Interaction of Tangier lipoproteins with cholesteryl ester-laden mouse peritoneal macrophages

Abstract

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.