The LDL receptor is the major pathway for beta-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 125I-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.
Perrey
S
S
Department of Metabolic Diseases, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, 113-8655, Tokyo, Japan.
Ishibashi
S
S
Kitamine
T
T
Osuga
J
J
Yagyu
H
H
Chen
Z
Z
Shionoiri
F
F
Iizuka
Y
Y
Yahagi
N
N
Tamura
Y
Y
Ohashi
K
K
Harada
K
K
Gotoda
T
T
Yamada
N
N
D000818:Animals; D001057:Apolipoproteins E / Q000032:analysis / Q000235:genetics; D002784:Cholesterol / Q000378:metabolism; D002788:Cholesterol Esters / Q000096:biosynthesis; D008074:Lipoproteins / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000494:pharmacology; D008079:Lipoproteins, VLDL / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism*
D001057:Apolipoproteins E; D002788:Cholesterol Esters; D008074:Lipoproteins; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D011973:Receptors, LDL; D002784:Cholesterol