© 1998 American Heart Association, Inc.
Original Contributions |
Apolipoprotein B-48 or Its Apolipoprotein B-100 Equivalent Mediates the Binding of Triglyceride-Rich Lipoproteins to Their Unique Human Monocyte-Macrophage Receptor
From the University of Alabama at Birmingham, Department of Medicine, Division of Gerontology and Geriatrics (S.H.G., R.S., M.L.B., W.A.B.), Birmingham, Ala; and the Department of Medicine, University of California at San Diego (M.P.R.).
Correspondence to Sandra H. Gianturco, PhD, and William A. Bradley, PhD, 690 Diabetes Research and Education Building, University of Alabama at Birmingham, 1808 Seventh Ave S, Birmingham, AL 35294-0012.
Abstract—Studies in animals and humans have demonstrated uptake of plasma chylomicrons (triglyceride-rich lipoprotein [TGRLP] of Sf>400) by accessible macrophages in vivo. One potential mechanism is via a unique receptor pathway we previously identified in human blood and THP-1 monocytes and macrophages for the lipoprotein lipase (LpL)– and apolipoprotein (apo) E–independent, high-affinity, specific binding of plasma chylomicrons and hypertriglyceridemic VLDL (HTG-VLDL) to cell-surface membrane-binding proteins (MBP 200, 235; apparent Mr 200, 235 kD on SDS-PAGE) that leads to lipid accumulation in vitro. Competitive binding studies reported here demonstrate that anti-apoB antibodies specifically block the high-affinity binding of TGRLP to this receptor on THP-1 cells and on ligand blots. LpL, which binds to an N-terminal domain of apoB, also inhibits TGRLP binding both to this site on THP-1s and to MBP 200, 235 by binding to apoB. Chylomicrons of Sf>1100 that contain apoB-48, but not apoB-100, bind specifically to MBP 200, 235, and this binding is blocked by anti-apoB IgG. In contrast, lactoferrin and heparin do not inhibit TGRLP binding. We conclude that the receptor-binding domain is within apoB-48 (or an equivalent in apoB-100) near the LpL-binding domain, but not a heparin-binding domain. Uptake of TGRLP by this mechanism could provide essential nutrients or, in HTG, cause excess lipid accumulation and foam cell formation.
Key Words: foam cells • atherosclerosis • hypertriglyceridemia
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