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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2000;20:1074.)
© 2000 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Apolipoprotein AII Enrichment of HDL Enhances Their Affinity for Class B Type I Scavenger Receptor but Inhibits Specific Cholesteryl Ester Uptake

Antoine Pilon; Olivier Briand; Sophie Lestavel; Corinne Copin; Zouher Majd; Jean-Charles Fruchart; Graciela Castro; Véronique Clavey

From INSERM U325, Institut Pasteur de Lille et Université Lille 2, Lille, France.

Correspondence to V. Clavey, INSERM U325, Institut Pasteur de Lille, 1 rue du Professeur Calmette, BP 245, F-59019 Lille Cédex, France. E-mail Veronique.Clavey{at}pasteur-lille.fr

Abstract—Apolipoproteins of high density lipoprotein (HDL) and especially apolipoprotein (apo)AI and apoAII have been demonstrated as binding directly to the class B type I scavenger receptor (SR-BI), the HDL receptor that mediates selective cholesteryl ester uptake. However, the functional relevance of the binding capacity of each apolipoprotein is still unknown. The human adrenal cell line, NCI-H295R, spontaneously expresses a high level of SR-BI, the major apoAI binding protein in these cells. As previously described for murine SR-BI, free apoAI, palmitoyl-oleoyl-phosphatidylcholine (POPC)-AI, and HDL are good ligands for human SR-BI. In vitro displacement of apoAI by apoAII in HDLs or in Lp AI purified from HDL by immunoaffinity enhances their ability to compete with POPC-AI to bind to SR-BI and also enhances their direct binding capacity. The next step was to determine whether the higher affinity of apoAII for SR-BI correlated with the specific uptake of cholesteryl esters from these HDLs. Free apoAII and, to a lesser extent, free apoAI that were added to the cell medium during uptake experiments inhibited the specific uptake of [³H]cholesteryl esters from HDL, indicating that binding sites on cells were the same as cholesteryl ester uptake sites. In direct experiments, the uptake of [³H]cholesteryl esters from apoAII-enriched HDL was highly reduced compared with the uptake from native HDL. These results demonstrate that in the human adrenal cell line expressing SR-BI as the major HDL binding protein, efficient apoAII binding has an inhibitory effect on the delivery of cholesteryl esters to cells.

Key Words: adrenal cells • scavenger receptor, class B type I • cholesteryl esters • apolipoprotein AI • apolipoprotein AII

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