Desialylated LDL uptake in human and mouse macrophages can be mediated by a lectin receptor.
We have compared the uptake of desialylated low density lipoprotein (LDL) with other modified forms of LDL in mouse peritoneal macrophages and PMA-activated human U937 monocytes. Neuraminidase-treated LDL (NT-LDL) caused significant cholesterol ester accumulation in both cell types, although the efficiency relative to loading with acetylated LDL (AcLDL) was markedly different, suggesting a very different complement of receptors in the cells. We therefore determined the effect of PMA-activation on lipoprotein receptor expression in U937 cells and found that while scavenger receptor concentration was elevated after PMA-activation, there was no significant change in the expression of the LDL receptor. Receptor specificity of NT-LDL uptake was examined by competition experiments using the degradation assay. This showed that 125I-labelled NT-LDL uptake in U937 cells could largely be accounted for by the persistent expression of the LDL receptor in these cells. In contrast, in mouse peritoneal macrophages where LDL receptor expression is very low, 125I-labelled NT-LDL degradation was also effectively competed by asialofetuin. Surprisingly, 125I-labelled NT-LDL degradation was also effectively competed by AcLDL. Measurement of sialic acid content of AcLDL showed that approximately 14% of the LDL sialic acid, equivalent to 2 to 3 residues per particle, was lost during acetylation of LDL with acetic anhydride. Thus competition between 125I-labelled NT-LDL and AcLDL could be due to lectin receptor binding rather than competition for scavenger receptor binding.
Grewal
T
T
Heart Research Institute, NSW, Sydney, Australia.
Bartlett
A
A
Burgess
J W
JW
Packer
N H
NH
Stanley
K K
KK
D000818:Animals; D001212:Asialoglycoproteins / Q000378:metabolism; D001667:Binding, Competitive; D002788:Cholesterol Esters / Q000378:metabolism; D060748:Fetuins; D006801:Humans; D008077:Lipoproteins, LDL / Q000737:chemistry / Q000378:metabolism*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000473:pathology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism*; D008565:Membrane Proteins; D051379:Mice; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D019158:N-Acetylneuraminic Acid; D009439:Neuraminidase / Q000494:pharmacology; D011971:Receptors, Immunologic / Q000378:metabolism; D018110:Receptors, Lipoprotein; D011975:Receptors, Mitogen / Q000378:metabolism*; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B; D012794:Sialic Acids / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D000509:alpha-Fetoproteins / Q000378:metabolism
D001212:Asialoglycoproteins; D002788:Cholesterol Esters; D060748:Fetuins; D008077:Lipoproteins, LDL; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D011975:Receptors, Mitogen; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D012794:Sialic Acids; D000509:alpha-Fetoproteins; C017029:asialofetuin; D009439:Neuraminidase; D019158:N-Acetylneuraminic Acid; D013755:Tetradecanoylphorbol Acetate