Severe reduction in leukocyte adhesion and monocyte extravasation in mice deficient in CC chemokine receptor 2.
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 approximately 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 beta-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.
Kuziel
W A
WA
Department of Pathology and Laboratory Medicine, University of North Carolina Medical School, 702 Brinkhous-Bullitt Building, Chapel Hill, NC 27599-7525, USA.
Morgan
S J
SJ
Dawson
T C
TC
Griffin
S
S
Smithies
O
O
Ley
K
K
Maeda
N
N
D000818:Animals; D002448:Cell Adhesion; D002465:Cell Movement; D018932:Chemokine CCL2 / Q000502:physiology; D006099:Granuloma / Q000139:chemically induced; D007962:Leukocytes / Q000502:physiology*; D008099:Liver / Q000473:pathology; D008264:Macrophages / Q000502:physiology; D051379:Mice; D008817:Mice, Mutant Strains; D008833:Microcirculation / Q000502:physiology; D009000:Monocytes / Q000502:physiology*; D009132:Muscles / Q000098:blood supply; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000172:deficiency*
C515335:Ccr2 protein, mouse; D018932:Chemokine CCL2; D054390:Receptors, CCR2; D019707:Receptors, Chemokine