title: Distinct murine macrophage receptor pathway for human triglyceride-rich lipoproteins.
abstract: Murine P388D1 macrophages have a receptor pathway that binds human hypertriglyceridemic very low density lipoproteins (HTG-VLDL) that is fundamentally distinct from the LDL receptor pathway. Trypsin-treated HTG-VLDL (tryp-VLDL), devoid of apolipoprotein (apo)-E, fail to bind to the LDL receptor, yet tryp-VLDL and HTG-VLDL cross-compete for binding to P388D1 macrophage receptors, indicating that these lipoproteins bind to the same sites. The specific, high affinity binding of tryp-VLDL and HTG-VLDL to macrophages at 4 degrees C is equivalent and at 37 degrees C both produce rapid, massive, curvilinear (receptor-mediated) triglyceride accumulation in macrophages. Ligand blots show that P388D1 macrophages express a membrane protein of approximately 190 kD (MBP190) that binds both tryp-VLDL and HTG-VLDL; this binding is competed by HTG-VLDL, trypsinized HTG-VLDL, and trypsinized normal VLDL but not by normal VLDL or LDL. The macrophage LDL receptor (approximately 130 kD) and cellular uptake of beta-VLDL, but not MBP 190 nor uptake of tryp-VLDL, are induced when cells are exposed to lipoprotein-deficient medium and decreased when cells are cholesterol loaded. Unlike the macrophage LDL receptor, MBP 190 partitions into the aqueous phase after phase separation of Triton X-114 extracts. An anti-LDL receptor polyclonal antibody blocks binding of HTG-VLDL to the LDL receptor and blocks receptor-mediated uptake of beta-VLDL by P388D1 cells but fails to inhibit specific cellular uptake of tryp-VLDL or to block binding of tryp-VLDL to MBP 190. Human monocytes, but not human fibroblasts, also express a binding protein for HTG-VLDL and tryp-VLDL similar to MBP 190. We conclude that macrophages possess receptors for abnormal human triglyceride-rich lipoproteins that are distinct from LDL receptors in ligand specificity, regulation, immunological characteristics, and cellular distribution. MBP 190 shares these properties and is a likely receptor candidate for the high affinity uptake of TG-rich lipoproteins by macrophages.
authors.affiliation: Department of Medicine, Baylor College of Medicine, Houston, Texas.
authors.forename: S H
authors.initials: SH
authors.lastname: Gianturco
authors.forename: A H
authors.initials: AH
authors.lastname: Lin
authors.forename: S L
authors.initials: SL
authors.lastname: Hwang
authors.forename: J
authors.initials: J
authors.lastname: Young
authors.forename: S A
authors.initials: SA
authors.lastname: Brown
authors.forename: D P
authors.initials: DP
authors.lastname: Via
authors.forename: W A
authors.initials: WA
authors.lastname: Bradley
mesh_terms: D000818:Animals; D001057:Apolipoproteins E; D001667:Binding, Competitive; D002352:Carrier Proteins / Q000378:metabolism*; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood*; D007941:Leukemia P388 / Q000378:metabolism; D008079:Lipoproteins, VLDL / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008970:Molecular Weight; D011973:Receptors, LDL / Q000032:analysis; D014357:Trypsin / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; D002352:Carrier Proteins; D008079:Lipoproteins, VLDL; D008565:Membrane Proteins; D011973:Receptors, LDL; D014357:Trypsin