BIOMAT Database Logo BIOMAT Database Logo

Genetic deletion of chemokine receptor Ccr6 decreases atherogenesis in ApoE-deficient mice. 2011

Wuzhou Wan, and Jean K Lim, and Michail S Lionakis, and Aymeric Rivollier, and David H McDermott, and Brian L Kelsall, and Joshua M Farber, and Philip M Murphy
Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

BACKGROUND 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. OBJECTIVE Our objective was to delineate the role of Ccr6 in atherogenesis in the apolipoprotein E-deficient (ApoE(-/-)) mouse model of atherosclerosis. RESULTS 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 than 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 because of fewer CD11b(+)Ly6C(high) inflammatory monocytes. CONCLUSIONS 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.

UI MeSH Term Description Entries
D007958 Leukocyte Count The number of WHITE BLOOD CELLS per unit volume in venous BLOOD. A differential leukocyte count measures the relative numbers of the different types of white cells. Blood Cell Count, White,Differential Leukocyte Count,Leukocyte Count, Differential,Leukocyte Number,White Blood Cell Count,Count, Differential Leukocyte,Count, Leukocyte,Counts, Differential Leukocyte,Counts, Leukocyte,Differential Leukocyte Counts,Leukocyte Counts,Leukocyte Counts, Differential,Leukocyte Numbers,Number, Leukocyte,Numbers, Leukocyte
D008264 Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.) Bone Marrow-Derived Macrophages,Monocyte-Derived Macrophages,Macrophage,Macrophages, Monocyte-Derived,Bone Marrow Derived Macrophages,Bone Marrow-Derived Macrophage,Macrophage, Bone Marrow-Derived,Macrophage, Monocyte-Derived,Macrophages, Bone Marrow-Derived,Macrophages, Monocyte Derived,Monocyte Derived Macrophages,Monocyte-Derived Macrophage
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D009000 Monocytes Large, phagocytic mononuclear leukocytes produced in the vertebrate BONE MARROW and released into the BLOOD; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. Monocyte
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D002634 Chemotaxis, Leukocyte The movement of leukocytes in response to a chemical concentration gradient or to products formed in an immunologic reaction. Leukotaxis,Leukocyte Chemotaxis
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D005260 Female Females
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000950 Antigens, Ly A group of lymphocyte surface antigens located on mouse LYMPHOCYTES. Specific Ly antigens are useful markers for distinguishing subpopulations of lymphocytes. Ly Antigens

Related Publications

Wuzhou Wan, and Jean K Lim, and Michail S Lionakis, and Aymeric Rivollier, and David H McDermott, and Brian L Kelsall, and Joshua M Farber, and Philip M Murphy
Genetic deletion of chemokine receptor Ccr7 exacerbates atherogenesis in ApoE-deficient mice.
March 2013, Cardiovascular research,
Wuzhou Wan, and Jean K Lim, and Michail S Lionakis, and Aymeric Rivollier, and David H McDermott, and Brian L Kelsall, and Joshua M Farber, and Philip M Murphy
Regulation of atherogenesis by chemokine receptor CCR6.
July 2011, Trends in cardiovascular medicine,
Wuzhou Wan, and Jean K Lim, and Michail S Lionakis, and Aymeric Rivollier, and David H McDermott, and Brian L Kelsall, and Joshua M Farber, and Philip M Murphy
Impact of myeloid RIPK1 gene deletion on atherogenesis in ApoE-deficient mice.
April 2021, Atherosclerosis,
Wuzhou Wan, and Jean K Lim, and Michail S Lionakis, and Aymeric Rivollier, and David H McDermott, and Brian L Kelsall, and Joshua M Farber, and Philip M Murphy
Dyslipidemia, steatohepatitis and atherogenesis in lipodystrophic apoE deficient mice with Seipin deletion.
March 2018, Gene,
Wuzhou Wan, and Jean K Lim, and Michail S Lionakis, and Aymeric Rivollier, and David H McDermott, and Brian L Kelsall, and Joshua M Farber, and Philip M Murphy
Atypical chemokine receptor 1 deficiency reduces atherogenesis in ApoE-knockout mice.
June 2015, Cardiovascular research,
Wuzhou Wan, and Jean K Lim, and Michail S Lionakis, and Aymeric Rivollier, and David H McDermott, and Brian L Kelsall, and Joshua M Farber, and Philip M Murphy
Myeloid-Specific Deletion of Diacylglycerol Lipase α Inhibits Atherogenesis in ApoE-Deficient Mice.
January 2016, PloS one,
Wuzhou Wan, and Jean K Lim, and Michail S Lionakis, and Aymeric Rivollier, and David H McDermott, and Brian L Kelsall, and Joshua M Farber, and Philip M Murphy
Thalidomide inhibits early atherogenesis in apoE-deficient mice.
January 2003, APMIS. Supplementum,
Wuzhou Wan, and Jean K Lim, and Michail S Lionakis, and Aymeric Rivollier, and David H McDermott, and Brian L Kelsall, and Joshua M Farber, and Philip M Murphy
Augmented atherogenesis in LDL receptor deficient mice lacking both macrophage ABCA1 and ApoE.
January 2011, PloS one,
Wuzhou Wan, and Jean K Lim, and Michail S Lionakis, and Aymeric Rivollier, and David H McDermott, and Brian L Kelsall, and Joshua M Farber, and Philip M Murphy
A novel CCR2 antagonist inhibits atherogenesis in apoE deficient mice by achieving high receptor occupancy.
March 2017, Scientific reports,
Wuzhou Wan, and Jean K Lim, and Michail S Lionakis, and Aymeric Rivollier, and David H McDermott, and Brian L Kelsall, and Joshua M Farber, and Philip M Murphy
Deficiency of PXR decreases atherosclerosis in apoE-deficient mice.
September 2011, Journal of lipid research,
Copied contents to your clipboard!