SCAVENGER RECEPTOR CLASS-B TYPE-I AS A MEDIATOR OF CELLULAR CHOLESTEROL EFFLUX TO LIPOPROTEINS AND PHOSPHOLIPID ACCEPTORS

We recently reported that the rate of efflux of cholesterol from cells to high density lipoprotein (HDL) was related to the expression level of scavenger receptor class B type I (SR-BI). Moreover, the expressio n of this receptor in atheromatous arteries raises the possibility tha t SR-BI mediates cholesterol efflux in the arterial wall (Ji, Y., Jian , B., Wang, N., Sun, Y., de la Llera Moya, IM., Phillips, M. C., Rothb lat, G. H., Swaney, J. B., and Tall, A. R. (1997) J. Biol. Chem. 272, 20982-20985). In this paper we describe studies that suggest that the presence of phospholipid on acceptor particles plays an important role in modulating interaction with the SR-BI. Specifically, enrichment of serum with phospholipid resulted in marked stimulation of cholesterol efflux from cells that had higher levels of SR-BI expression, like Fu 5AH or Y1-BS1 cells, and little or no stimulation in cells with low SR -BI levels, such as Y-1 cells. Stimulation of efflux by phospholipid e nrichment was also a function of SR-BI levels in Chinese hamster ovary cells transfected with the SR-BI gene. Efflux to protein-free vesicle s prepared with 1-palmitoyl-2-oleoylphosphatidylcholine also correlate d with SR-BI levels, suggesting that phospholipid, as well as protein, influences the interaction that results in cholesterol efflux. By con trast, cholesterol efflux from a non-cell donor showed no stimulation consequent to phospholipid enrichment of the serum acceptor. These res ults may help to explain observations in the literature that document an increased risk of atherosclerosis in patients with depressed levels of HDL phospholipid even in the face of normal HDL cholesterol levels .