Critical roles for CCR2 and MCP-3 in monocyte mobilization from bone marrow and recruitment to inflammatory sites
Open accessAbstract
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.
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The CCL2-CCR2 and CX3CL1-CX3CR1 chemotactic axes are two ligand-receptor signaling pathways that recruit monocytes to sites of inflammation, including the brain.
“the CCL2-CCR2 and CX3CL1-CX3CR1 chemotactic axis are two ligand-receptor signaling pathways that recruit monocytes to sites of inflammation (Auffray et al, 2007;Tsou et al, 2007), including the brain (D' Mello et al, 2009).”
From Repeated Social Defeat, Neuroinflammation, and Behavior: Monocytes Carry the Signal (2017) · cites this paper as Tsou et al, 2007
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- Authors
- Tsou, C.-L., Peters, W., Si, Y., Slaymaker, S., Aslanian, A. M., Weisberg, S. P., Mack, M., & Charo, I. F.
- Affiliations
- University of California, San Francisco (US)
- Gladstone Institutes (US)
- Columbia University Irving Medical Center (US)
- Columbia University (US)
- Corresponding author
- Charo, Israel F.
- Venue
- Journal of Clinical Investigation
- Published
- 2007-04-02
- Volume
- 117
- Issue
- 4
- Pages
- 902-909
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC1810572
- OpenAlex
- W2010472544
- Cited by
- 1,152
- References
- 34
- Citations by year
- 2026: 53 · 2025: 55 · 2024: 75 · 2023: 54 · 2022: 70 · 2021: 64 · 2020: 61 · 2019: 46 · 2018: 57 · 2017: 68 · 2016: 80 · 2015: 59 · 2014: 66 · 2013: 69 · 2012: 55
- FWCI
- 26.15
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (R01HL063894, R01HL052773, 5R01 HL52773-12, R01 HL63894-07)
- Topics
- Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Life Sciences › Immunology and Microbiology › Immunology › Inflammation biomarkers and pathways
- Keywords
- CCR2, MCP-3, MCP-1, monocyte mobilization, monocyte recruitment, chemokines, bone marrow, inflammation, CCR2-deficient mice
- MeSH terms
- Animals, Blood Cell Count, Bone Marrow Cells, Humans, Inflammation, Monocytes, Polymorphism, Genetic, Bone Marrow Transplantation, Mice, Knockout, Chemokines, Monocyte Chemoattractant Proteins, Adoptive Transfer, Receptors, Chemokine, Mice, Receptors, CCR2, Chemokine CCL7
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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