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J Biol Chem, Vol. 273, Issue 43, 28305-28313, October 23, 1998
From the We have examined whether certain secreted
factor(s) is involved in oxidized low density lipoprotein
(Ox-LDL)-induced murine macrophage growth. An antibody against
granulocyte-macrophage colony-stimulating factor (GM-CSF) effectively
inhibited Ox-LDL-induced macrophage growth by >80%. Ox-LDL as well as
phospholipase A2-treated acetylated LDL enhanced
mRNA levels and protein release of GM-CSF from macrophages, while
neither acetylated LDL nor lysophosphatidylcholine (lyso-PC) showed
such effects. The maximal induction of GM-CSF by Ox-LDL was noted at
4 h, followed by a time-dependent decrease to a basal
level within 24 h. Ox-LDL-induced macrophage growth was inhibited
by 75% by replacement of the culture medium at 24 h by a fresh
medium containing the same concentration of Ox-LDL, when GM-CSF had
already returned to the basal level. Thus, a cytokine(s) other than
GM-CSF is also expected to participate in Ox-LDL-induced macrophage
growth in a later phase. The Ox-LDL-induced GM-CSF release was
inhibited by calphostin C, a protein kinase C inhibitor, and was
significantly reduced in macrophages from the knockout mice lacking
class A, type I and type II macrophage scavenger receptors
(MSR-AI/AII). These results taken together indicate that effective
endocytosis of lyso-PC of Ox-LDL by macrophages through MSR-AI/AII and
subsequent protein kinase C activation have led to GM-CSF release into
the medium which may play a priming role in conjunction with other
cytokines in Ox-LDL-induced macrophage growth.
Induction of Murine Macrophage Growth by Oxidized Low Density
Lipoprotein Is Mediated by Granulocyte Macrophage
Colony-stimulating Factor
§,,,
,
Department of Biochemistry and
§ Department of Metabolic Medicine, Department of Molecular Biology and
Medicine,
Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.
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