Document Detail

Induction of murine macrophage growth by oxidized low density lipoprotein is mediated by granulocyte macrophage colony-stimulating factor.
MedLine Citation:
PMID:  9774454     Owner:  NLM     Status:  MEDLINE    
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.
T Biwa; H Hakamata; M Sakai; A Miyazaki; H Suzuki; T Kodama; M Shichiri; S Horiuchi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  273     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  1998 Oct 
Date Detail:
Created Date:  1998-11-12     Completed Date:  1998-11-12     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  28305-13     Citation Subset:  IM    
Department of Biochemistry, Kumamota University School of Medicine, Kumamota 860-0811, Japan.
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MeSH Terms
Cell Division
Culture Media, Conditioned
Dose-Response Relationship, Drug
Enzyme Activation
Granulocyte-Macrophage Colony-Stimulating Factor / antagonists & inhibitors,  secretion*
Interleukin-3 / antagonists & inhibitors
Interleukin-5 / antagonists & inhibitors
Lipoproteins, LDL / pharmacology*
Lysophosphatidylcholines / metabolism
Macrophage Colony-Stimulating Factor / antagonists & inhibitors
Macrophages, Peritoneal / drug effects*
Mice, Knockout
Naphthalenes / pharmacology
Protein Kinase C / metabolism
Receptors, Immunologic / genetics
Receptors, Scavenger
Scavenger Receptors, Class A
Signal Transduction
Reg. No./Substance:
0/Culture Media, Conditioned; 0/Interleukin-3; 0/Interleukin-5; 0/Lipoproteins, LDL; 0/Lysophosphatidylcholines; 0/Msr1 protein, mouse; 0/Naphthalenes; 0/Receptors, Immunologic; 0/Receptors, Scavenger; 0/Scavenger Receptors, Class A; 0/calphostin complex; 0/oxidized low density lipoprotein; 81627-83-0/Macrophage Colony-Stimulating Factor; 83869-56-1/Granulocyte-Macrophage Colony-Stimulating Factor; EC Kinase C

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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