionic liposomes were able to inhibit the cellassociation of ¹²⁵I-labeled ß-VLDL in LDL receptor^-^/-macrophages by 65%. These properties suggest a role for scavengerreceptor class B (SR-B), and indeed, in the LDL receptor^-^/-macrophages the selective uptake of cholesteryl esters fromß-VLDL was 2.2-fold higher than that of apolipoproteins,a process that could be inhibited by OxLDL, high density lipoprotein(HDL), and ß-VLDL.

In conclusion, the LDL receptor on peritoneal macrophages isdirectly involved in the metabolism of ß-VLDL and thesubsequent foam cell formation. When the LDL receptor is absent,SR-B appears to mediate the remaining metabolism of cholesterylesters from ß-VLDL.—Herijgers, N., M. Van Eck, S.J. A. Korporaal, P. M. Hoogerbrugge, and T. J .C. Van Berkel.Relative importance of the LDL receptor and scavenger receptorclass B in the ß-VLDL-induced uptake and accumulationof cholesteryl esters by peritoneal macrophages. J. Lipid Res.2000. 41: 1163–1171.

Supplementary key words: atherosclerosis

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Original Article

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