Critical roles for CCR2 and MCP-3 in monocyte mobilization from bone marrow and recruitment to inflammatory sites
Chia-Lin Tsou, … , Matthias Mack, Israel F. Charo
Chia-Lin Tsou, … , Matthias Mack, Israel F. Charo
Published April 2, 2007
Citation Information: J Clin Invest. 2007;117(4):902-909. https://doi.org/10.1172/JCI29919.
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Research Article Inflammation

Critical roles for CCR2 and MCP-3 in monocyte mobilization from bone marrow and recruitment to inflammatory sites

Abstract

Monocyte recruitment to sites of inflammation is regulated by members of the chemokine family of chemotactic cytokines. However, the mechanisms that govern the migration of monocytes from bone marrow to blood and from blood to inflamed tissues are not well understood. Here we report that CC chemokine receptor 2 (CCR2) is highly expressed on a subpopulation of blood monocytes whose numbers are markedly decreased in CCR2–/– mice. In bone marrow, however, CCR2–/– mice had an increased number of monocytes, suggesting that CCR2 is critical for monocyte egress. Intravenous infusion of ex vivo–labeled WT or CCR2–/– bone marrow into WT recipient mice demonstrated that CCR2 is necessary for efficient monocyte recruitment from the blood to inflamed tissue. Analysis of mice lacking monocyte chemoattractant protein–1 (MCP-1), MCP-3, MCP-5, or MCP-2 plus MCP-5 revealed that MCP-3 and MCP-1 are the CCR2 agonists most critical for the maintenance of normal blood monocyte counts. These findings provide evidence that CCR2 and MCP-3/MCP-1 are critical for monocyte mobilization and suggest new roles for monocyte chemoattractants in leukocyte homeostasis.

Authors

Chia-Lin Tsou, Wendy Peters, Yue Si, Sarah Slaymaker, Ara M. Aslanian, Stuart P. Weisberg, Matthias Mack, Israel F. Charo

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Figure 3

Effect of a high-fat diet on blood monocytes in CCR2+/+ and CCR2–/– mice.

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Effect of a high-fat diet on blood monocytes in CCR2+/+ and CCR2–/– mice...
Mice were fed regular laboratory chow or a high-fat Western diet for 45 weeks before sacrifice. (A) Typical FACS plots of total blood leukocytes obtained from CCR2+/+ and CCR2–/– mice on the Western diet and stained for 7/4 and Ly-6G as described in Figure 1. (B) Quantification of the FACS data showed an increase in the 7/4bri (monocyte) population in CCR2+/+, but not in CCR2–/–, mice in response to the high-fat diet. The mixed leukocyte population (7/4dim) had a more modest increase. Values are mean ± SD. n = 4 mice per genotype. *P < 0.05.