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Gene Review

LTB4R  -  leukotriene B4 receptor

Homo sapiens

Synonyms: BLT, BLT1, BLTR, CMKRL1, Chemoattractant receptor-like 1, ...
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Disease relevance of LTB4R


High impact information on LTB4R

  • Furthermore, CHO cells expressing exogenous BLTR showed marked chemotactic responses towards low concentrations of LTB4 in a pertussis-toxin-sensitive manner [5].
  • Here we report the cloning of the complementary DNA encoding a cell-surface LTB4 receptor that is highly expressed in human leukocytes [5].
  • A unique requirement for the leukotriene B4 receptor BLT1 for neutrophil recruitment in inflammatory arthritis [6].
  • The promoter region of the BLT1 gene is localized within the open reading frame (ORF) of the BLT2 gene, which encodes a low-affinity receptor for LTB(4) (Yokomizo, T., K. Kato, K. Terawaki, T. Izumi, and T. Shimizu. 2000. J. Exp. Med. 192:421-431) [7].
  • BLT1, a high-affinity receptor for LTB(4) (originally termed BLT), is expressed exclusively in inflammatory cells and is inducible in macrophages upon activation [7].

Chemical compound and disease context of LTB4R


Biological context of LTB4R


Anatomical context of LTB4R

  • The P2Y7 receptor is functionally coupled to phospholipase C in COS-7 cells transiently expressing this receptor [12].
  • The P2Y7 receptor mRNA is abundantly present in the human heart and the skeletal muscle, moderately in the brain and liver, but not in the other tissues tested [12].
  • In contrast, leukocytes infiltrating synovial fluid predominantly expressed BLT1 mRNA in patients with RA [13].
  • Furthermore, pretreatment of neutrophils with a LTB4-receptor antagonist, LY 255283, blocked the AA- and LTB4-induced activation of PLA2 but did not influence the action of 5-HETE [15].
  • Pretreatment of mBMMCs with stem cell factor significantly down-regulated expression of BLT1 and BLT2 mRNA and inhibited their migration to LTB4 [14].

Associations of LTB4R with chemical compounds

  • The P2Y7 cDNA was transiently expressed in COS-7 cells: binding studies thereon showed a very high affinity for ATP (37 +/- 6 nM), much less for UTP and ADP (approximately 1300 nM), and a novel rank order of affinities in the binding series studied of 8 nucleotides and suramin [12].
  • Results. BLT2 (the low-affinity receptor for LTB4) showed stronger expression than BLT1 (the high-affinity receptor) in actively inflamed synovial tissue from patients with RA [13].
  • The nascent LTB4 is then released to act on the LTB4 receptor and thereby promote further activation of the 85-kDa PLA2 [15].
  • Augmented expression of BLT1 by Dex was associated with enhanced functional activities, such as LTB(4)-induced intracellular calcium mobilization and chemotaxis [16].
  • BLT1 calcium signalling was sensitive to the activity of protein kinase C (PKC), protein kinase A (PKA) and protein-tyrosine kinases (PTKs), as well as changes in membrane cholesterol levels and treatments that are known to disrupt normal membrane physiology and/or lipid rafts [17].

Regulatory relationships of LTB4R


Other interactions of LTB4R

  • This receptor, designated P2Y7, has 352 amino acids and shares 23-30% amino acid identity with the P2Y1-P2Y6 purinoceptors [12].
  • This induction is mediated through the BLT1 pathway increasing MCP-1 transcription [22].
  • Cancer-related increases in methylation of only two studied genes, LTB4R and MTHFR, which were appreciably methylated even in control tissues, were associated with DNMT1 RNA levels [23].
  • Flow cytometric analysis of fresh peripheral blood cells revealed that classical (CD14(++)CD16(-)) monocytes express high levels of BLT1 and CCR2 and that both receptors are down-regulated on CD14(+)CD16(+) monocytes [24].
  • Our findings thus suggest that Thr(308) is a major residue involved in GRK6-mediated desensitization of BLT1 signaling [25].

Analytical, diagnostic and therapeutic context of LTB4R


  1. Leukotriene B4 receptor antagonist LY293111 inhibits proliferation and induces apoptosis in human pancreatic cancer cells. Tong, W.G., Ding, X.Z., Hennig, R., Witt, R.C., Standop, J., Pour, P.M., Adrian, T.E. Clin. Cancer Res. (2002) [Pubmed]
  2. Leukotriene B4 signaling through NF-kappaB-dependent BLT1 receptors on vascular smooth muscle cells in atherosclerosis and intimal hyperplasia. Bäck, M., Bu, D.X., Bränström, R., Sheikine, Y., Yan, Z.Q., Hansson, G.K. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  3. Activation of the human neutrophil 5-lipoxygenase by leukotriene B4. McDonald, P.P., McColl, S.R., Naccache, P.H., Borgeat, P. Br. J. Pharmacol. (1992) [Pubmed]
  4. Regulatory expression of lipoxin A4 receptor in physiologically estrus cycle and pathologically endometriosis. Motohashi, E., Kawauchi, H., Endo, H., Kondo, H., Kitasato, H., Kuramoto, H., Majima, M., Unno, N., Hayashi, I. Biomed. Pharmacother. (2005) [Pubmed]
  5. A G-protein-coupled receptor for leukotriene B4 that mediates chemotaxis. Yokomizo, T., Izumi, T., Chang, K., Takuwa, Y., Shimizu, T. Nature (1997) [Pubmed]
  6. A unique requirement for the leukotriene B4 receptor BLT1 for neutrophil recruitment in inflammatory arthritis. Kim, N.D., Chou, R.C., Seung, E., Tager, A.M., Luster, A.D. J. Exp. Med. (2006) [Pubmed]
  7. Cell-specific transcriptional regulation of human leukotriene B(4) receptor gene. Kato, K., Yokomizo, T., Izumi, T., Shimizu, T. J. Exp. Med. (2000) [Pubmed]
  8. Oral efficacy of a leukotriene B4 receptor antagonist in colitic cotton-top tamarins. Fretland, D., Sanderson, T., Smith, P., Adams, L., Carson, R., Fuhr, J., Tanner, J., Clapp, N. Gut (1995) [Pubmed]
  9. Leukotriene B4 receptor inhibitor LY293111 induces cell cycle arrest and apoptosis in human anaplastic large-cell lymphoma cells via JNK phosphorylation. Zhang, W., McQueen, T., Schober, W., Rassidakis, G., Andreeff, M., Konopleva, M. Leukemia (2005) [Pubmed]
  10. Leukotriene B4: metabolism and signal transduction. Yokomizo, T., Izumi, T., Shimizu, T. Arch. Biochem. Biophys. (2001) [Pubmed]
  11. Eicosapentaenoic acid modulates neutrophil leukotriene B4 receptor expression in cystic fibrosis. Lawrence, R.H., Sorrell, T.C. Clin. Exp. Immunol. (1994) [Pubmed]
  12. Molecular cloning of a novel P2 purinoceptor from human erythroleukemia cells. Akbar, G.K., Dasari, V.R., Webb, T.E., Ayyanathan, K., Pillarisetti, K., Sandhu, A.K., Athwal, R.S., Daniel, J.L., Ashby, B., Barnard, E.A., Kunapuli, S.P. J. Biol. Chem. (1996) [Pubmed]
  13. Differential expression of leukotriene B4 receptor subtypes (BLT1 and BLT2) in human synovial tissues and synovial fluid leukocytes of patients with rheumatoid arthritis. Hashimoto, A., Endo, H., Hayashi, I., Murakami, Y., Kitasato, H., Kono, S., Matsui, T., Tanaka, S., Nishimura, A., Urabe, K., Itoman, M., Kondo, H. J. Rheumatol. (2003) [Pubmed]
  14. Leukotriene B4 receptors BLT1 and BLT2: expression and function in human and murine mast cells. Lundeen, K.A., Sun, B., Karlsson, L., Fourie, A.M. J. Immunol. (2006) [Pubmed]
  15. 5-Lipoxygenase products modulate the activity of the 85-kDa phospholipase A2 in human neutrophils. Wijkander, J., O'Flaherty, J.T., Nixon, A.B., Wykle, R.L. J. Biol. Chem. (1995) [Pubmed]
  16. Glucocorticoids up-regulate leukotriene B4 receptor-1 expression during neutrophilic differentiation of HL-60 cells. Obinata, H., Yokomizo, T., Shimizu, T., Izumi, T. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  17. Exploring the pharmacology of the leukotriene B4 receptor BLT1, without the confounding effects of BLT2. Sabirsh, A., Bristulf, J., Owman, C. Eur. J. Pharmacol. (2004) [Pubmed]
  18. Adhesion-dependent release of elastase from human neutrophils in a novel, flow-based model: specificity of different chemotactic agents. Rainger, G.E., Rowley, A.F., Nash, G.B. Blood (1998) [Pubmed]
  19. Blockade of leukotriene b(4) signaling pathway induces apoptosis and suppresses cell proliferation in colon cancer. Ihara, A., Wada, K., Yoneda, M., Fujisawa, N., Takahashi, H., Nakajima, A. J. Pharmacol. Sci. (2007) [Pubmed]
  20. The regulation of CD11b integrin levels on human blood leukocytes and leukotriene B4-stimulated skin by a specific leukotriene B4 receptor antagonist (LY293111). van Pelt, J.P., de Jong, E.M., van Erp, P.E., Mitchell, M.I., Marder, P., Spaethe, S.M., van Hooijdonk, C.A., Kuijpers, A.L., van de Kerkhof, P.C. Biochem. Pharmacol. (1997) [Pubmed]
  21. Tumour necrosis factors modulate the affinity state of the leukotriene B4 receptor on human neutrophils. Brom, J., Knöller, J., Köller, M., König, W. Immunology (1988) [Pubmed]
  22. Leukotriene B4 strongly increases monocyte chemoattractant protein-1 in human monocytes. Huang, L., Zhao, A., Wong, F., Ayala, J.M., Struthers, M., Ujjainwalla, F., Wright, S.D., Springer, M.S., Evans, J., Cui, J. Arterioscler. Thromb. Vasc. Biol. (2004) [Pubmed]
  23. Quantitative analysis of associations between DNA hypermethylation, hypomethylation, and DNMT RNA levels in ovarian tumors. Ehrlich, M., Woods, C.B., Yu, M.C., Dubeau, L., Yang, F., Campan, M., Weisenberger, D.J., Long, T., Youn, B., Fiala, E.S., Laird, P.W. Oncogene (2006) [Pubmed]
  24. Pro- and anti-inflammatory substances modulate expression of the leukotriene B4 receptor, BLT1, in human monocytes. Pettersson, A., Sabirsh, A., Bristulf, J., Kidd-Ljunggren, K., Ljungberg, B., Owman, C., Karlsson, U. J. Leukoc. Biol. (2005) [Pubmed]
  25. Threonine 308 within a putative casein kinase 2 site of the cytoplasmic tail of leukotriene B(4) receptor (BLT1) is crucial for ligand-induced, G-protein-coupled receptor-specific kinase 6-mediated desensitization. Gaudreau, R., Le Gouill, C., Venne, M.H., Stankova, J., Rola-Pleszczynski, M. J. Biol. Chem. (2002) [Pubmed]
  26. A second leukotriene B(4) receptor, BLT2. A new therapeutic target in inflammation and immunological disorders. Yokomizo, T., Kato, K., Terawaki, K., Izumi, T., Shimizu, T. J. Exp. Med. (2000) [Pubmed]
  27. Leukotriene B4 plays a pivotal role in CD40-dependent activation of chronic B lymphocytic leukemia cells. Runarsson, G., Liu, A., Mahshid, Y., Feltenmark, S., Pettersson, A., Klein, E., Björkholm, M., Claesson, H.E. Blood (2005) [Pubmed]
  28. First-generation monoclonal antibodies identifying the human leukotriene B(4) receptor-1. Pettersson, A., Boketoft, A., Sabirsh, A., Nilsson, N.E., Kotarsky, K., Olde, B., Owman, C. Biochem. Biophys. Res. Commun. (2000) [Pubmed]
  29. Genomic organization of the leukotriene B(4) receptor locus of human chromosome 14. Nilsson, N.E., Tryselius, Y., Owman, C. Biochem. Biophys. Res. Commun. (2000) [Pubmed]
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