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  • Deficiency in CCR5 but not CCR1 protects against neointima formation in atherosclerosis-prone mice: involvement of IL-10.

Deficiency in CCR5 but not CCR1 protects against neointima formation in atherosclerosis-prone mice: involvement of IL-10.

Blood (2006-02-10)
Alma Zernecke, Elisa A Liehn, Ji-Liang Gao, William A Kuziel, Philip M Murphy, Christian Weber
ABSTRACT

The chemokine RANTES has been implicated in neointimal hyperplasia after arterial injury. We analyzed the differential role of the RANTES receptors CCR1 and CCR5 by genetic deletion in apolipoprotein E-deficient mice. Deficiency in CCR5 significantly reduced neointimal area after arterial wire injury, associated with a decrease in macrophages, CD3(+) T lymphocytes, and CCR2(+) cells. In contrast, CCR1 deficiency did not affect neointimal area or cell content. Deletion of CCR5 entailed an up-regulation of the anti-inflammatory cytokine interleukin 10 (IL-10) in neointimal smooth muscle cells, and its antibody blockade reversed effects in CCR5(-/-) mice. Conversely, proinflammatory interferon gamma was increased in the neointima of CCR1(-/-) mice, and its blockade unmasked a reduction in macrophage recruitment. Our data indicate that CCR5 is more crucial than CCR1 for neointimal plaque formation, and that its attenuation in CCR5(-/-) mice is due to an atheroprotective immune response involving IL-10. This harbors important implications for targeting chemokine receptors in vascular remodeling.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-Interferon-γ Antibody, clone RMMG-1, clone RMMG-1, Chemicon®, from rat