Journal of Lipid Research, Vol 31, 2133-2139, Copyright © 1990 by Lipid Research, Inc.
ApoE-3-specific metabolism of human plasma very low density lipoproteins in cultured J-774 macrophages
E Granot and S Eisenberg
Department of Pediatrics, Hadassah University Hospital, Jerusalem, Israel.
The effect of apoprotein E on the cellular metabolism of very low density
lipoproteins (VLDL) was studied using the J-774 macrophage-like cell line
as a foam cell model. Exogenous (plasmatic and recombinant) apoE-3 caused a
marked enhancement of the cellular binding, association, and degradation of
VLDL fractions I, II, and III from both normolipidemic and
hypertriglyceridemic subjects. ApoE-3 did not affect the cellular
metabolism of low density lipoproteins (LDL). The stimulatory effect of
apoE-3 was specific and was not observed with E- 2. ApoE-mediated
enhancement of VLDL metabolism was markedly suppressed by competition with
LDL or by down-regulation of the LDL receptor while the basal cellular
metabolism of VLDL was not. The macrophage, however, appears also to
exhibit a second apoE-3-dependent pathway for VLDL metabolism which is
discerned from the LDL and scavenger receptors and is relatively resistant
to cholesterol in the culture medium. This pathway is responsible for the
basal and perhaps a small fraction of the apoE-3-stimulated metabolism of
VLDL in the macrophage. Such activity may play a role in promoting foam
cell formation by triglyceride-rich lipoproteins.