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Gene Review

Ccl3  -  chemokine (C-C motif) ligand 3

Mus musculus

Synonyms: AI323804, C-C motif chemokine 3, CCL3, G0S19-1, Heparin-binding chemotaxis protein, ...
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Disease relevance of Ccl3

  • In this review, different aspects of human and mouse MIP-1alpha and MIP-1beta are discussed, including their protein and gene structures, their regulated production, their receptor usage and biological activities and their role in several pathologies including HIV-1 infection [1].
  • Nonetheless, despite this possible compensation, our studies show the importance of MIP-1alpha in demyelination in the CNS and highlight its effect, particularly on cellular recruitment and cytokine regulation [2].
  • Superoxide dismutase 1 overexpression reduces MCP-1 and MIP-1 alpha expression after transient focal cerebral ischemia [3].
  • Increased expression of MIP-1 alpha and MIP-1 beta mRNAs in the brain correlates spatially and temporally with the spongiform neurodegeneration induced by a murine oncornavirus [4].
  • Macrophage inflammatory protein 1alpha (MIP-1alpha)/CCL3 prevents the development of eosinophilic pneumonia (EP) driven by a nonprotective T2-type immunity during infection with a highly virulent strain of Cryptococcus neoformans [5].

Psychiatry related information on Ccl3


High impact information on Ccl3


Chemical compound and disease context of Ccl3


Biological context of Ccl3


Anatomical context of Ccl3

  • In vivo trafficking assays demonstrated a requirement for IFN-alpha/betaR signaling for leukocyte localization in, and delivery of MIP-1alpha-producing macrophages to, the liver [19].
  • IFN-alpha/beta was required for NK cell accumulation during infection, and MIP-1alpha was required for NK cell accumulation in response to administered rIFN-alpha [19].
  • RESULTS: Toxin A induced in all mice a significant (P < 0.05) increase in ileal fluid accumulation, epithelial damage, and neutrophil infiltration, with all parameters being significantly (P < 0.01) lower in CCR1-/- and MIP-1alpha-/- mice [20].
  • Donor-derived MIP-1 alpha may play a role in allogeneic-induced IPS by limiting aggressive expansion of CD4(+) and CD8(+) T cells [21].
  • In addition, this study further attests to the alternative mechanisms of action used by MIP-1alpha in inhibition of hematopoietic progenitor-cell proliferation and regulation of leukocyte migration [22].

Associations of Ccl3 with chemical compounds


Physical interactions of Ccl3


Regulatory relationships of Ccl3


Other interactions of Ccl3

  • MIP-1 alpha and IL-1 beta mRNA were found only in LC, but not in other epidermal cells [15].
  • When PMN from CLP rodents were incubated in vitro with either MCP-1 or MIP-1 alpha, release of IL-6 was also shown [32].
  • RANTES induces rapid expression of transcripts for the CXC chemokines KC and macrophage inflammatory protein (MIP)-2, the CC chemokines MIP-1beta and MIP-1alpha, and the cytokines TNF-alpha and IL-6 [33].
  • The culture supernatant of these cells exerted the biologic activity of IL-10, showing inhibition of TNFalpha, MIP-1alpha, and MIP-1beta production by macrophages [34].
  • To the contrary, during the late phase of infection, an exaggerated Ag-specific IFN-gamma response was evident in CCR5-/- and MIP-1 alpha-/- mice, and this correlated with an enhanced control of parasite replication [35].

Analytical, diagnostic and therapeutic context of Ccl3


  1. Macrophage inflammatory protein-1. Menten, P., Wuyts, A., Van Damme, J. Cytokine Growth Factor Rev. (2002) [Pubmed]
  2. Absence of macrophage-inflammatory protein-1alpha delays central nervous system demyelination in the presence of an intact blood-brain barrier. McMahon, E.J., Cook, D.N., Suzuki, K., Matsushima, G.K. J. Immunol. (2001) [Pubmed]
  3. Superoxide dismutase 1 overexpression reduces MCP-1 and MIP-1 alpha expression after transient focal cerebral ischemia. Nishi, T., Maier, C.M., Hayashi, T., Saito, A., Chan, P.H. J. Cereb. Blood Flow Metab. (2005) [Pubmed]
  4. Increased expression of MIP-1 alpha and MIP-1 beta mRNAs in the brain correlates spatially and temporally with the spongiform neurodegeneration induced by a murine oncornavirus. Askovic, S., Favara, C., McAtee, F.J., Portis, J.L. J. Virol. (2001) [Pubmed]
  5. Regulatory effects of macrophage inflammatory protein 1alpha/CCL3 on the development of immunity to Cryptococcus neoformans depend on expression of early inflammatory cytokines. Olszewski, M.A., Huffnagle, G.B., Traynor, T.R., McDonald, R.A., Cook, D.N., Toews, G.B. Infect. Immun. (2001) [Pubmed]
  6. A proinflammatory chemokine, CCL3, sensitizes the heat- and capsaicin-gated ion channel TRPV1. Zhang, N., Inan, S., Inan, S., Cowan, A., Sun, R., Wang, J.M., Rogers, T.J., Caterina, M., Oppenheim, J.J. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  7. Identification and characterization of an inhibitor of haemopoietic stem cell proliferation. Graham, G.J., Wright, E.G., Hewick, R., Wolpe, S.D., Wilkie, N.M., Donaldson, D., Lorimore, S., Pragnell, I.B. Nature (1990) [Pubmed]
  8. Requirement of MIP-1 alpha for an inflammatory response to viral infection. Cook, D.N., Beck, M.A., Coffman, T.M., Kirby, S.L., Sheridan, J.F., Pragnell, I.B., Smithies, O. Science (1995) [Pubmed]
  9. A key role for ICAM-1 in generating effector cells mediating inflammatory responses. Camacho, S.A., Heath, W.R., Carbone, F.R., Sarvetnick, N., LeBon, A., Karlsson, L., Peterson, P.A., Webb, S.R. Nat. Immunol. (2001) [Pubmed]
  10. Two chemotactic factors, C5a and MIP-1alpha, dramatically alter the mortality from zymosan-induced multiple organ dysfunction syndrome (MODS): C5a contributes to MODS while MIP-1alpha has a protective role. Miller, C.G., Cook, D.N., Kotwal, G.J. Mol. Immunol. (1996) [Pubmed]
  11. Thalidomide upregulates macrophage inflammatory protein-1alpha in a herpes simplex virus-induced Behçet's disease-like animal model. Lee, E.S., Kim, Y.A., Kwon, H.J., Bang, D., Lee, S., Sohn, S. Arch. Dermatol. Res. (2004) [Pubmed]
  12. Macrophage inflammatory protein-1alpha as a costimulatory signal for mast cell-mediated immediate hypersensitivity reactions. Miyazaki, D., Nakamura, T., Toda, M., Cheung-Chau, K.W., Richardson, R.M., Ono, S.J. J. Clin. Invest. (2005) [Pubmed]
  13. Alterations of ambient oxygen tension modulate the expression of tumor necrosis factor and macrophage inflammatory protein-1 alpha from murine alveolar macrophages. VanOtteren, G.M., Standiford, T.J., Kunkel, S.L., Danforth, J.M., Strieter, R.M. Am. J. Respir. Cell Mol. Biol. (1995) [Pubmed]
  14. Perturbation of chemokine networks by gene deletion alters the reinforcing actions of ethanol. Blednov, Y.A., Bergeson, S.E., Walker, D., Ferreira, V.M., Kuziel, W.A., Harris, R.A. Behav. Brain Res. (2005) [Pubmed]
  15. Cytokine gene expression in murine epidermal cell suspensions: interleukin 1 beta and macrophage inflammatory protein 1 alpha are selectively expressed in Langerhans cells but are differentially regulated in culture. Heufler, C., Topar, G., Koch, F., Trockenbacher, B., Kämpgen, E., Romani, N., Schuler, G. J. Exp. Med. (1992) [Pubmed]
  16. Molecular cloning and characterization of a cDNA, CHEMR1, encoding a chemokine receptor with a homology to the human C-C chemokine receptor, CCR-4. Youn, B.S., Kim, S.H., Lyu, M.S., Kozak, C.A., Taub, D.D., Kwon, B.S. Blood (1997) [Pubmed]
  17. The tryptophan catabolite picolinic acid selectively induces the chemokines macrophage inflammatory protein-1 alpha and -1 beta in macrophages. Bosco, M.C., Rapisarda, A., Massazza, S., Melillo, G., Young, H., Varesio, L. J. Immunol. (2000) [Pubmed]
  18. Wound healing in MIP-1alpha(-/-) and MCP-1(-/-) mice. Low, Q.E., Drugea, I.A., Duffner, L.A., Quinn, D.G., Cook, D.N., Rollins, B.J., Kovacs, E.J., DiPietro, L.A. Am. J. Pathol. (2001) [Pubmed]
  19. Type I interferons regulate inflammatory cell trafficking and macrophage inflammatory protein 1alpha delivery to the liver. Salazar-Mather, T.P., Lewis, C.A., Biron, C.A. J. Clin. Invest. (2002) [Pubmed]
  20. Genetic deficiency in the chemokine receptor CCR1 protects against acute Clostridium difficile toxin A enteritis in mice. Morteau, O., Castagliuolo, I., Mykoniatis, A., Zacks, J., Wlk, M., Lu, B., Pothoulakis, C., Gerard, N.P., Gerard, C. Gastroenterology (2002) [Pubmed]
  21. Acceleration of idiopathic pneumonia syndrome (IPS) in the absence of donor MIP-1 alpha (CCL3) after allogeneic BMT in mice. Panoskaltsis-Mortari, A., Hermanson, J.R., Taras, E., Wangensteen, O.D., Serody, J.S., Blazar, B.R. Blood (2003) [Pubmed]
  22. A310 helical turn is essential for the proliferation-inhibiting properties of macrophage inflammatory protein-1 alpha (CCL3). Ottersbach, K., McLean, J., Isaacs, N.W., Graham, G.J. Blood (2006) [Pubmed]
  23. Inosine reduces systemic inflammation and improves survival in septic shock induced by cecal ligation and puncture. Liaudet, L., Mabley, J.G., Soriano, F.G., Pacher, P., Marton, A., Haskó, G., Szabó, C. Am. J. Respir. Crit. Care Med. (2001) [Pubmed]
  24. The role of lipolysis in mediating the proinflammatory effects of very low density lipoproteins in mouse peritoneal macrophages. Saraswathi, V., Hasty, A.H. J. Lipid Res. (2006) [Pubmed]
  25. Purification and biochemical characterization of the D6 chemokine receptor. Blackburn, P.E., Simpson, C.V., Nibbs, R.J., O'Hara, M., Booth, R., Poulos, J., Isaacs, N.W., Graham, G.J. Biochem. J. (2004) [Pubmed]
  26. Macrophage inflammatory protein-1alpha plays a crucial role in concanavalin A-induced liver injury through induction of proinflammatory cytokines in mice. Okamoto, S., Yokohama, S., Yoneda, M., Haneda, M., Nakamura, K. Hepatol. Res. (2005) [Pubmed]
  27. Differential expression and regulation of macrophage inflammatory protein (MIP)-1alpha and MIP-2 genes by alveolar and peritoneal macrophages in LPS-hyporesponsive C3H/HeJ mice. Wang, M.J., Jeng, K.C., Shih, P.C. Cell. Immunol. (2000) [Pubmed]
  28. Granulocyte macrophage colony-stimulating factor and interleukin-3 regulate chemokine and chemokine receptor expression in bone marrow macrophages. Jarmin, D.I., Nibbs, R.J., Jamieson, T., de Bono, J.S., Graham, G.J. Exp. Hematol. (1999) [Pubmed]
  29. Macrophage inflammatory protein-2 and KC induce chemokine production by mouse astrocytes. Luo, Y., Fischer, F.R., Hancock, W.W., Dorf, M.E. J. Immunol. (2000) [Pubmed]
  30. Transforming growth factor beta: is it a downregulator of stem cell inhibition by macrophage inflammatory protein 1 alpha? Maltman, J., Pragnell, I.B., Graham, G.J. J. Exp. Med. (1993) [Pubmed]
  31. Memory CD8+ T cells mediate antibacterial immunity via CCL3 activation of TNF/ROI+ phagocytes. Narni-Mancinelli, E., Campisi, L., Bassand, D., Cazareth, J., Gounon, P., Glaichenhaus, N., Lauvau, G. J. Exp. Med. (2007) [Pubmed]
  32. Novel chemokine responsiveness and mobilization of neutrophils during sepsis. Speyer, C.L., Gao, H., Rancilio, N.J., Neff, T.A., Huffnagle, G.B., Sarma, J.V., Ward, P.A. Am. J. Pathol. (2004) [Pubmed]
  33. RANTES-induced chemokine cascade in dendritic cells. Fischer, F.R., Luo, Y., Luo, M., Santambrogio, L., Dorf, M.E. J. Immunol. (2001) [Pubmed]
  34. Antiinflammatory effect of retrovirally transfected interleukin-10 on monosodium urate monohydrate crystal-induced acute inflammation in murine air pouches. Murakami, Y., Akahoshi, T., Kawai, S., Inoue, M., Kitasato, H. Arthritis Rheum. (2002) [Pubmed]
  35. Defects in the generation of IFN-gamma are overcome to control infection with Leishmania donovani in CC chemokine receptor (CCR) 5-, macrophage inflammatory protein-1 alpha-, or CCR2-deficient mice. Sato, N., Kuziel, W.A., Melby, P.C., Reddick, R.L., Kostecki, V., Zhao, W., Maeda, N., Ahuja, S.K., Ahuja, S.S. J. Immunol. (1999) [Pubmed]
  36. Experimental autoimmune encephalomyelitis on the SJL mouse: effect of gamma delta T cell depletion on chemokine and chemokine receptor expression in the central nervous system. Rajan, A.J., Asensio, V.C., Campbell, I.L., Brosnan, C.F. J. Immunol. (2000) [Pubmed]
  37. Langerhans cells are the major source of mRNA for IL-1 beta and MIP-1 alpha among unstimulated mouse epidermal cells. Matsue, H., Cruz, P.D., Bergstresser, P.R., Takashima, A. J. Invest. Dermatol. (1992) [Pubmed]
  38. Role of MCP-1 and MIP-1alpha in retinal neovascularization during postischemic inflammation in a mouse model of retinal neovascularization. Yoshida, S., Yoshida, A., Ishibashi, T., Elner, S.G., Elner, V.M. J. Leukoc. Biol. (2003) [Pubmed]
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