A new class of membrane-bound chemokine with a CX3C motif
Abstract
Chemokines direct the trafficking of white blood cells in immune surveillance, playing a key role in inflammatory and infectious diseases such as AIDS. All chemokines studied so far are secreted proteins of relative molecular mass approximately 7K-15K and fall into three families that are defined by a cysteine signature motif: CXC, CC and C (refs 3, 6, 7), where C is a cysteine and X any amino-acid residue. We report here the identification and characterization of a fourth human chemokine type, derived from non-haemopoietic cells and bearing a new CX3C fingerprint. Unlike other chemokine types, the polypeptide chain of the human CX3C chemokine is predicted to be part of a 373-amino-acid protein that carries the chemokine domain on top of an extended mucin-like stalk. This molecule can exist in two forms: either membrane-anchored or as a shed 95K glycoprotein. The soluble CX3C chemokine has potent chemoattractant activity for T cells and monocytes, and the cell-surface-bound protein, which is induced on activated primary endothelial cells, promotes strong adhesion of those leukocytes. The structure, biochemical features, tissue distribution and chromosomal localization of CX3C chemokine all indicate that it represents a unique class of chemokine that may constitute part of the molecular control of leukocyte traffic at the endothelium.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Chemokines are chemotactic cytokines that control recruitment of mononuclear phagocytes to sites of inflammation.
“Chemokines are chemotactic cytokines that control recruitment of mononuclear phagocytes to sites of inflammation (7).”
CX3CR1 and its ligand fractalkine have been implicated in recruitment of mononuclear phagocytes to sites of inflammation and injury and play roles in the pathogenesis of several inflammatory conditions including atherosclerosis, neuropathic pain, and asthma.
“CX3CR1 and its chemokine ligand fractalkine (CX3CL1) have been implicated in the recruitment of mononuclear phagocytes to sites of inflammation and injury (7, 10, 11) and play roles in the pathogenesis of several inflammatory conditions, including atherosclerosis (12, 13), neuropathic pain (14), and asthma (15).”
CX3CL1 can signal to CX3CR1 in a membrane bound form, or as a secreted ligand after constitutive or inducible cleavage by ADAM10 and ADAM17 metalloproteases, respectively.
“CX3CL1 can signal to CX3CR1 in a membrane bound form, or as a secreted ligand after constitutive or inducible cleavage by the ADAM10 and ADAM17 metalloproteases, respectively.16”
From CX3CR1 Deficiency Alters Microglial Activation and Reduces Beta-Amyloid Deposition in Two Alzheimer's Disease Mouse Models (2010) · cites this paper as [16]
Cites
Lymphocyte Homing and Homeostasis
Butcher, E. C., & Picker, L. J. (1996) · Science · doi:10.1126/science.272.5258.60 · Cited by 2,846 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Inflammation and Alzheimer’s disease
Akiyama, H. (2000) · Neurobiology of Aging · doi:10.1016/s0197-4580(00)00124-x · Cited by 4,514 · see citing works
Jung, S., Aliberti, J., Graemmel, P., Sunshine, M. J., Kreutzberg, G. W., Sher, A., & Littman, D. R. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.11.4106-4114.2000 · Cited by 2,632 · see citing works
The many roles of chemokines and chemokine receptors in inflammation
Charo, I. F., & Ransohoff, R. M. (2006) · New England Journal of Medicine · doi:10.1056/nejmra052723 · Cited by 2,523 · see citing works
The Biology of Chemokines and their Receptors
Rossi, D., & Zlotnik, A. (2000) · Annual Review of Immunology · doi:10.1146/annurev.immunol.18.1.217 · Cited by 2,410 · see citing works
Self-citationInflammation as a central mechanism in Alzheimer's disease
Kinney, J. W., Bemiller, S. M., Murtishaw, A. S., Leisgang, A. M., Salazar, A. M., & Lamb, B. T. (2018) · Alzheimer's & Dementia: Translational Research & Clinical Interventions · doi:10.1016/j.trci.2018.06.014 · Cited by 2,253 · see citing works
Monitoring of Blood Vessels and Tissues by a Population of Monocytes with Patrolling Behavior
Auffray, C., Fogg, D., Garfa, M., Elain, G., Join-Lambert, O., Kayal, S., Sarnacki, S., Cumano, A., Lauvau, G., & Geissmann, F. (2007) · Science · doi:10.1126/science.1142883 · Cited by 1,973 · see citing works
Harrison, J. K., Jiang, Y., Chen, S., Xia, Y., Maciejewski, D., McNamara, R. K., Streit, W. J., Salafranca, M. N., Adhikari, S., Thompson, D. A., et al. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.18.10896 · Cited by 1,176 · see citing works
Self-citationKim, Y. S., & Joh, T. H. (2006) · Experimental & Molecular Medicine · doi:10.1038/emm.2006.40 · Cited by 655 · see citing works
CX3CR1 deficiency leads to impairment of hippocampal cognitive function and synaptic plasticity
Rogers, J. T., Morganti, J. M., Bachstetter, A. D., Hudson, C. E., Peters, M. M., Grimmig, B. A., Weeber, E. J., Bickford, P. C., & Gemma, C. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.3667-11.2011 · Cited by 624 · see citing works
Lee, S., Varvel, N. H., Konerth, M. E., Xu, G., Cardona, A. E., Ransohoff, R. M., & Lamb, B. T. (2010) · The American Journal of Pathology · doi:10.2353/ajpath.2010.100265 · Cited by 539 · see citing works
Microglia activation in retinal degeneration
Langmann, T. (2007) · Journal of Leukocyte Biology · doi:10.1189/jlb.0207114 · Cited by 496 · see citing works
CX3CL1/fractalkine is released from apoptotic lymphocytes to stimulate macrophage chemotaxis
Truman, L. A., Ford, C. A., Pasikowska, M., Pound, J. D., Wilkinson, S. J., Dumitriu, I. E., Melville, L., Melrose, L. A., Ogden, C. A., Nibbs, R., et al. (2008) · Blood · doi:10.1182/blood-2008-06-162404 · Cited by 473 · see citing works
Expression of CX <sub>3</sub> CR1 chemokine receptors on neurons and their role in neuronal survival
Meucci, O., Fatatis, A., Simen, A. A., & Miller, R. J. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.090017497 · Cited by 385 · see citing works
Factors regulating microglia activation
Kierdorf, K., & Prinz, M. (2013) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2013.00044 · Cited by 360 · see citing works
Mizutani, M., Pino, P. A., Saederup, N., Charo, I. F., Ransohoff, R. M., & Cardona, A. E. (2012) · The Journal of Immunology · doi:10.4049/jimmunol.1100421 · Cited by 346 · see citing works
Microglia, seen from the CX3CR1 angle
Wolf, Y., Yona, S., Kim, K.-W., & Jung, S. (2013) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2013.00026 · Cited by 316 · see citing works
Microglia in Health and Disease
Ransohoff, R. M., & Khoury, J. E. (2016) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a020560 · Cited by 303 · see citing works
Ishida, Y., Gao, J.-L., & Murphy, P. M. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.1.569 · Cited by 310 · see citing works
Xia, M. Q., Bacskai, B. J., Knowles, R. B., Qin, S. X., & Hyman, B. T. (2000) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(00)00285-x · Cited by 269 · see citing works
Karlmark, K. R., Zimmermann, H. W., Roderburg, C., Gassler, N., Wasmuth, H. E., Luedde, T., Trautwein, C., & Tacke, F. (2010) · Hepatology · doi:10.1002/hep.23894 · Cited by 249 · see citing works
CX3CL1 reduces neurotoxicity and microglial activation in a rat model of Parkinson’s disease
Pabon, M. M., Bachstetter, A. D., Hudson, C. E., Gemma, C., & Bickford, P. C. (2011) · Journal of Neuroinflammation · doi:10.1186/1742-2094-8-9 · Cited by 241 · see citing works
Hughes, P. M., Botham, M. S., Frentzel, S., Mir, A., & Perry, V. H. (2002) · Glia · doi:10.1002/glia.10037 · Cited by 252 · see citing works
Microglia Modulate Hippocampal Neural Precursor Activity in Response to Exercise and Aging
Vukovic, J., Colditz, M. J., Blackmore, D. G., Ruitenberg, M. J., & Bartlett, P. F. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.5925-11.2012 · Cited by 241 · see citing works
Is resolution the end of inflammation?
Feehan, K. T., & Gilroy, D. W. (2019) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2019.01.006 · Cited by 229 · see citing works
Lyons, A., Lynch, A. M., Downer, E. J., Hanley, R., O’Sullivan, J. B., Smith, A., & Lynch, M. A. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.06253.x · Cited by 202 · see citing works
Rustenhoven, J., Aalderink, M., Scotter, E. L., Oldfield, R. L., Bergin, P. S., Mee, E. W., Graham, E. S., Faull, R. L. M., Curtis, M. A., Park, T. I.-H., et al. (2016) · Journal of Neuroinflammation · doi:10.1186/s12974-016-0503-0 · Cited by 201 · see citing works
On phagocytes and macular degeneration
Guillonneau, X., Eandi, C. M., Paques, M., Sahel, J.-A., Sapieha, P., & Sennlaub, F. (2017) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2017.06.002 · Cited by 185 · see citing works
Reader, B. F., Jarrett, B. L., McKim, D. B., Wohleb, E. S., Godbout, J. P., & Sheridan, J. F. (2015) · Neuroscience · doi:10.1016/j.neuroscience.2015.01.001 · Cited by 179 · see citing works
“Under homeostatic conditions within the CNS, fractalkine is highly and primarily expressed by neurons (Bazan et al., 1997; Kim et al., 2011), while the fractalkine receptor is highly expressed by microglia (Jung et al., 2000).”
BackgroundDysregulated neuronal–microglial cross-talk during aging, stress and inflammation
Jurgens, H. A., & Johnson, R. W. (2012) · Experimental Neurology · doi:10.1016/j.expneurol.2010.11.014 · Cited by 179 · see citing works
Opposing Effects of Membrane-Anchored CX3CL1 on Amyloid and Tau Pathologies via the p38 MAPK Pathway
Lee, S., Xu, G., Jay, T. R., Bhatta, S., Kim, K.-W., Jung, S., Landreth, G. E., Ransohoff, R. M., & Lamb, B. T. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.0853-14.2014 · Cited by 123 · see citing works
Fractalkine-Induced MFG-E8 Leads to Enhanced Apoptotic Cell Clearance by Macrophages
Miksa, M., Amin, D., Wu, R., Dong, W., Ravikumar, T. S., & Wang, P. (2007) · Molecular Medicine · doi:10.2119/2007-00019.miksa · Cited by 118 · see citing works
The challenges of primary biliary cholangitis: What is new and what needs to be done
Terziroli Beretta-Piccoli, B., Mieli-Vergani, G., Vergani, D., Vierling, J. M., Adams, D., Alpini, G., Banales, J. M., Beuers, U., Björnsson, E., Bowlus, C., et al. (2019) · Journal of Autoimmunity · doi:10.1016/j.jaut.2019.102328 · Cited by 114 · see citing works
Role of Chemokines in the Development and Progression of Alzheimer’s Disease
Wojcieszak, J., Kuczyńska, K., & Zawilska, J. B. (2022) · Journal of Molecular Neuroscience · doi:10.1007/s12031-022-02047-1 · Cited by 97 · see citing works
Loss of tau rescues inflammation-mediated neurodegeneration
Maphis, N., Xu, G., Kokiko-Cochran, O. N., Cardona, A. E., Ransohoff, R. M., Lamb, B. T., & Bhaskar, K. (2015) · Frontiers in Neuroscience · doi:10.3389/fnins.2015.00196 · Cited by 91 · see citing works
Hickman, S. E., Allison, E. K., Coleman, U., Kingery-Gallagher, N. D., & El Khoury, J. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.02780 · Cited by 80 · see citing works
Physical Exercise-Induced Myokines in Neurodegenerative Diseases
Lee, B., Shin, M., Park, Y., Won, S.-Y., & Cho, K. S. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22115795 · Cited by 79 · see citing works
Acute Brain Injury Triggers MyD88-Dependent, TLR2/4-Independent Inflammatory Responses
Koedel, U., Merbt, U. M., Schmidt, C., Angele, B., Popp, B., Wagner, H., Pfister, H.-W., & Kirschning, C. J. (2007) · The American Journal of Pathology · doi:10.2353/ajpath.2007.060821 · Cited by 78 · see citing works
Strömberg, A., Olsson, K., Dijksterhuis, J. P., Rullman, E., Schulte, G., & Gustafsson, T. (2016) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00236.2015 · Cited by 67 · see citing works
Fan, Q., He, W., Gayen, M., Benoit, M. R., Luo, X., Hu, X., & Yan, R. (2020) · The Journal of Neuroscience · doi:10.1523/jneurosci.1333-19.2019 · Cited by 58 · see citing works
Ischemia-induced Neuronal Cell Death Is Mediated by Chemokine Receptor CX3CR1
Wang, J., Gan, Y., Han, P., Yin, J., Liu, Q., Ghanian, S., Gao, F., Gong, G., & Tang, Z. (2018) · Scientific Reports · doi:10.1038/s41598-017-18774-0 · Cited by 58 · see citing works
Potential Impact of Prosthetic Biomaterials on the Periodontium: A Comprehensive Review
Alarcón-Sánchez, M. A., Heboyan, A., Fernandes, G. V. D. O., Castro-Alarcón, N., & Romero-Castro, N. S. (2023) · Molecules · doi:10.3390/molecules28031075 · Cited by 52 · see citing works
Zhao, T., Gao, S., Wang, X., Liu, J., Duan, Y., Yuan, Z., Sheng, J., Li, S., Wang, F., Yu, M., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0043399 · Cited by 48 · see citing works
Expression of fractalkine (CX3CL1) and its receptor, CX3CR1, in periodontal diseased tissue
Hosokawa, Y., Nakanishi, T., Yamaguchi, D., Nakae, H., & Matsuo, T. (2005) · Clinical and Experimental Immunology · doi:10.1111/j.1365-2249.2005.02675.x · Cited by 39 · see citing works
Bemiller, S. M., Maphis, N. M., Formica, S. V., Wilson, G. N., Miller, C. M., Xu, G., Kokiko-Cochran, O. N., Kim, K.-W., Jung, S., Cannon, J. L., et al. (2018) · Journal of Neuroinflammation · doi:10.1186/s12974-018-1310-6 · Cited by 24 · see citing works
Yilmaz, D., Gönüllü, E., Gürsoy, M., Könönen, E., & Gürsoy, U. K. (2021) · Journal of Periodontology · doi:10.1002/jper.20-0632 · Cited by 21 · see citing works
- Authors
- Bazan, J. F., Bacon, K. B., Hardiman, G., Wang, W., Soo, K., Rossi, D., Greaves, D. R., Zlotnik, A., & Schall, T. J.
- Venue
- Nature
- Published
- 1997-02
- Volume
- 385
- Issue
- 6617
- Pages
- 640-644
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1984115097
- Cited by
- 2,013
- References
- 1
- Citations by year
- 2026: 41 · 2025: 42 · 2024: 62 · 2023: 49 · 2022: 49 · 2021: 51 · 2020: 61 · 2019: 49 · 2018: 59 · 2017: 54 · 2016: 42 · 2015: 66 · 2014: 89 · 2013: 75 · 2012: 81
- FWCI
- 48.59
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Life Sciences › Immunology and Microbiology › Immunology › Inflammation biomarkers and pathways
- Keywords
- CX3C chemokines, chemokines, leukocyte migration, endothelial activation, T cell chemotaxis, monocyte adhesion, chemoattractant activity, leukocyte adhesion, tissue distribution, chromosomal localization
- MeSH terms
- Amino Acid Sequence, Cell Line, Chromosome Mapping, Cloning, Molecular, Humans, Hybrid Cells, Membrane Proteins, Molecular Sequence Data, Protein Binding, RNA, Messenger, Tissue Distribution, DNA, Complementary, Chemokines, Chemokines, CX3C, Chemokine CX3CL1
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 ›
Are you an author, or do you see a problem with this page? Request a review
