Multiple processes are involved in the uptake of chylomicron remnants by mouse peritoneal macrophages

The processes responsible for the uptake of chylomicron remnants by macroph ages were investigated using freshly isolated cells from low density lipopr otein (LDL) receptor, very low density lipoprotein (VLDL) receptor and apol ipoprotein E knockout mice. In peritoneal macrophages from normal mice, the metabolism of chylomicron remnants was inhibited 40% by anti-LDL receptor antibody and 60% by a high concentration of receptor-associated protein (RA P), Together they reduced the amount processed by 70%. Digestion of cell pr oteoglycans decreased remnant degradation by 20% while the addition of acet yl-LDL had no effect. When LDL receptors were absent, the absolute rates of metabolism were less than that of normal cells and were not inhibited by t he anti-LDL receptor antibody; the rates, however, were reduced to less tha n half by RAP, These suggest that the LDL receptor-related protein (LRP) or another LDL receptor family member(s) contributes to chylomicron remnant u ptake and becomes the major mechanism of uptake when LDL receptors are abse nt. In contrast, the VLDL receptor was not involved as its absence did not affect chylomicron remnant metabolism, Similarly, the absence of apoE produ ction did not affect the amount of remnant uptake; however, the proportion that was sensitive to RAP was eliminated. The level of LRP expression was n ot altered in these cells whereas there was a decrease in LDL receptors, Th is suggests that the apoE content of chylomicron remnants is sufficient for its recognition by LDL receptors but additional apoE is required for its u ptake by the LRP and that there is an up-regulation of a non-LDL receptor f amily mechanism in apoE deficiency. Together these studies suggest that eve n in the absence of LDL receptors or apoE secretion, chylomicron remnants c ould contribute to lipid accumulation in the artery wall during atherogenes is.