In order to determine the contribution of the low density lipoprotein recep
tor (LDL-R) to the removal of apoB-containing native lipoproteins by macrop
hages, 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 lipopro
teins obtained from apoE deficient mice fed a high fat diet were poorly deg
raded by macrophages and caused only a slight formation of CE in macrophage
s from both types of mice. On the other hand, d < 1.006 g/ml lipoproteins o
btained 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 inhibi
ted 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 lip
oproteins by murine macrophages is primarily mediated by the LDL receptor a
nd not by other apoE-recognizing receptor systems such as: the LDL receptor
related protein, the VLDL receptor or the triglyceride-rich lipoprotein re
ceptor. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.