LOCALIZATION OF AN APOLIPOPROTEIN-A-I EPITOPE CRITICAL FOR LIPOPROTEIN-MEDIATED CHOLESTEROL EFFLUX FROM MONOCYTIC CELLS

The inverse correlation between plasma high density lipoprotein (HDL) levels and the risk for cardiovascular disease has been attributed in part to the role of HDL in facilitating the transport of cholesterol t o the liver for catabolism. One component of this reverse cholesterol transport is removal of excess cholesterol from peripheral cells. An i mmunochemical approach was employed to evaluate the role of human apol ipoprotein (apo) A-I in cellular cholesterol efflux and to test the hy pothesis that discrete structural domains of the molecule mediate this function. Two apoA-I-specific monoclonal antibodies (AI-11 and AI-14) inhibited in vitro cellular cholesterol efflux from THP-1 monocytic c ells to HDL or apoA-I proteoliposomes by approximately 50%. Six other antibodies had no effect although three of these bound significant pro portions of the apoA-I proteoliposomes. Antibody AI-11 binds apoA-I am ino acid residues 96-111 (Banka, C. L., Bonnet, D. J., Black, A. S., S mith, R. S., and Curtiss, L. K, (1991) J. Biol. Chem. 266, 23886-23892 ). The AI-14 epitope was localized to residues 74-105. Therefore, the two antibodies that inhibited HDL promotion of cellular cholesterol ef flux bound overlapping but distinct regions of the apoA-I molecule.