Ws. Davidson et al., EFFECTS OF ACCEPTOR PARTICLE-SIZE ON THE EFFLUX OF CELLULAR FREE-CHOLESTEROL, The Journal of biological chemistry, 270(29), 1995, pp. 17106-17113
Several subspecies of human high density lipoprotein (HDL) have been s
hown to exist, and particle size is one parameter that can be used to
distinguish them, Recently, a small HDL subspecies has been described
that may be a particularly efficient acceptor of peripheral cell unest
erified (free) cholesterol (FC), To address the effects of particle si
ze on the ability of HDL to remove FC from cells, homogeneous, well de
fined HDL particles were reconstituted (rHDL) that varied in particle
diameter within the size range of human HDL particles (7-13 nm), The a
bilities of each of these particles to remove cellular FC from mouse L
-cells and rat Fu5AH hepatoma cells were compared on the basis of thei
r phospholipid (PL) content as well as on a per particle basis, The ef
fect of particle size was also examined using small unilamellar vesicl
es (SUV) of 25 nm in diameter and large unilamellar vesicles (LUVs) of
70-180 nn in diameter, The SUV were prepared by sonication, and the L
UVs were prepared by extrusion techniques, The FC efflux efficiency of
these particles (in order of decreasing efficiency) was: rHDL > SUV >
LUV when compared on the basis of acceptor PL content across a range
of concentrations (i.e. at a given PL concentration for these three ac
ceptor classes, smaller particles were more efficient), The FC efflux
differences between the rHDL and the vesicles were not due to the abse
nce of apolipoprotein in the vesicles, No difference was detected amon
g the rHDL of varying size, nor was a difference detected among the LU
Vs of varying size when compared on the basis of PL content, When the
FC efflux data for rHDL and LUVs were normalized on the basis of the n
umber of acceptor particles present at a given PL concentration, a cor
relation was found between acceptor particle radius and the ability to
accept cellular FC with larger particles being the most efficient, Ho
wever, the dependence of the rate of FC efflux on acceptor particle si
ze was not quantitatively the same within the rHDL and LUV classes of
acceptor particles, The dependence of FC efflux on acceptor particle s
ize may reflect differing abilities of the variously sized acceptor pa
rticles to access the region very close to the cell plasma membrane wh
ere most of the FC removal is expected to occur.