Receptor activities for low-density lipoprotein and acetylated low-density lipoprotein in a mouse macrophage cell line (IC21) and in human monocyte-derived macrophages.

Abstract

IC21 macrophages, a permanent line derived from a single colony of mouse peritoneal macrophages transformed with SV40, demonstrate most of the characteristics of lipoprotein metabolism that have been described for primary cultures of rodent or canine peritoneal macrophages. IC21 macrophages have low but demonstrable low-density lipoprotein (LDL) receptor activity. They actively degrade acetylated LDL (AcLDL), which has a negative charge and is not recognized by the LDL receptor. Incubation of IC21 macrophages with human lipoprotein-depleted serum leads to a marked increase in cholesterol synthesis as measured by incorporation of labeled acetate into sterols. Sterol synthesis is inhibited by further incubation with AcLDL; incubation with LDL also decreases cholesterol synthesis with an accumulation of radioactivity from acetate in sterol intermediates, which indicates that some uptake of LDL occurs. Incubation with AcLDL but not LDL leads to a marked stimulation of cholesterol esterification, as measured by labeled oleic acid incorporation into cholesteryl esters, and a concomitant incrase in cellular cholesteryl ester content. IC21 macrophages, compared with human monocyte-derived (HMD) macrophages, have marked differences in their abilities to degrade native LDL and AcLDL. HMD macrophages degrade LDL at low concentrations at a rate 7-fold greater than do IC21 macrophages. The rate of cholesteryl ester synthesis after LDL receptor induction and incubation with LDL increases linearly with LDL concentration in HMD macrophages, but no increase was found in similarly incubated IC21 macrophages. IC21 macrophages degrade AcLDL at a rate 2- to 4-fold greater than do HMD macrophages.