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Kuziel, W.A. et al. Severe reduction in leukocyte adhesion and monocyte extravasation in mice deficient in CC chemokine receptor 2. Proc. Natl. Acad. Sci. USA 94, 12053-12058

Department of Pathology and Laboratory Medicine, University of North Carolina Medical School, 702 Brinkhous-Bullitt Building, Chapel Hill, NC 27599-7525, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.81). 10/1997; 94(22):12053-12058. DOI: 10.1073/pnas.94.22.12053
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ABSTRACT CC chemokine receptor 2 (CCR2) is a prominent receptor for the monocyte chemoattractant protein (MCP) group of CC chemokines.
Mice generated by gene targeting to lack CCR2 exhibit normal leukocyte rolling but have a pronounced defect in MCP-1-induced
leukocyte firm adhesion to microvascular endothelium and reduced leukocyte extravasation. Constitutive macrophage trafficking
into the peritoneal cavity was not significantly different between CCR2-deficient and wild-type mice. However, after intraperitoneal
thioglycollate injection, the number of peritoneal macrophages in CCR2-deficient mice did not rise above basal levels, whereas
in wild-type mice the number of macrophages at 36 h was ≈3.5 times the basal level. The CCR2-deficient mice showed enhanced
early accumulation and delayed clearance of neutrophils and eosinophils. However, by 5 days neutrophils and eosinophils in
both CCR2-deficient and wild-type mice had returned to near basal levels, indicating that resolution of this inflammatory
response can occur in the absence of macrophage influx and CCR2-mediated activation of the resident peritoneal macrophages.
After intravenous injection with yeast β-glucan, wild-type mice formed numerous large, well-defined granulomas throughout
the liver parenchyma, whereas CCR2-deficient mice had much fewer and smaller granulomas. These results demonstrate that CCR2
is a major regulator of induced macrophage trafficking in vivo.

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