INTERACTION BETWEEN APO-B AND HEPATIC LIPASE MEDIATES THE UPTAKE OF APO-B-CONTAINING LIPOPROTEINS

Hepatic lipase (HL) on the surface of hepatocytes and endothelial cell s lining hepatic sinusoids, the adrenal glands, and the ovary hydrolyz es triglycerides and phospholipids of circulating Lipoproteins. Its ex pression significantly enhances low density lipoprotein (LDL) uptake v ia the LDL receptor pathway. A specific interaction between LPL, a hom ologous molecule to HL, and apoB has been described (Choi, S. Y,, Siva ram, P,, Walker, D. E,, Curtiss, L, I,, Gretch, D, G,, Sturley, S. L,, Attie, A. D,, Deckelbaum, Il, J,, and Goldberg, I. J, (1995) J. Biol. Chem. 270, 8081-8086), The present studies tested the hypothesis that HL enhances the uptake of lipoproteins by a specific interaction of H L with apoB, On a ligand blot, HL bound to apoB26, 48, and 100 but not to apoE or apoAI, HL binding to LDL in a plate assay with LDL-coated plates was significantly greater than to bovine serum albumin-coated p lates. Neither heat denatured HL nor bacterial fusion protein of HL bo und to LDL in the plate assays. I-125-LDL bound to HL-saturated hepari n-agarose gel with a K-d of 52 nM, and somewhat surprisingly, this bin ding was not inhibited by excess LPL, In cell culture experiments HL e nhanced the uptake of I-125-LDL,at both 4 and 37 degrees C, The enhanc ed binding and uptake of LDL was significantly inhibited by monoclonal anti-apoB antibodies. In contrast to LPL, both amino- and carboxyl-te rminal antibodies blocked the apoB interaction with HL to the same ext ent. Thus, we conclude that there is a unique interaction between HL a nd apoB that facilitates the uptake of apoB-containing lipoproteins by cells where HL is present.