Jh. Han et al., NATIVE AND MODIFIED LOW-DENSITY LIPOPROTEINS INCREASE THE FUNCTIONAL EXPRESSION OF THE MACROPHAGE CLASS-B SCAVENGER RECEPTOR, CD36, The Journal of biological chemistry, 272(34), 1997, pp. 21654-21659
The uptake of oxidized low density lipoprotein (OxLDL) by macrophages
is a key event implicated in the initiation and development of atheros
clerotic lesions, Two macrophage surface receptors, CD36 (a class B sc
avenger receptor) and the macrophage scavenger receptor (a class A sca
venger receptor), have been identified as the major receptors that bin
d and internalize OxLDL. Expression of CD36 in monocyte/macrophages in
tissue culture is dependent both on the differentiation state as well
as exposure to soluble mediators (cytokines and growth factors), The
regulatory mechanisms of this receptor in vivo are undetermined as is
the role of lipoproteins themselves in modulating CD36 expression. We
studied the effect of lipoproteins, native LDL and modified LDL (acety
lated LDL (AcLDL) and OxLDL) on the expression of CD36 in J774 cells,
a murine macrophage cell line, Exposure to lipoproteins resulted in a
marked induction of CD36 mRNA expression (4-8-fold), Time course studi
es showed that maximum induction was observed 2 h after treatment with
AcLDL and at 4 h with LDL and OxLDL, Increased expression of CD36 mRN
A persisted for 24 h with each treatment group, Induction of CD36: mRN
A expression was paralleled by an increase in CD36 protein as determin
ed by Western blot with the greatest induction by OxLDL (4-fold), In t
he presence of actinomycin D, treatment of macrophages with LDL, AcLDL
, or OxLDL did not affect. CD36 mRNA stability, implying that CD36 mRN
A was transcriptionally regulated by lipoproteins. To determine the me
chanism(s) by which lipoproteins increased expression of CD36 we evalu
ated the effects of lipoprotein components on CD36 mRNA. expression, A
poB 100 increased CD36 mRNA expression significantly, whereas phosphol
ipid/cholesterol liposomes had. less effect, Incubation of macrophages
with bovine serum albumin or HDL reduced expression of CD36 mRNA in a
dose-dependent manner. Finally, to evaluate the in vivo relevance of
the induction of CD36 mRNA expression by lipoproteins, peritoneal macr
ophages were isolated from mice following intraperitoneal injection of
lipoproteins. Macrophage expression of CD36 mRNA was significantly in
creased by LDL, AcLDL, or OxLDL in relation to mice infused with phosp
hate-buffered saline, with OxLDL causing the greatest induction (8-fol
d). This is the first demonstration that exposure to free and esterifi
ed lipids augments functional expression of the class B scavenger rece
ptor, CD36, These data imply that lipoproteins can further contribute
to foam cell development in atherosclerosis by up-regulating a major O
xLDL receptor.