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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

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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 1

FACS analysis of murine peripheral blood leukocytes.

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FACS analysis of murine peripheral blood leukocytes.
(A) After lysis of ...
(A) After lysis of red blood cells, leukocytes were stained with antibodies specific to 7/4 and Ly-6G to reveal a population of pure monocytes (7/4briLy-6G–), a population of pure neutrophils (7/4briLy-6G+), and a mixed population of monocytes, T cells, and B cells (7/4dimLy-6G–). (B and C) Expression levels of F4/80 (B) and CCR2 (C) on populations of monocytes (7/4briLy-6G–), neutrophils (7/4briLy-6G+), and mixed leukocytes (7/4dimLy-6G–). Gates were set so that no cells were included in the absence of the primary antibody. Numbers are percentages of total leukocytes in each population. (D) Expression of CCR2 on monocytes (7/4briLy-6G–) and mixed leukocytes (7/4dimLy-6G–).

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