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Gene Review

CX3CL1  -  chemokine (C-X3-C motif) ligand 1

Homo sapiens

Synonyms: A-152E5.2, ABCD-3, C-X3-C motif chemokine 1, C3Xkine, CX3C membrane-anchored chemokine, ...
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Disease relevance of CX3CL1


High impact information on CX3CL1


Chemical compound and disease context of CX3CL1

  • The effects of AS-6 on TNF-alpha-stimulated VCAM-1 and CX3CL1 expression were abolished in cells transfected with an adenovirus expressing dominant-negative PPARgamma and in cells treated with a PPARgamma specific inhibitor, GW9662, confirming again that the anti-inflammatory effect of AS-6 was PPARgamma-dependent [8].
  • Alterations in the expression of the chemokine, fractalkine (CX3CL1), were examined in the urinary bladder after cyclophosphamide (CYP)-induced cystitis of varying duration: acute (4 h or 48 h), or chronic (10 day) [9].
  • Alpha-lipoic acid inhibits fractalkine expression and prevents neointimal hyperplasia after balloon injury in rat carotid artery [10].
  • Moreover, FKN significantly reduced neuronal NMDA-induced apoptosis, which was pertussis toxin insensitive and abolished in presence of PD98059 and LY294002 [11].
  • Application of FKN triggered a 53% reduction of the NMDA-induced neuronal calcium influx, which was insensitive to pertussis toxin and LY294002 an inhibitor of Akt pathway, but abolished by PD98059, an ERK1/2 pathway inhibitor [11].

Biological context of CX3CL1


Anatomical context of CX3CL1

  • Using human pancreatic islets as an in vitro model of peripheral tissue, we showed that islet supernatants released factors able to attract BM-MSCs in vitro, and this attraction was principally mediated by CX3CL1 and CXCL12 [17].
  • The membrane-anchored form of CX3CL1 has been proposed as a novel adhesion protein for leukocytes [13].
  • Compatible with this hypothesis, stimulation of monocytes with MCP-1 significantly increased their adhesion to immobilized CX3CL1, under both static and physiological flow conditions [13].
  • METHODS: Using flow cytometry, immunohistochemistry, and reverse transcription-polymerase chain reaction, we analyzed CX3CR1 expression by peripheral blood and synovial T cells, and CX3CL1 expression in synovium from patients with RA [18].
  • Endometrial cell-conditioned media also stimulated trophoblast migration; this was attenuated by neutralizing antibodies to CX3CL1 and CCL4 [19].

Associations of CX3CL1 with chemical compounds


Physical interactions of CX3CL1

  • In steady state experiments, all three CX3CR1 isoforms bound CX3CL1 with similar affinity [25].
  • Fractalkine (CX3CL1) is a transmembrane molecule with a CX3C chemokine domain attached to an extracellular mucin stalk which can induce both adhesion and migration of leucocytes [26].

Co-localisations of CX3CL1


Regulatory relationships of CX3CL1

  • Combined stimulation with IFN-gamma and TNF-alpha induced FKN mRNA and protein expression in a time- and concentration-dependent manner [23].
  • RESULTS: Flow cytometric analysis of fractalkine-expressing T cell subsets revealed a low proportion of fractalkine-expressing CD4+ and CD8+ T cells in both RA patients and controls [28].
  • There is a positive correlation between the number of fractalkine-expressing cells and the number of CX3CR1-positive cells in human atherosclerotic plaques (r=0.70, n=15 plaques) [29].
  • Moreover, the membrane form of fractalkine expressed on ECV304 cells reduced MCP-1 mediated chemotaxis of THP-1 cells [30].
  • Furthermore, we observed that s-FKN also inhibits the activity of a major matrix metalloproteinase (MMP), namely MMP-2 [15].

Other interactions of CX3CL1

  • These results demonstrate that FKN preferentially mediates arrest and migration of CD16+ monocytes and suggest that recruitment of this proinflammatory monocyte subset to vessel walls via the CX3CR1-FKN pathway may contribute to vascular and tissue injury during pathological conditions [31].
  • Inhibition of ADAM10-mediated CX3CL1 shedding not only increased adhesive properties of CX3CL1-ECV-304 cells but also prevented de-adhesion of bound THP-1 cells [12].
  • High levels of MDC, TARC, and fractalkine mRNA expression are seen in some, but not all, human arteries with advanced atherosclerotic lesions [32].
  • Unlike other human chemokines, the chemokine domain of fractalkine has three amino acids between two conserved cysteines, referred to as the CX3C motif [33].
  • In this study, we address the question of the cross-talk between two chemokines that are cosecreted during inflammation, namely monocyte chemoattractant protein-1 (MCP-1) and soluble fractalkine (s-FKN), toward monocyte migration [15].

Analytical, diagnostic and therapeutic context of CX3CL1


  1. Major reduction of atherosclerosis in fractalkine (CX3CL1)-deficient mice is at the brachiocephalic artery, not the aortic root. Teupser, D., Pavlides, S., Tan, M., Gutierrez-Ramos, J.C., Kolbeck, R., Breslow, J.L. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  2. The chemokine fractalkine in patients with severe traumatic brain injury and a mouse model of closed head injury. Rancan, M., Bye, N., Otto, V.I., Trentz, O., Kossmann, T., Frentzel, S., Morganti-Kossmann, M.C. J. Cereb. Blood Flow Metab. (2004) [Pubmed]
  3. Up regulated expression of fractalkine/CX3CL1 and CX3CR1 in patients with systemic sclerosis. Hasegawa, M., Sato, S., Echigo, T., Hamaguchi, Y., Yasui, M., Takehara, K. Ann. Rheum. Dis. (2005) [Pubmed]
  4. Fractalkine (CX3CL1) and brain inflammation: Implications for HIV-1-associated dementia. Cotter, R., Williams, C., Ryan, L., Erichsen, D., Lopez, A., Peng, H., Zheng, J. J. Neurovirol. (2002) [Pubmed]
  5. Characterization of fractalkine (CX3CL1) and CX3CR1 in human coronary arteries with native atherosclerosis, diabetes mellitus, and transplant vascular disease. Wong, B.W., Wong, D., McManus, B.M. Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology. (2002) [Pubmed]
  6. Identification and molecular characterization of fractalkine receptor CX3CR1, which mediates both leukocyte migration and adhesion. Imai, T., Hieshima, K., Haskell, C., Baba, M., Nagira, M., Nishimura, M., Kakizaki, M., Takagi, S., Nomiyama, H., Schall, T.J., Yoshie, O. Cell (1997) [Pubmed]
  7. Neurotactin, a membrane-anchored chemokine upregulated in brain inflammation. Pan, Y., Lloyd, C., Zhou, H., Dolich, S., Deeds, J., Gonzalo, J.A., Vath, J., Gosselin, M., Ma, J., Dussault, B., Woolf, E., Alperin, G., Culpepper, J., Gutierrez-Ramos, J.C., Gearing, D. Nature (1997) [Pubmed]
  8. The ascochlorin derivative, AS-6, inhibits TNF-alpha-induced adhesion molecule and chemokine expression in rat vascular smooth muscle cells. Park, K.G., Lee, K.M., Chang, Y.C., Magae, J., Ando, K., Kim, K.B., Kim, Y.N., Kim, H.S., Park, J.Y., Lee, K.U., Lee, I.K. Life Sci. (2006) [Pubmed]
  9. Expression of fractalkine and fractalkine receptor in urinary bladder after cyclophosphamide (CYP)-induced cystitis. Yuridullah, R., Corrow, K.A., Malley, S.E., Vizzard, M.A. Autonomic neuroscience : basic & clinical. (2006) [Pubmed]
  10. Alpha-lipoic acid inhibits fractalkine expression and prevents neointimal hyperplasia after balloon injury in rat carotid artery. Lee, K.M., Park, K.G., Kim, Y.D., Lee, H.J., Kim, H.T., Cho, W.H., Kim, H.S., Han, S.W., Koh, G.Y., Park, J.Y., Lee, K.U., Kim, J.G., Lee, I.K. Atherosclerosis (2006) [Pubmed]
  11. Fractalkine reduces N-methyl-d-aspartate-induced calcium flux and apoptosis in human neurons through extracellular signal-regulated kinase activation. Deiva, K., Geeraerts, T., Salim, H., Leclerc, P., Héry, C., Hugel, B., Freyssinet, J.M., Tardieu, M. Eur. J. Neurosci. (2004) [Pubmed]
  12. The disintegrin-like metalloproteinase ADAM10 is involved in constitutive cleavage of CX3CL1 (fractalkine) and regulates CX3CL1-mediated cell-cell adhesion. Hundhausen, C., Misztela, D., Berkhout, T.A., Broadway, N., Saftig, P., Reiss, K., Hartmann, D., Fahrenholz, F., Postina, R., Matthews, V., Kallen, K.J., Rose-John, S., Ludwig, A. Blood (2003) [Pubmed]
  13. The CC chemokine MCP-1 stimulates surface expression of CX3CR1 and enhances the adhesion of monocytes to fractalkine/CX3CL1 via p38 MAPK. Green, S.R., Han, K.H., Chen, Y., Almazan, F., Charo, I.F., Miller, Y.I., Quehenberger, O. J. Immunol. (2006) [Pubmed]
  14. Coexpression of fractalkine and its receptor in normal human endometrium and in endometrium from users of progestin-only contraception supports a role for fractalkine in leukocyte recruitment and endometrial remodeling. Hannan, N.J., Jones, R.L., Critchley, H.O., Kovacs, G.J., Rogers, P.A., Affandi, B., Salamonsen, L.A. J. Clin. Endocrinol. Metab. (2004) [Pubmed]
  15. Soluble fractalkine prevents monocyte chemoattractant protein-1-induced monocyte migration via inhibition of stress-activated protein kinase 2/p38 and matrix metalloproteinase activities. Vitale, S., Schmid-Alliana, A., Breuil, V., Pomeranz, M., Millet, M.A., Rossi, B., Schmid-Antomarchi, H. J. Immunol. (2004) [Pubmed]
  16. Viral macrophage inflammatory protein-II and fractalkine (CX3CL1) chimeras identify molecular determinants of affinity, efficacy, and selectivity at CX3CR1. Davis, C.N., Zujovic, V., Harrison, J.K. Mol. Pharmacol. (2004) [Pubmed]
  17. Bone marrow mesenchymal stem cells express a restricted set of functionally active chemokine receptors capable of promoting migration to pancreatic islets. Sordi, V., Malosio, M.L., Marchesi, F., Mercalli, A., Melzi, R., Giordano, T., Belmonte, N., Ferrari, G., Leone, B.E., Bertuzzi, F., Zerbini, G., Allavena, P., Bonifacio, E., Piemonti, L. Blood (2005) [Pubmed]
  18. Migration of CX3CR1-positive T cells producing type 1 cytokines and cytotoxic molecules into the synovium of patients with rheumatoid arthritis. Nanki, T., Imai, T., Nagasaka, K., Urasaki, Y., Nonomura, Y., Taniguchi, K., Hayashida, K., Hasegawa, J., Yoshie, O., Miyasaka, N. Arthritis Rheum. (2002) [Pubmed]
  19. The Chemokines, CX3CL1, CCL14, and CCL4, Promote Human Trophoblast Migration at the Feto-Maternal Interface. Hannan, N.J., Jones, R.L., White, C.A., Salamonsen, L.A. Biol. Reprod. (2006) [Pubmed]
  20. Tumor necrosis factor-alpha-converting enzyme (ADAM17) mediates the cleavage and shedding of fractalkine (CX3CL1). Garton, K.J., Gough, P.J., Blobel, C.P., Murphy, G., Greaves, D.R., Dempsey, P.J., Raines, E.W. J. Biol. Chem. (2001) [Pubmed]
  21. Fractalkine/CX3CL1 production by human aortic smooth muscle cells impairs monocyte procoagulant and inflammatory responses. Ollivier, V., Faure, S., Tarantino, N., Chollet-Martin, S., Deterre, P., Combadière, C., de Prost, D. Cytokine (2003) [Pubmed]
  22. Fractalkine is expressed by smooth muscle cells in response to IFN-gamma and TNF-alpha and is modulated by metalloproteinase activity. Ludwig, A., Berkhout, T., Moores, K., Groot, P., Chapman, G. J. Immunol. (2002) [Pubmed]
  23. Fractalkine/CX3CL1 production by human airway smooth muscle cells: induction by IFN-gamma and TNF-alpha and regulation by TGF-beta and corticosteroids. Sukkar, M.B., Issa, R., Xie, S., Oltmanns, U., Newton, R., Chung, K.F. Am. J. Physiol. Lung Cell Mol. Physiol. (2004) [Pubmed]
  24. Fractalkine mediates T cell-dependent proliferation of synovial fibroblasts in rheumatoid arthritis. Sawai, H., Park, Y.W., He, X., Goronzy, J.J., Weyand, C.M. Arthritis Rheum. (2007) [Pubmed]
  25. Two novel fully functional isoforms of CX3CR1 are potent HIV coreceptors. Garin, A., Tarantino, N., Faure, S., Daoudi, M., Lécureuil, C., Bourdais, A., Debré, P., Deterre, P., Combadiere, C. J. Immunol. (2003) [Pubmed]
  26. Fractalkine expression on human renal tubular epithelial cells: potential role in mononuclear cell adhesion. Chakravorty, S.J., Cockwell, P., Girdlestone, J., Brooks, C.J., Savage, C.O. Clin. Exp. Immunol. (2002) [Pubmed]
  27. Expression of Fractalkine, CX3CR1, and Vascular Endothelial Growth Factor in Human Chronic Renal Allograft Rejection. Cao, G., Lu, Y., Gao, R., Xin, Y., Teng, D., Wang, J., Li, Y. Transplant. Proc. (2006) [Pubmed]
  28. Proinflammatory role of fractalkine (CX3CL1) in rheumatoid arthritis. Blaschke, S., Koziolek, M., Schwarz, A., Benöhr, P., Middel, P., Schwarz, G., Hummel, K.M., Müller, G.A. J. Rheumatol. (2003) [Pubmed]
  29. Smooth muscle cells in human atherosclerotic plaques express the fractalkine receptor CX3CR1 and undergo chemotaxis to the CX3C chemokine fractalkine (CX3CL1). Lucas, A.D., Bursill, C., Guzik, T.J., Sadowski, J., Channon, K.M., Greaves, D.R. Circulation (2003) [Pubmed]
  30. Fractalkine, a CX3C-chemokine, functions predominantly as an adhesion molecule in monocytic cell line THP-1. Umehara, H., Goda, S., Imai, T., Nagano, Y., Minami, Y., Tanaka, Y., Okazaki, T., Bloom, E.T., Domae, N. Immunol. Cell Biol. (2001) [Pubmed]
  31. Fractalkine preferentially mediates arrest and migration of CD16+ monocytes. Ancuta, P., Rao, R., Moses, A., Mehle, A., Shaw, S.K., Luscinskas, F.W., Gabuzda, D. J. Exp. Med. (2003) [Pubmed]
  32. Linked chromosome 16q13 chemokines, macrophage-derived chemokine, fractalkine, and thymus- and activation-regulated chemokine, are expressed in human atherosclerotic lesions. Greaves, D.R., Häkkinen, T., Lucas, A.D., Liddiard, K., Jones, E., Quinn, C.M., Senaratne, J., Green, F.R., Tyson, K., Boyle, J., Shanahan, C., Weissberg, P.L., Gordon, S., Ylä-Hertualla, S. Arterioscler. Thromb. Vasc. Biol. (2001) [Pubmed]
  33. Identification of CX3CR1. A chemotactic receptor for the human CX3C chemokine fractalkine and a fusion coreceptor for HIV-1. Combadiere, C., Salzwedel, K., Smith, E.D., Tiffany, H.L., Berger, E.A., Murphy, P.M. J. Biol. Chem. (1998) [Pubmed]
  34. Expression of fractalkine in the Fallopian tube and of CX3CR1 in sperm. Zhang, Q., Shimoya, K., Temma, K., Kimura, T., Tsujie, T., Shioji, M., Wasada, K., Fukui, O., Hayashi, S., Kanagawa, T., Kanzaki, T., Koyama, M., Murata, Y. Hum. Reprod. (2004) [Pubmed]
  35. Fractalkine in vascular biology: from basic research to clinical disease. Umehara, H., Bloom, E.T., Okazaki, T., Nagano, Y., Yoshie, O., Imai, T. Arterioscler. Thromb. Vasc. Biol. (2004) [Pubmed]
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