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 (L DL) with other modified forms of LDL in mouse peritoneal macrophages a nd PMA-activated human U937 monocytes. Neuraminidase-treated LDL (NT-L DL) caused significant cholesterol ester accumulation in both cell typ es, although the efficiency relative to loading with acetylated LDL (A cLDL) was markedly different, suggesting a very different complement o f receptors in the cells. We therefore determined the effect of PMA-ac tivation on lipoprotein receptor expression in U937 cells and found th at while scavenger receptor concentration was elevated after PMA-activ ation, there was no significant change in the expression of the LDL re ceptor. Receptor specificity of NT-LDL uptake was examined by competit ion experiments using the degradation assay. This showed that.I-125-la belled NT-LDL uptake in U937 cells could largely be accounted for by t he persistent expression of the LDL receptor in these cells. In contra st, in mouse peritoneal macrophages where LDL receptor expression is v ery low, I-125-labelled NT-LDL degradation was effectively competed by asialofetuin. Surprisingly, I-125-labelled NT-LDL degradation was als o effectively competed by AcLDL. Measurement of sialic acid content of AcLDL showed that approximately 14% of the LDL sialic acid, equivalen t to 2 to 3 residues per particle, was lost during acetylation of LDL with acetic anhydride. Thus competition between I-125-labelled NT-LDL and AcLDL could be due to lectin receptor binding rather than competit ion for scavenger receptor binding.