The heparin-bound fraction of human lipoprotein-deficient serum inhibits endocytic uptake of oxidized low density lipoprotein by macrophages.
We recently demonstrated that bovine lactoferrin, a cationic whey protein from bovine milk, interacts with the negative charges of modified low density lipoproteins (modified LDL) such as acetylated LDL (acLDL) and oxidized LDL (oxLDL), which markedly interferes with their endocytic uptake by rat peritoneal macrophages (Kajikawa M, Ohta T, Takase M, Kawase K, Shimamura S, Matsuda I. Biochim Biophys Acta 1994;1213:82-90). In the present study, we examined whether human lipoprotein-deficient serum (LPDS) might contain protein(s) that could inhibit the endocytic uptake of oxLDL by mouse macrophages. We fractionated LPDS by heparin affinity chromatography and found that the cellular binding of oxLDL to mouse macrophages and subsequent endocytic uptake were inhibited by 50%-60% with the heparin-bound fraction, whereas the heparin-unbound fraction had no effect. Similar results were obtained in the experiments with acetylated LDL. Sephacryl S-300 gel-filtration chromatography of a mixture of oxLDL and the heparin-bound fraction revealed that a 150-kDa protein was associated with oxLDL. These results indicate that the electrostatic interaction of oxLDL with some component(s) of the heparin-bound fraction might interfere with the endocytic uptake of oxLDL by the macrophage scavenger receptor.
Suginohara
Y
Y
Department of Biochemistry, Kumamoto University School of Medicine, Japan.
Miyazaki
A
A
Hakamata
H
H
Sakamoto
Y
Y
Ohta
T
T
Matsuda
I
I
Horiuchi
S
S
D000818:Animals; D001798:Blood Proteins / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D002417:Cattle; D002846:Chromatography, Affinity; D003470:Culture Media / Q000737:chemistry; D004587:Electrophoresis, Agar Gel; D004705:Endocytosis / Q000187:drug effects*; D006493:Heparin / Q000378:metabolism*; D006801:Humans; D007781:Lactoferrin / Q000737:chemistry; D008074:Lipoproteins / Q000097:blood; D008077:Lipoproteins, LDL / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008817:Mice, Mutant Strains; D010084:Oxidation-Reduction; D011485:Protein Binding; D011971:Receptors, Immunologic / Q000378:metabolism; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B
D001798:Blood Proteins; D003470:Culture Media; D008074:Lipoproteins; D008077:Lipoproteins, LDL; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D006493:Heparin; D007781:Lactoferrin