| First Author | Zernecke A | Year | 2006 |
| Journal | Blood | Volume | 107 |
| Issue | 11 | Pages | 4240-3 |
| PubMed ID | 16467202 | Mgi Jnum | J:128843 |
| Mgi Id | MGI:3768182 | Doi | 10.1182/blood-2005-09-3922 |
| Citation | Zernecke A, et al. (2006) Deficiency in CCR5 but not CCR1 protects against neointima formation in atherosclerosis-prone mice: involvement of IL-10. Blood 107(11):4240-3 |
| abstractText | 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. |
