Granulocyte macrophage colony-stimulating factor regulates dendritic cell content of atherosclerotic lesions.
OBJECTIVE
Recent evidence suggests that dendritic cells may play an important role in atherosclerosis. Based primarily on previous in vitro studies, we hypothesized that granulocyte macrophage colony-stimulating factor (GM-CSF)-deficient mice would have decreased dendritic cells in lesions.


RESULTS
To test this, we characterized gene targeted GM-CSF(-/-) mice crossed to hypercholesterolemic low-density lipoprotein receptor null mice. Our results provide conclusive evidence that GM-CSF is a major regulator of dendritic cell formation in vivo. Aortic lesion sections in GM-CSF(-/-) low-density lipoprotein receptor null animals showed a dramatic 60% decrease in the content of dendritic cells as judged by CD11c staining but no change in the overall content of monocyte-derived cells. The GM-CSF-deficient mice exhibited a significant 20% to 50% decrease in the size of aortic lesions, depending on the location of the lesions. Other prominent changes in GM-CSF(-/-) mice were decreased lesional T cell content, decreased autoantibodies to oxidized lipids, and striking disruptions of the elastin fibers adjacent to the lesion.


CONCLUSIONS
Given that GM-CSF is dramatically induced by oxidized lipids in endothelial cells, our data suggest that GM-CSF serves to regulate dendritic cell formation in lesions and that this, in turn, influences inflammation, plaque growth and possibly plaque stability.
Shaposhnik
Zory
Z
Department of Molecular and Medical Pharmacology, UCLA School of Medicine, Los Angeles, CA 90095, USA.
Wang
Xuping
X
Weinstein
Michael
M
Bennett
Brian J
BJ
Lusis
Aldons J
AJ
D000818:Animals; D050197:Atherosclerosis / Q000503:physiopathology*; D002452:Cell Count; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000473:pathology / Q000502:physiology*; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012016:Reference Values; D012680:Sensitivity and Specificity
D016178:Granulocyte-Macrophage Colony-Stimulating Factor