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

Nicole Herijgers, Miranda Van Eck, Suzanne J.A. Korporaal, Peter M. Hoogerbrugge, Theo J.C. Van Berkel

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

19 Citaten (Scopus)

Samenvatting

We investigated the mechanism of β-very low density lipoprotein (β- VLDL)-induced foam cell formation derived from peritoneal macrophages from control mice and low density lipoprotein (LDL) receptor-deficient mice to elucidate the role of the LDL receptor in this process. The LDL receptor appeared to be of major importance for β-VLDL metabolism. Consequently, the accumulation of cholesteryl esters in LDL receptor(-/-) macrophages is 2.5- fold lower than in LDL receptor(+/+) macrophages. In the absence of the LDL receptor, however, β-VLDL was still able to induce cholesteryl ester accumulation and subsequently we characterized the properties of this residual β-VLDL recognition site(s) of LDL receptor(-/-) macrophages. Although the LDL receptor-related protein is expressed on LDL receptor(-/-) macrophages, the cell association of β-VLDL is not influenced by the receptor-associated protein, and treatment of the macrophages with heparinase and chondroitinase was also ineffective. In contrast, both oxidized LDL (OxLDL) and anionic liposomes were able to inhibit the cell association of 125I-labeled β-VLDL in LDL receptor(-/-) macrophages by 65%. These properties suggest a role for scavenger receptor class B (SR-B), and indeed, in the LDL receptor(-/-) macrophages the selective uptake of cholesteryl esters from β-VLDL was 2.2-fold higher than that of apolipoproreins, a process that could be inhibited by OxLDL, high density lipoprotein (HDL), and β-VLDL. In conclusion, the LDL receptor on peritoneal macrophages is directly involved in the metabolism of β-VLDL and the subsequent foam cell formation. When the LDL receptor is absent, SR-B appears to mediate the remaining metabolism of cholesteryl esters from β-VLDL.

Originele taal-2Engels
Pagina's (van-tot)1163-1171
Aantal pagina's9
TijdschriftJournal of Lipid Research
Volume41
Nummer van het tijdschrift7
StatusGepubliceerd - jul. 2000
Extern gepubliceerdJa

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