title: Granulocyte macrophage colony-stimulating factor regulates dendritic cell content of atherosclerotic lesions.
abstract: 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.
authors.affiliation: Department of Molecular and Medical Pharmacology, UCLA School of Medicine, Los Angeles, CA 90095, USA.
authors.forename: Zory
authors.initials: Z
authors.lastname: Shaposhnik
authors.forename: Xuping
authors.initials: X
authors.lastname: Wang
authors.forename: Michael
authors.initials: M
authors.lastname: Weinstein
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Bennett
authors.forename: Aldons J
authors.initials: AJ
authors.lastname: Lusis
mesh_terms: 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
chemical_list: D016178:Granulocyte-Macrophage Colony-Stimulating Factor