The LDL receptor is the major pathway for β-VLDL uptake by mouse peritoneal macrophages

In order to determine the contribution of the low density lipoprotein receptor (LDL-R) to the removal of apoB-containing native lipoproteins by macrophages, we compared the uptake of beta -VLDL in peritoneal macrophages (MPM) from wild type mice and mice lacking the LDL-R. The d < 1.006 g/ml lipoproteins obtained from apoE deficient mice fed a high fat diet were poorly degraded by macrophages and caused only a slight formation of CE in macrophages from both types of mice. On the other hand, d < 1.006 g/ml lipoproteins obtained from LDL-R deficient mice fed a high fat diet, beta -VLDL with apoE, were avidly taken up by and markedly stimulated CE formation in wild type macrophages, but not in macrophages lacking the LDL-R. The degradation of I-125-labeled-apoE-containing beta -VLDL by wild type MPM was poorly inhibited by unlabeled human LDL, and beta -VLDL without apoE had no effects. In conclusion, we propose that the in vitro uptake of native apoE-enriched lipoproteins by murine macrophages is primarily mediated by the LDL receptor and not by other apoE-recognizing receptor systems such as: the LDL receptor related protein, the VLDL receptor or the triglyceride-rich lipoprotein receptor. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.