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(Received for publication, January 23, 1996, and in revised form, June 1, 1996)
From the § Department of Biochemistry and
We have recently demonstrated that the growth of
murine macrophages is induced by oxidized low density lipoprotein
(Ox-LDL) and that lysophosphatidylcholine (lyso-PC), a major
phospholipid component of Ox-LDL, plays an essential role in its
mitogenic effect. The present study was undertaken to further
characterize the role of the macrophage scavenger receptor (MSR) in
Ox-LDL-induced macrophage growth. The growth-stimulating effect of
Ox-LDL on murine resident peritoneal macrophages was inhibited by
maleylated bovine serum albumin (maleyl-BSA), a non-lipoprotein ligand
for MSR but a poor carrier of lyso-PC, while maleyl-BSA itself failed
to induce macrophage growth even in the presence of lyso-PC. Moreover,
it competitively inhibited the endocytic uptake of
125I-Ox-LDL and the specific uptake of lyso-PC by MSR,
whereas nonspecific lyso-PC transfer to cells was not affected.
Furthermore, the Ox-LDL-induced cell growth of peritoneal macrophages
obtained from MSR knockout mice was significantly weaker than that of
macrophages obtained from their wild-type littermates. Our results
suggest that the MSR is an important and efficient internalization
pathway for lyso-PC in Ox-LDL-induced macrophage growth.
Volume 271, Number 44,
Issue of November 1, 1996
pp. 27346-27352
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.
,
,
and
Department of Metabolic Medicine, Kumamoto University
School of Medicine, Honjo 2-2-1, Kumamoto 860, Japan and ¶ The
Third Department of Internal Medicine, Faculty of Medicine, The
University of Tokyo, Tokyo 113, Japan
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