Document Detail


Oxidized LDL can induce macrophage survival, DNA synthesis, and enhanced proliferative response to CSF-1 and GM-CSF.
MedLine Citation:
PMID:  9888871     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Modification of low density lipoprotein (LDL), eg, by oxidation, has been proposed as being important for the formation of foam cells and therefore for the development of atherosclerotic plaques. There are a number of reports showing that macrophage-derived foam cells can proliferate in both human and animal lesions, particularly in the early phase of the disease and possibly involving macrophage-colony stimulating factor (M-CSF, or CSF-1). We studied the in vitro effects of oxidized LDL (ox-LDL) on murine bone marrow-derived macrophages (BMMs), a cell population with a high proliferative capacity in vitro in response to CSF-1 and a dependence for survival on the presence of this growth factor. We report here that treatment of BMMs with low doses of ox-LDL, but not with native LDL, led to cell survival, DNA synthesis, and an enhanced response to the proliferative actions of CSF-1 and granulocyte macrophage-CSF (GM-CSF); the effects were dependent on the degree of LDL oxidation. For CSF-1, a synergistic effect was noticeable at suboptimal doses. The effect of ox-LDL occurred even in the absence of endogenous CSF-1 or GM-CSF. Our findings suggest that ox-LDL, and possibly other modified forms of LDL, could maintain macrophage (and foam cell) survival and therefore lengthen their tenure in a plaque; the modified LDL could also cause local macrophage proliferation or "prime" them so that they could proliferate better in response to CSF-1 (and GM-CSF) concentrations that may be present in the atheroma.
Authors:
J A Hamilton; D Myers; W Jessup; F Cochrane; R Byrne; G Whitty; S Moss
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Arteriosclerosis, thrombosis, and vascular biology     Volume:  19     ISSN:  1079-5642     ISO Abbreviation:  Arterioscler. Thromb. Vasc. Biol.     Publication Date:  1999 Jan 
Date Detail:
Created Date:  1999-04-20     Completed Date:  1999-04-20     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9505803     Medline TA:  Arterioscler Thromb Vasc Biol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  98-105     Citation Subset:  IM    
Affiliation:
Inflammation Research Centre, University of Melbourne, The Royal Melbourne Hospital, Parkville, Australia. j.hamilton@medicine.unimelb.edu.au
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MeSH Terms
Descriptor/Qualifier:
Animals
Bone Marrow Cells
Cell Division / drug effects*
Cell Survival / drug effects
DNA / biosynthesis*
Dose-Response Relationship, Drug
Drug Synergism
Female
Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology*
Kinetics
Lipoproteins, LDL / administration & dosage,  pharmacology*
Macrophage Colony-Stimulating Factor / pharmacology*
Macrophages / cytology,  drug effects*,  physiology
Male
Mice
Mice, Inbred CBA
Chemical
Reg. No./Substance:
0/Lipoproteins, LDL; 0/oxidized low density lipoprotein; 81627-83-0/Macrophage Colony-Stimulating Factor; 83869-56-1/Granulocyte-Macrophage Colony-Stimulating Factor; 9007-49-2/DNA

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


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