Apolipoprotein B-48 or its apolipoprotein B-100 equivalent mediates the binding of triglyceride-rich lipoproteins to their unique human monocyte-macrophage receptor.
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.
Gianturco
S H
SH
Department of Medicine, University of Alabama at Birmingham, 35294-0012, USA.
Ramprasad
M P
MP
Song
R
R
Li
R
R
Brown
M L
ML
Bradley
W A
WA
D000906:Antibodies / Q000378:metabolism; D053299:Apolipoprotein B-100; D053283:Apolipoprotein B-48; D001055:Apolipoproteins B / Q000378:metabolism*; D002914:Chylomicrons / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D006493:Heparin / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D007781:Lactoferrin / Q000378:metabolism / Q000494:pharmacology; D008071:Lipoprotein Lipase / Q000378:metabolism; D008079:Lipoproteins, VLDL / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism*; D011973:Receptors, LDL / Q000378:metabolism; D018110:Receptors, Lipoprotein / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000906:Antibodies; D053299:Apolipoprotein B-100; D053283:Apolipoprotein B-48; D001055:Apolipoproteins B; D002914:Chylomicrons; D008079:Lipoproteins, VLDL; D011973:Receptors, LDL; D018110:Receptors, Lipoprotein; D014280:Triglycerides; C028203:chylomicron receptor; C030106:very low density lipoprotein triglyceride; D006493:Heparin; D008071:Lipoprotein Lipase; D007781:Lactoferrin