cx3c chemokines


Summary: Group of chemokines with the first two cysteines separated by three amino acids. CX3C chemokines are chemotactic for natural killer cells, monocytes, and activated T-cells.

Top Publications

  1. Bazan J, Bacon K, Hardiman G, Wang W, Soo K, Rossi D, et al. A new class of membrane-bound chemokine with a CX3C motif. Nature. 1997;385:640-4 pubmed
  2. Casarosa P, Waldhoer M, LiWang P, Vischer H, Kledal T, Timmerman H, et al. CC and CX3C chemokines differentially interact with the N terminus of the human cytomegalovirus-encoded US28 receptor. J Biol Chem. 2005;280:3275-85 pubmed
    ..located in the N terminus of US28 that differentially contribute to the high affinity binding of CC versus CX3C chemokines. Additionally, our results highlight the importance of secondary modifications occurring at US28, such as ..
  3. Stievano L, Piovan E, Amadori A. C and CX3C chemokines: cell sources and physiopathological implications. Crit Rev Immunol. 2004;24:205-28 pubmed
    Within the fascinating world of chemokines, C and CX3C chemokines have long been regarded as two minor components, even though they present unique features and show less redundancy than the other chemokine families...
  4. Lesnik P, Haskell C, Charo I. Decreased atherosclerosis in CX3CR1-/- mice reveals a role for fractalkine in atherogenesis. J Clin Invest. 2003;111:333-40 pubmed
    ..CX(3)CR1(-/-) mice have a significant reduction in macrophage recruitment to the vessel wall and decreased atherosclerotic lesion formation. Taken together, these data provide strong evidence that FK plays a key role in atherogenesis. ..
  5. Combadiere C, Potteaux S, Gao J, Esposito B, Casanova S, Lee E, et al. Decreased atherosclerotic lesion formation in CX3CR1/apolipoprotein E double knockout mice. Circulation. 2003;107:1009-16 pubmed
    ..The CX3CR1-CX3CL1 pathway seems to play a direct and critical role in monocyte recruitment and atherosclerotic lesion development in a mouse model of human atherosclerosis. ..
  6. Umehara H, Bloom E, Okazaki T, Domae N, Imai T. Fractalkine and vascular injury. Trends Immunol. 2001;22:602-7 pubmed
    ..Here, we propose a model in which fractalkine mediates vascular injury through the accumulation and activation of killer cells. ..
  7. Wilbanks A, Zondlo S, Murphy K, Mak S, Soler D, Langdon P, et al. Expression cloning of the STRL33/BONZO/TYMSTRligand reveals elements of CC, CXC, and CX3C chemokines. J Immunol. 2001;166:5145-54 pubmed
    ..Additionally, this chemokine might play a unique dual role of attracting activated lymphocyte subsets during inflammation as well as facilitating immune responses via cell-cell contact. ..
  8. Cook D, Chen S, Sullivan L, Manfra D, Wiekowski M, Prosser D, et al. Generation and analysis of mice lacking the chemokine fractalkine. Mol Cell Biol. 2001;21:3159-65 pubmed
    ..Similarly, the responses of fractalkine(-/-) mice to a variety of inflammatory stimuli were indistinguishable from those of wild-type mice. ..
  9. Pereira C, Middel J, Jansen G, Verhoef J, Nottet H. Enhanced expression of fractalkine in HIV-1 associated dementia. J Neuroimmunol. 2001;115:168-75 pubmed
    ..We propose that fractalkine produced during interactions between astrocytes and HIV-infected macrophages plays a role in HAD by regulating the trafficking of monocytic cells in the brain parenchyma. ..

More Information


  1. Imai T, Hieshima K, Haskell C, Baba M, Nagira M, Nishimura M, et al. Identification and molecular characterization of fractalkine receptor CX3CR1, which mediates both leukocyte migration and adhesion. Cell. 1997;91:521-30 pubmed
    ..Thus, fractalkine and CX3CR1 represent new types of leukocyte trafficking regulators, performing both adhesive and chemotactic functions. ..
  2. Becker Y. Respiratory syncytial virus(RSV)-induced allergy may be controlled by IL-4 and CX3C fractalkine antagonists and CpG ODN as adjuvant: hypothesis and implications for treatment. Virus Genes. 2006;33:253-64 pubmed
    ..It is also suggested that the less-pathogenic RSV strain Long may be a candidate for vaccine development after deletion of the FKN and superantigen domains from the G gene. ..
  3. Merendino R, Di Pasquale G, De Luca F, Di Pasquale L, Ferlazzo E, Martino G, et al. Involvement of fractalkine and macrophage inflammatory protein-1 alpha in moderate-severe depression. Mediators Inflamm. 2004;13:205-7 pubmed
    ..In conclusion, we describe a previously unknown involvement of FKN in the pathogenesis of MSD, suggesting that FKN may represent a target for a specific immune therapy of this disease. ..
  4. Minami M. [Cytokines and chemokines: mediators for intercellular communication in the brain]. Yakugaku Zasshi. 2001;121:875-85 pubmed
    ..They are potential targets for therapeutic intervention for neurodegenerative diseases. ..
  5. Pietrzyk M, Banas B, Wolf K, Rümmele P, Woenckhaus M, Hoffmann U, et al. Quantitative gene expression analysis of fractalkine using laser microdissection in biopsies from kidney allografts with acute rejection. Transplant Proc. 2004;36:2659-61 pubmed
    ..37 to 5.11] to 7.07 [1.19 to 73.49] (P < .01). Furthermore, there was a trend toward higher glomerular FKN expression among patients with more severe rejection. Our results suggest a role of FKN in acute renal allograft rejection. ..
  6. Boomker J, van Luyn M, The T, de Leij L, Harmsen M. US28 actions in HCMV infection: lessons from a versatile hijacker. Rev Med Virol. 2005;15:269-82 pubmed
    ..This review will elaborate on these aspects of US28 biology and discuss possible implications for HCMV infection. ..
  7. Boisvert W. Modulation of atherogenesis by chemokines. Trends Cardiovasc Med. 2004;14:161-5 pubmed
    ..Furthermore, based on present knowledge of the participation of these three chemokines and their receptors in monocyte/macrophage recruitment, a possible interactive role of these chemokines in atherogenesis is explored. ..
  8. Yoshikawa M, Nakajima T, Matsumoto K, Okada N, Tsukidate T, Iida M, et al. TNF-alpha and IL-4 regulate expression of fractalkine (CX3CL1) as a membrane-anchored proadhesive protein and soluble chemotactic peptide on human fibroblasts. FEBS Lett. 2004;561:105-10 pubmed
    ..These results suggest that TNF-alpha- and IL-4-stimulated fibroblasts may play an important role in accumulation of monocytes at inflammatory sites. ..
  9. Balabanian K, Foussat A, Dorfmuller P, Durand Gasselin I, Capel F, Bouchet Delbos L, et al. CX(3)C chemokine fractalkine in pulmonary arterial hypertension. Am J Respir Crit Care Med. 2002;165:1419-25 pubmed
    ..Fractalkine mRNA and protein product are expressed in pulmonary artery endothelial cells. We conclude that inflammatory mechanisms involving chemokine fractalkine and its receptor CX(3)CR1 may have a role in the natural history of PAH. ..
  10. Schafer A, Schulz C, Eigenthaler M, Fraccarollo D, Kobsar A, Gawaz M, et al. Novel role of the membrane-bound chemokine fractalkine in platelet activation and adhesion. Blood. 2004;103:407-12 pubmed
  11. Bolger W, Joshi A, Spear S, Nelson M, Govindaraj K. Gene expression analysis in sinonasal polyposis before and after oral corticosteroids: a preliminary investigation. Otolaryngol Head Neck Surg. 2007;137:27-33 pubmed
    ..Gene array techniques hold promise as a research method in sinonasal polyposis. The potential benefits, as well as the potential challenges, in using these research methods will be discussed. ..
  12. Hassoun P, Mouthon L, Barbera J, Eddahibi S, Flores S, Grimminger F, et al. Inflammation, growth factors, and pulmonary vascular remodeling. J Am Coll Cardiol. 2009;54:S10-9 pubmed publisher
  13. Johnson T, Teng M, Collins P, Graham B. Respiratory syncytial virus (RSV) G glycoprotein is not necessary for vaccine-enhanced disease induced by immunization with formalin-inactivated RSV. J Virol. 2004;78:6024-32 pubmed
  14. Barlic J, Zhang Y, Murphy P. Atherogenic lipids induce adhesion of human coronary artery smooth muscle cells to macrophages by up-regulating chemokine CX3CL1 on smooth muscle cells in a TNFalpha-NFkappaB-dependent manner. J Biol Chem. 2007;282:19167-76 pubmed
  15. Robinson L, Nataraj C, Thomas D, Cosby J, Griffiths R, Bautch V, et al. The chemokine CX3CL1 regulates NK cell activity in vivo. Cell Immunol. 2003;225:122-30 pubmed
    ..NK cell binding to activated endothelial monolayers was significantly inhibited by anti-CX(3)CR1 Ab or soluble CX(3)CL1 (p<0.001). These studies identify a critical role for CX(3)CL1 in modulating NK cell activity in vivo. ..
  16. Mizoue L, Bazan J, Johnson E, Handel T. Solution structure and dynamics of the CX3C chemokine domain of fractalkine and its interaction with an N-terminal fragment of CX3CR1. Biochemistry. 1999;38:1402-14 pubmed
    ..Together, these data provide a first glimpse of how fractalkine interacts with its receptor and should help guide mutagenesis studies to further elucidate the molecular details of binding and signaling through CX3CR1. ..
  17. Streblow D, Kreklywich C, Yin Q, De La Melena V, Corless C, Smith P, et al. Cytomegalovirus-mediated upregulation of chemokine expression correlates with the acceleration of chronic rejection in rat heart transplants. J Virol. 2003;77:2182-94 pubmed
    ..These results suggest that CMV-induced acceleration of TVS involves the increased graft vascular infiltration of inflammatory cells through enhanced chemokine expression. ..
  18. Fraile Ramos A, Kledal T, Pelchen Matthews A, Bowers K, Schwartz T, Marsh M. The human cytomegalovirus US28 protein is located in endocytic vesicles and undergoes constitutive endocytosis and recycling. Mol Biol Cell. 2001;12:1737-49 pubmed
    ..In addition, the distribution of US28 mainly on endosomal membranes may allow it to be incorporated into the viral envelope during HCMV assembly. ..
  19. Apolinario A, Majano P, Alvarez Pérez E, Saez A, Lozano C, Vargas J, et al. Increased expression of T cell chemokines and their receptors in chronic hepatitis C: relationship with the histological activity of liver disease. Am J Gastroenterol. 2002;97:2861-70 pubmed
    ..Intrahepatic chemokine signaling could play a key role regulating significant pathological events during chronic hepatitis C, opening new avenues for therapeutic interventions based on chemokine activities. ..
  20. Cercek M, Matsumoto M, Li H, Chyu K, Peter A, Shah P, et al. Autocrine role of vascular IL-15 in intimal thickening. Biochem Biophys Res Commun. 2006;339:618-23 pubmed
    ..These data suggest that endogenous IL-15 attenuated intimal thickening after arterial injury. The potential mechanism of action is suppression of CX3CR1 signaling. ..
  21. Sukkar M, Issa R, Xie S, Oltmanns U, Newton R, Chung K. Fractalkine/CX3CL1 production by human airway smooth muscle cells: induction by IFN-gamma and TNF-alpha and regulation by TGF-beta and corticosteroids. Am J Physiol Lung Cell Mol Physiol. 2004;287:L1230-40 pubmed
    ..In summary, FKN production by human ASMC in vitro is regulated by inflammatory and anti-inflammatory factors. ..
  22. Zeng Y, Jiang J, Huebener N, Wenkel J, Gaedicke G, Xiang R, et al. Fractalkine gene therapy for neuroblastoma is more effective in combination with targeted IL-2. Cancer Lett. 2005;228:187-93 pubmed
    ..In summary, we demonstrated for the first time that chemokine gene therapy is amplified by targeted IL-2 suggesting a combination of both strategies as an adjuvant therapy for neuroblastoma. ..
  23. Moatti D, Vele O, Nemerson Y. Induction of fractalkine by endothelial cells under shear stress. Blood Coagul Fibrinolysis. 2004;15:197 pubmed
  24. Boehme S, Lio F, Maciejewski Lenoir D, Bacon K, Conlon P. The chemokine fractalkine inhibits Fas-mediated cell death of brain microglia. J Immunol. 2000;165:397-403 pubmed
    ..These results, therefore, suggest that the interaction between fractalkine and CX3CR-1 may play an important role in promoting and preserving microglial cell survival in the CNS. ..
  25. Foussat A, Bouchet Delbos L, Berrebi D, Durand Gasselin I, Coulomb L Hermine A, Krzysiek R, et al. Deregulation of the expression of the fractalkine/fractalkine receptor complex in HIV-1-infected patients. Blood. 2001;98:1678-86 pubmed
    ..Thus, it may influence the equilibrium between depletion and renewal of the Th lymphocyte compartment. ..
  26. Papadopoulos E, Sassetti C, Saeki H, Yamada N, Kawamura T, Fitzhugh D, et al. Fractalkine, a CX3C chemokine, is expressed by dendritic cells and is up-regulated upon dendritic cell maturation. Eur J Immunol. 1999;29:2551-9 pubmed
  27. Echigo T, Hasegawa M, Shimada Y, Takehara K, Sato S. Expression of fractalkine and its receptor, CX3CR1, in atopic dermatitis: possible contribution to skin inflammation. J Allergy Clin Immunol. 2004;113:940-8 pubmed
    ..These results suggest that through functions in both membrane-bound and soluble forms, FKN plays an important role in the trafficking of CX(3)CR1(+) leukocytes during the inflammation caused by AD. ..
  28. Yoneda O, Imai T, Goda S, Inoue H, Yamauchi A, Okazaki T, et al. Fractalkine-mediated endothelial cell injury by NK cells. J Immunol. 2000;164:4055-62 pubmed
    ..Our results suggest that fractalkine plays an important role not only in the binding of NK cells to endothelial cells, but also in NK cell-mediated endothelium damage, which may result in vascular injury. ..
  29. Umehara H, Goda S, Imai T, Nagano Y, Minami Y, Tanaka Y, et al. Fractalkine, a CX3C-chemokine, functions predominantly as an adhesion molecule in monocytic cell line THP-1. Immunol Cell Biol. 2001;79:298-302 pubmed
    ..These results indicate that fractalkine may function as an adhesion molecule between monocytes and endothelial cells rather than as a chemotactic factor. ..
  30. Volin M, Huynh N, Klosowska K, Chong K, Woods J. Fractalkine is a novel chemoattractant for rheumatoid arthritis fibroblast-like synoviocyte signaling through MAP kinases and Akt. Arthritis Rheum. 2007;56:2512-22 pubmed
    ..These findings indicate a novel role of FKN in regulating RA FLS cytoskeletal structure and migration. FKN specifically induces RA FLS phosphorylation of the MAP kinases JNK and ERK-1/2, as well as full activation of Akt. ..
  31. Chapman G, Moores K, Harrison D, Campbell C, Stewart B, Strijbos P. Fractalkine cleavage from neuronal membranes represents an acute event in the inflammatory response to excitotoxic brain damage. J Neurosci. 2000;20:RC87 pubmed
  32. Casarosa P, Bakker R, Verzijl D, Navis M, Timmerman H, Leurs R, et al. Constitutive signaling of the human cytomegalovirus-encoded chemokine receptor US28. J Biol Chem. 2001;276:1133-7 pubmed
  33. Robinson L, Nataraj C, Thomas D, Howell D, Griffiths R, Bautch V, et al. A role for fractalkine and its receptor (CX3CR1) in cardiac allograft rejection. J Immunol. 2000;165:6067-72 pubmed
    ..0008). These studies identify a critical role for FKN in the pathogenesis of acute rejection and suggest that FKN may be a useful therapeutic target in rejection. ..
  34. Bolovan Fritts C, Trout R, Spector S. Human cytomegalovirus-specific CD4+-T-cell cytokine response induces fractalkine in endothelial cells. J Virol. 2004;78:13173-81 pubmed
  35. Ancuta P, Wang J, Gabuzda D. CD16+ monocytes produce IL-6, CCL2, and matrix metalloproteinase-9 upon interaction with CX3CL1-expressing endothelial cells. J Leukoc Biol. 2006;80:1156-64 pubmed
  36. Ancuta P, Moses A, Gabuzda D. Transendothelial migration of CD16+ monocytes in response to fractalkine under constitutive and inflammatory conditions. Immunobiology. 2004;209:11-20 pubmed
  37. Obara H, Nagasaki K, Hsieh C, Ogura Y, Esquivel C, Martinez O, et al. IFN-gamma, produced by NK cells that infiltrate liver allografts early after transplantation, links the innate and adaptive immune responses. Am J Transplant. 2005;5:2094-103 pubmed
    ..Furthermore, graft survival was significantly prolonged. These data suggest that IFN-gamma-producing NK cells are an important link between the innate and adaptive immune responses early after transplantation. ..
  38. Schulz C, Schafer A, Stolla M, Kerstan S, Lorenz M, von Brühl M, et al. Chemokine fractalkine mediates leukocyte recruitment to inflammatory endothelial cells in flowing whole blood: a critical role for P-selectin expressed on activated platelets. Circulation. 2007;116:764-73 pubmed
  39. Tam F, Sanders J, George A, Hammad T, Miller C, Dougan T, et al. Urinary monocyte chemoattractant protein-1 (MCP-1) is a marker of active renal vasculitis. Nephrol Dial Transplant. 2004;19:2761-8 pubmed
    ..05). This study shows that measurement of urinary MCP-1, but not fractalkine, is a useful non-invasive technique for the assessment of renal involvement and monitoring the response to therapy in ANCA-associated vasculitis. ..
  40. Ji J, He B, Dheen S, Tay S. Interactions of chemokines and chemokine receptors mediate the migration of mesenchymal stem cells to the impaired site in the brain after hypoglossal nerve injury. Stem Cells. 2004;22:415-27 pubmed
    ..This study provides an important insight into the understanding of the mechanisms governing the trafficking of transplanted rMSCs and also significantly expands the potential role of MSCs in cell therapy for brain injuries and diseases. ..
  41. Ahn S, Cho C, Park K, Lee H, Lee S, Park S, et al. Tumor necrosis factor-alpha induces fractalkine expression preferentially in arterial endothelial cells and mithramycin A suppresses TNF-alpha-induced fractalkine expression. Am J Pathol. 2004;164:1663-72 pubmed
    ..NF-kappaB and Sp1 inhibitors such as mithramycin A may provide a pharmacological approach to suppressing these processes. ..
  42. Hatakeyama M, Imaizumi T, Tamo W, Yamashita K, Yoshida H, Fukuda I, et al. Heparin inhibits IFN-gamma-induced fractalkine/CX3CL1 expression in human endothelial cells. Inflammation. 2004;28:7-13 pubmed
    ..Heparin may play a regulatory role in inflammatory and immune responses by modulating the interaction between leukocytes and the vascular endothelium. ..
  43. Efsen E, Grappone C, Defranco R, Milani S, Romanelli R, Bonacchi A, et al. Up-regulated expression of fractalkine and its receptor CX3CR1 during liver injury in humans. J Hepatol. 2002;37:39-47 pubmed
    ..This study shows that the fractalkine system is up-regulated during liver damage, and suggests that fractalkine may play a role in the recruitment and adhesion of inflammatory cells and in the biology of liver epithelial cells. ..
  44. Houshmand P, Zlotnik A. Therapeutic applications in the chemokine superfamily. Curr Opin Chem Biol. 2003;7:457-60 pubmed
    ..Here we review some of the most compelling opportunities for drug development in this area. ..
  45. Gu X, Tang X, Gu S, Yang S, Zhou P, Tan J. [Expression of fractalkine and its receptor in acute cardiac allografts rejection]. Zhonghua Wai Ke Za Zhi. 2003;41:139-42 pubmed
    ..It may be one of the important mechanisms of CsA to intervene the acute rejection by inhibiting the activation of the FKN-CX3CR1 pathway. ..
  46. Fahy O, Coates N, McColl S. Inhibition of cytokine-induced fractalkine production by bacterial invasion of human-dermal fibroblasts. Lab Invest. 2003;83:721-30 pubmed
    ..In addition, our data indicate that bacterial invasion of dermal fibroblasts actively modulates FKN expression. ..
  47. Carter D, Dick A. CD200 maintains microglial potential to migrate in adult human retinal explant model. Curr Eye Res. 2004;28:427-36 pubmed
    ..Although MG do not classically activate following LPS/IFNgamma stimulation, their migration is sustained via CD200R stimulation maintaining their potential to migrate in response to injury. ..
  48. Fraticelli P, Sironi M, Bianchi G, D Ambrosio D, Albanesi C, Stoppacciaro A, et al. Fractalkine (CX3CL1) as an amplification circuit of polarized Th1 responses. J Clin Invest. 2001;107:1173-81 pubmed
    ..These results indicate that regulated expression of FKN in ECs participates in an amplification circuit of polarized type I responses. ..
  49. Ruth J, Volin M, Haines G, Woodruff D, Katschke K, Woods J, et al. Fractalkine, a novel chemokine in rheumatoid arthritis and in rat adjuvant-induced arthritis. Arthritis Rheum. 2001;44:1568-81 pubmed
    ..These results indicate that Fkn and its receptor are both expressed in RA and in rat AIA, and that sFkn is up-regulated in RA SF. Furthermore, our data suggest a new role for Fkn in monocyte chemotaxis in the inflamed RA joint. ..
  50. Tang L, Hu P, Hu H, Ren H. [Experimental gene therapy mediated by fractalkine (FK) for murine liver cancer]. Zhonghua Gan Zang Bing Za Zhi. 2005;13:675-7 pubmed
    ..The level of CD4+ and CD8+ T cells had obviously increased in MM45T.Li-FK compared to the controls (P < 0.01). Transfection with chemokine FK gene can induce anti-hepatocellular carcinoma active immune response. ..
  51. Xu Q, Wang S, Jiang X, Zhao Y, Gao M, Zhang Y, et al. Hypoxia-induced astrocytes promote the migration of neural progenitor cells via vascular endothelial factor, stem cell factor, stromal-derived factor-1alpha and monocyte chemoattractant protein-1 upregulation in vitro. Clin Exp Pharmacol Physiol. 2007;34:624-31 pubmed
    ..Given that astrocytes were activated to all hypoxia-ischaemia diseases, these results indicate an important role for astrocytes in directing NPC replacement therapy in the central nervous system. ..
  52. Zujovic V, Taupin V. Use of cocultured cell systems to elucidate chemokine-dependent neuronal/microglial interactions: control of microglial activation. Methods. 2003;29:345-50 pubmed
    ..Using these in vitro cocultured systems, we have investigated the role of a soluble and/or cell-associated chemokine, such as fractalkine, in order to obtain insights into the role of glia-neuron interactions in cerebral inflammation. ..
  53. Silverman M, Zamora D, Pan Y, Texeira P, Baek S, Planck S, et al. Constitutive and inflammatory mediator-regulated fractalkine expression in human ocular tissues and cultured cells. Invest Ophthalmol Vis Sci. 2003;44:1608-15 pubmed
    ..Inflammatory mediator modulation of ocular FKN expression suggests that this adhesive chemokine may play important roles in regulating leukocyte efflux in inflammatory eye diseases, such as anterior uveitis and retinochoroiditis. ..