ArticlePloS one2015
Localized CCR2 Activation in the Bone Marrow Niche Mobilizes Monocytes by Desensitizing CXCR4.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
48 citing papers in PubMed, 65 citations in OpenAlex.
- Bone marrow myelopoiesis dysfunction in Alzheimer's disease limits monocyte homing to the brain and drives disease progression.Nature neuroscience · 2026Article
- Jurkat T-Cell Antigen-Independent Elimination of PMA-Activated Neuroblastoma Cells Is Triggered by CCL2/CCR2, Depends Upon Lipid Raft LFA1/ICAM1 Immune Synapses, Is Mediated by m-TRAIL and Is Augmented by the TrkAIII Oncoprotein.International journal of molecular sciences · 2026Article
- Maternal Obesity Reprograms Differentiation Trajectories of Fetal Hematopoietic Stem and Progenitor Cells Through Altered Inflammatory Signaling.bioRxiv : the preprint server for biology · 2026Article
- CX3CR1 and CCR2: dynamic myeloid cell states across inflammatory diseases with implications for oral health and disease.Frontiers in immunology · 2026Review
- Skull bone marrow and skull meninges channels: redefining the landscape of central nervous system immune surveillance.Cell death & disease · 2025Review
- The immunological perspective of major depressive disorder: unveiling the interactions between central and peripheral immune mechanisms.Journal of neuroinflammation · 2025Review
- Brd4 modulates metabolic endotoxemia-induced inflammation by regulating colonic macrophage infiltration in high-fat diet-fed mice.Communications biology · 2024Article
- Nasal virus infection induces asthma exacerbation through B-cell-dependent recruitment of inflammatory monocytes.International forum of allergy & rhinology · 2024Article
- Brain Resident Ly6CAging and disease · 2024Article
- CCR2 cooperativity promotes hematopoietic stem cell homing to the bone marrow.Science advances · 2024Article
- C-C motif chemokine receptor 2 and 7 synergistically control inflammatory monocyte recruitment but the infecting virus dictates monocyte function in the brain.Communications biology · 2024Article
- Macrophage profiling in atherosclerosis: understanding the unstable plaque.Basic research in cardiology · 2024Review
- Indole-3-carbinol attenuates lipopolysaccharide-induced acute respiratory distress syndrome through activation of AhR: role of CCR2+ monocyte activation and recruitment in the regulation of CXCR2+ neutrophils in the lungs.Frontiers in immunology · 2024Article
- Unravelling monocyte functions: from the guardians of health to the regulators of disease.Discovery immunology · 2024Review
- Central regulation of stress-evoked peripheral immune responses.Nature reviews. Neuroscience · 2023Review
- TLR7 activation at epithelial barriers promotes emergency myelopoiesis and lung antiviral immunity.eLife · 2023Article
- Mature B cells and mesenchymal stem cells control emergency myelopoiesis.Life science alliance · 2023Article
- Phenotypic and functional heterogeneity of monocytes in health and cancer in the era of high dimensional technologies.Blood reviews · 2023Review
- HIV vaccine candidate efficacy in female macaques mediated by cAMP-dependent efferocytosis and V2-specific ADCC.Nature communications · 2023Article
- Characteristics, polarization and targeted therapy of mononuclear macrophages in rheumatoid arthritis.American journal of translational research · 2023Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Inflammatory (classical) monocytes residing in the bone marrow must enter the bloodstream in order to combat microbe infection. These monocytes express high levels of CCR2, a chemokine receptor whose activation is required for them to exit the bone marrow. How CCR2 is locally activated in the bone marrow and how their activation promotes monocyte egress is not understood. Here, we have used double transgenic lines that can visualize CCR2 activation in vivo and show that its chemokine ligand CCL2 is acutely released by stromal cells in the bone marrow, which make direct contact with CCR2-expressing monocytes. These monocytes also express CXCR4, whose activation immobilizes cells in the bone marrow, and are in contact with stromal cells expressing CXCL12, the CXCR4 ligand. During the inflammatory response, CCL2 is released and activates the CCR2 on neighboring monocytes. We demonstrate that acutely isolated bone marrow cells co-express CCR2 and CXCR4, and CCR2 activation desensitizes CXCR4. Inhibiting CXCR4 by a specific receptor antagonist in mice causes CCR2-expressing cells to exit the bone marrow in absence of inflammatory insults. Taken together, these results suggest a novel mechanism whereby the local activation of CCR2 on monocytes in the bone marrow attenuates an anchoring signalling provided by CXCR4 expressed by the same cell and mobilizes the bone marrow monocyte to the blood stream. Our results also provide a generalizable model that cross-desensitization of chemokine receptors fine-tunes cell mobility by integrating multiple chemokine signals.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.