Journal of Lipid Research, Vol 28, 87-99, Copyright © 1987 by Lipid Research, Inc.
Interaction of Tangier lipoproteins with cholesteryl ester-laden mouse peritoneal macrophages
G Schmitz, G Assmann, B Brennhausen and HJ Schaefer
Cholesterol efflux was studied from cholesteryl esterladen mouse peritoneal
macrophages in the presence of Tangier lipoproteins derived from fasting
and postprandial sera of three patients homozygous for Tangier disease
(analphalipoproteinemia). The d greater than 1.063 g/ml fractions isolated
from fasting patients and 3 hr and 18 hr after an oral fat load were all
effective in cellular cholesterol removal. By contrast, the d greater than
1.063 g/ml fractions isolated 6 hr and 12 hr after fat ingestion did not
affect net removal of cellular cholesterol. The d greater than 1.21 g/ml
protein fractions derived from fasting as well as postprandial sera were
all effective in removing cholesterol. D 1.063-1.21 g/ml fractions from
fasting Tangier patients contained HDLT. In the corresponding postprandial
fractions, in addition to HDLT, apoB-100- and apoB-48-containing
lipoproteins were present. Furthermore, the 6 hr and 12 hr postprandial
Tangier HDL fractions contained apoB-immunoreactive proteins of lower
molecular weight. The abnormal activity of the elastase/alpha 1-antitrypsin
proteolytic system and the abnormal fibronectin concentration we found in
Tangier plasma suggests a possible relationship to the in vivo degradation
of apoB. The peculiar type of membrane-bound lipid droplets in Tangier
splenic macrophages points to a lipoprotein source of lipid accumulation
which possibly originates from the uptake of chylomicrons or
chylomicron-derived particles. It is concluded that cholesteryl ester
storage in Tangier macrophages results from an imbalance of cholesterol
influx and efflux. In the absence of HDL, the net increase of cholesterol
caused by abnormal lipoproteins in certain postprandial states cannot be
fully compensated by effective efflux and ultimately leads to macrophage
cholesteryl ester accumulation.