In this study, we compared cholesterol efflux mediated by either high
density lipoproteins (HDL(3)) or beta-cyclodextrins, cyclic oligosacch
arides that are able to dis solve lipids in their hydrophobic core. be
ta-Cyclodextrin, 2-hydroxypropyl-beta-cyclodextrin, and methyl-beta-cy
clodextrin at 10 mM induced the release of 50-90% of L-cell [H-3]chole
sterol after 8 h of incubation, with a major portion of this cholester
ol being released in the first 1-2 h of incubation. The cholesterol ef
flux kinetics are different if cells are incubated with HDL(3), which
induces a relatively constant rate of release of cholesterol throughou
t an 8-h incubation. Cholesterol efflux to cyclodextrins was much grea
ter than phospholipid release. To test the hypothesis that maximal eff
lux rate constants for a particular cell are independent of the type o
f acceptor, we estimated the maximal rate constants for efflux (V-max)
of cellular cholesterol from L-cells, Fu5AH cells, and GM3468A fibrob
lasts. The rate constant for HDL(3)-mediated efflux varied among cell
lines in the order Fu5AH > L-cells > fibroblasts. However, these diffe
rences were not evident when cyclodextrins were used as cholesterol ac
cepters. The estimated V-max values for cyclodextrin-mediated efflux w
ere 3.5-70-fold greater than for HDL(3) for the three cell lines. The
very high efficiency of cyclodextrins in stimulating cell cholesterol
efflux suggests that these compounds can be used in two general ways f
or studies of atherosclerosis: 1) as research tools to probe mechanism
s of cholesterol transport and aspects of membrane structure or 2) as
potential pharmacological agents that could modify in vivo cholesterol
metabolism and influence the development of the atherosclerotic plaqu
e.