4.7 Article

Granulocyte macrophage colony-stimulating factor regulates dendritic cell content of atherosclerotic lesions

Journal

ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
Volume 27, Issue 3, Pages 621-627

Publisher

LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/01.ATV.0000254673.55431.e6

Keywords

atherosclerosis; dendritic cells; elastin; GM-CSF; macrophages

Funding

  1. NCI NIH HHS [P30 CA016042, CA-16042] Funding Source: Medline
  2. NHLBI NIH HHS [P01 HL030568, P01 HL030568-230009, P01 HL-30568, P01 HL030568-230011] Funding Source: Medline
  3. NIAID NIH HHS [AI-28697, P30 AI028697] Funding Source: Medline

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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. Methods and 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. Conclusion - 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.

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