Journal article
Genetic Deletion of Chemokine Receptor Ccr6 Decreases Atherogenesis in ApoE-deficient Mice
Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland1
The chemokine receptor Ccr6 is a G protein-coupled receptor expressed on various types of leukocytes identified in mouse atherosclerotic lesions. Recent evidence suggests that both CCR6 and its ligand CCL20 are also present in human atheroma; however, their functional roles in atherogenesis remain undefined.
To delineate the role of Ccr6 in atherogenesis in the apolipoprotein E-deficient (ApoE−/−) mouse model of atherosclerosis. Both Ccr6 and Ccl20 are expressed in atherosclerotic aorta from ApoE−/− mice. Aortic lesion area in Ccr6−/− ApoE−/− mice was ~40% and ~30% smaller than in Ccr6+/+ApoE−/− mice at 16 and 24 weeks of age, respectively.
Transplantation of bone marrow from Ccr6−/− mice into ApoE−/− mice resulted in ~40% less atherosclerotic lesion area than for bone marrow from Ccr6+/+ mice; lesions in Ccr6−/− ApoE−/− mice had 44% less macrophage content compared to lesions in Ccr6+/+ApoE−/− mice. Ccr6 was expressed on a subset of primary mouse monocytes.
Accordingly, Ccl20 induced chemotaxis of primary monocytes from wild type but not Ccr6−/− mice; moreover, Ccl20 induced monocytosis in ApoE−/− mice in vivo. Consistent with this, we observed 30% fewer monocytes in circulating blood of Ccr6−/− ApoE−/− mice, mainly due to fewer CD11b+Ly6Chigh inflammatory monocytes.
Ccr6 promotes atherosclerosis in ApoE-deficient mice, which may be due in part to Ccr6 support of normal monocyte levels in blood, as well as direct Ccr6-dependent monocyte migration.
Language: | English |
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Publisher: | American Heart Association, Inc. |
Year: | 2012 |
Pages: | 374-381 |
ISSN: | 15244571 and 00097330 |
Types: | Journal article |
DOI: | 10.1161/CIRCRESAHA.111.242578 |
Animals Antigens, Ly Aorta Aortic Diseases Apolipoproteins E Atherosclerosis Bone Marrow Transplantation CCL20 protein, mouse CCR6 protein, mouse CD11b Antigen Cell Line Chemokine CCL20 Chemotaxis, Leukocyte Disease Models, Animal Female Gene Deletion Leukocyte Count Ly-6C antigen, mouse Macrophages Mice Mice, Inbred C57BL Mice, Knockout Monocytes Receptors, CCR6 Time Factors aorta atherosclerosis inflammation monocytes