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Gene Review

Ltb4r1  -  leukotriene B4 receptor 1

Mus musculus

Synonyms: BLT1, BLTR, Bltr, LTB4-R 1, LTB4-R1, ...
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Disease relevance of Ltb4r1

  • The disease severity correlated well with histopathology, including loss of joint architecture, inflammatory cell infiltration, fibrosis, pannus formation, and bone erosion in joints of BLT1/BLT2(+/+) animals and a total absence of disease pathology in leukotriene receptor-deficient mice [1].
  • However, among the 16 HIV/SIV strains tested, the human BLT receptor did not act as a coreceptor for virus entry into CD4-expressing cells based on infection and cell-cell fusion assays [2].
  • PURPOSE: To investigate the role of leukotriene B4 (LTB4) and its receptor BLT1 in the pathogenesis of mouse uveitis [3].
  • To determine the importance of BLT-1 in atherogenesis, we crossed BLT-1-null mice with apolipoprotein (apo)-E-deficient mice, which develop severe atherosclerosis [4].
  • Oral administration of LTB4 receptor antagonists either as a pre-treatment or post-treatment attenuated TPA-induced edema and influx of neutrophils [5].
  • We have shown that BLT1 contributes to the frequency and size of abdominal aortic aneurysms in mice and that BLT1 deletion in turn inhibits proinflammatory circuits and enzymes that modulate vessel wall integrity [6].

High impact information on Ltb4r1


Chemical compound and disease context of Ltb4r1


Biological context of Ltb4r1


Anatomical context of Ltb4r1

  • Because LXA4 and aspirin-triggered 15-epimeric LXA4 (ATL) selectively regulate leukocyte responses, they were tested in BLTR transgenic mice [18].
  • Also, in BLTR transgenic mice, 5-LO expression and product formation were selectively increased in exudates, demonstrating that receptor overexpression amplifies proinflammatory circuits [18].
  • In 5-lipoxygenase-deficient mice, the absence of leukotriene B4 biosynthesis did not detectably alter m-BLT receptor binding in membranes obtained from glycogen-elicited neutrophils [2].
  • In Xenopus laevis melanophores transiently expressing m-BLTR, LTB4 induced the aggregation of pigment granules, confirming the inhibition of cAMP production induced by LTB4 [2].
  • The animals were then treated with and without the BLT1 receptor antagonist, CP105696, at the disease onset after immunization or at day 0 or day 6 after T-cell transfer [3].

Associations of Ltb4r1 with chemical compounds

  • Isolation of the m-BLTR gene will form the basis of future experiments to elucidate the selective role of LTB4, as opposed to cysteinyl-leukotrienes, in murine models of inflammation [2].
  • Membrane fractions of human embryonic kidney 293 cells stably expressing m-BLTR demonstrated a high affinity and specific binding for leukotriene B4 (LTB4, Kd = 0.24 +/- 0.03 nM) [2].
  • Several BLT1 antagonists, including U 75302, failed to inhibit LTB(4) binding to BLT2 [14].
  • These data are the first to show both a functional and an essential role for BLT1 in allergen-mediated CD8+ T(EFF) recruitment into the lung and development of AHR and airway inflammation [19].
  • The LTB4 receptor antagonist, SC-41930, inhibited the inflammatory response to TPA but had little effect on that initiated by AA [20].

Physical interactions of Ltb4r1

  • Leukotriene B(4) (LTB(4)) and leukotriene C(4) (LTC(4)) act through G protein-coupled receptors LTB(4) receptor (BLTR) and Cys-LTR, respectively [9].

Regulatory relationships of Ltb4r1

  • Here, we developed a novel murine model of acute lung rejection to demonstrate that BLT1 controls effector CD8+ T cell trafficking into the lung and that disruption of BLT1 signaling in CD8+ T cells reduces lung inflammation and mortality in the model [21].
  • Neutrophil recruitment by C5a in vivo required amplification via leukotriene B(4), because both C5a-mediated leukocyte recruitment into the peritoneal cavity and tumor regression were suppressed in leukotriene B(4)R-deficient (BLT-1(-/-)) mice [22].

Other interactions of Ltb4r1

  • Taken together, these results suggest a role for leukotrienes in acute inflammation induced by TPA and possible utility of this model to test in vivo 5-LO inhibitors and LTB4 receptor antagonists [5].
  • Homozygous low-density receptor knockout (LDLr(-/-)) mice and apolipoprotein E deficient (apoE(-/-)) mice were treated with a specific LTB4 receptor antagonist, CP-105,696, for 35 days [23].
  • This is the first report that describes a pathologic role for BLT1-mediated T lymphocyte recruitment in disease and identifies BLT1 as a potential therapeutic target after lung transplantation [21].
  • A LTB4 receptor antagonist, SC-41930 [7-(3-(4-acetyl-3-methoxy-2-propylphenoxy)-propoxy]-3,4-dihydro-8- propyl-2H-1-benzopyran-2-carboxylic acid) and an LTD4 receptor antagonist, LY-171883 [1-(2-hydroxy-3-propyl-4-(4-1H-tetrazol-5-yl)butoxy-phenyl) ethanone)] (i.v.) attenuated influx of neutrophils and associated LTB4 biosynthesis [24].
  • Attenuated symptoms were accompanied by reduced IgE production, and accumulation of IL-5 and IL-13 in bronchoalveolar lavage fluid, suggesting attenuated Th2-type immune response in BLT1-null mice [25].

Analytical, diagnostic and therapeutic context of Ltb4r1

  • Leukotriene B4 receptor transgenic mice reveal novel protective roles for lipoxins and aspirin-triggered lipoxins in reperfusion [18].
  • Despite excessive PMN recruitment in BLTR transgenic mice, intravenous injection of ATL sharply diminished reperfusion-initiated PMN trafficking to remote organs, and topical application of LX was protective in acute dermal inflammation [18].
  • In a model of collagen-induced arthritis on the C57BL/6 background, the BLT1/BLT2(-/-) as well as the previously described BLT1(-/-) animals showed complete protection from disease development [1].
  • Deletion of BLT-1 significantly reduced the lesion formation in apo-E-/- mice only during initiating stages (4 and 8 weeks) but had no effect on the lesion size in mice fed atherogenic diet for 19 weeks [4].
  • BLT1-mediated T cell trafficking is critical for rejection and obliterative bronchiolitis after lung transplantation [21].


  1. Targeted Disruption of Leukotriene B4 Receptors BLT1 and BLT2: A Critical Role for BLT1 in Collagen-Induced Arthritis in Mice. Shao, W.H., Del Prete, A., Bock, C.B., Haribabu, B. J. Immunol. (2006) [Pubmed]
  2. Leukotriene binding, signaling, and analysis of HIV coreceptor function in mouse and human leukotriene B4 receptor-transfected cells. Martin, V., Ronde, P., Unett, D., Wong, A., Hoffman, T.L., Edinger, A.L., Doms, R.W., Funk, C.D. J. Biol. Chem. (1999) [Pubmed]
  3. Blockade of the interaction of leukotriene b4 with its receptor prevents development of autoimmune uveitis. Liao, T., Ke, Y., Shao, W.H., Haribabu, B., Kaplan, H.J., Sun, D., Shao, H. Invest. Ophthalmol. Vis. Sci. (2006) [Pubmed]
  4. Role of leukotriene B4 receptors in the development of atherosclerosis: potential mechanisms. Subbarao, K., Jala, V.R., Mathis, S., Suttles, J., Zacharias, W., Ahamed, J., Ali, H., Tseng, M.T., Haribabu, B. Arterioscler. Thromb. Vasc. Biol. (2004) [Pubmed]
  5. Phorbol ester-induced dermal inflammation in mice: evaluation of inhibitors of 5-lipoxygenase and antagonists of leukotriene B4 receptor. Rao, T.S., Yu, S.S., Djuric, S.W., Isakson, P.C. Journal of lipid mediators and cell signalling. (1994) [Pubmed]
  6. Inhibited aortic aneurysm formation in BLT1-deficient mice. Ahluwalia, N., Lin, A.Y., Tager, A.M., Pruitt, I.E., Anderson, T.J., Kristo, F., Shen, D., Cruz, A.R., Aikawa, M., Luster, A.D., Gerszten, R.E. J. Immunol. (2007) [Pubmed]
  7. Leukotriene B4 and BLT1 control cytotoxic effector T cell recruitment to inflamed tissues. Goodarzi, K., Goodarzi, M., Tager, A.M., Luster, A.D., von Andrian, U.H. Nat. Immunol. (2003) [Pubmed]
  8. Leukotriene B4 receptor BLT1 mediates early effector T cell recruitment. Tager, A.M., Bromley, S.K., Medoff, B.D., Islam, S.A., Bercury, S.D., Friedrich, E.B., Carafone, A.D., Gerszten, R.E., Luster, A.D. Nat. Immunol. (2003) [Pubmed]
  9. Targeted disruption of the leukotriene B(4) receptor in mice reveals its role in inflammation and platelet-activating factor-induced anaphylaxis. Haribabu, B., Verghese, M.W., Steeber, D.A., Sellars, D.D., Bock, C.B., Snyderman, R. J. Exp. Med. (2000) [Pubmed]
  10. Requirement for leukotriene B4 receptor 1 in allergen-induced airway hyperresponsiveness. Miyahara, N., Takeda, K., Miyahara, S., Matsubara, S., Koya, T., Joetham, A., Krishnan, E., Dakhama, A., Haribabu, B., Gelfand, E.W. Am. J. Respir. Crit. Care Med. (2005) [Pubmed]
  11. Leukotriene B4 receptor (BLT-1) modulates neutrophil influx into the peritoneum but not the lung and liver during surgically induced bacterial peritonitis in mice. Scott, M.J., Cheadle, W.G., Hoth, J.J., Peyton, J.C., Subbarao, K., Shao, W.H., Haribabu, B. Clin. Diagn. Lab. Immunol. (2004) [Pubmed]
  12. 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]
  13. A novel approach of targeted ablation of mammary carcinoma cells through luteinizing hormone receptors using Hecate-CGbeta conjugate. Bodek, G., Rahman, N.A., Zaleska, M., Soliymani, R., Lankinen, H., Hansel, W., Huhtaniemi, I., Ziecik, A.J. Breast Cancer Res. Treat. (2003) [Pubmed]
  14. 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]
  15. Leukotriene B4 plays a critical role in the progression of collagen-induced arthritis. Griffiths, R.J., Pettipher, E.R., Koch, K., Farrell, C.A., Breslow, R., Conklyn, M.J., Smith, M.A., Hackman, B.C., Wimberly, D.J., Milici, A.J. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  16. Leukotriene B4: metabolism and signal transduction. Yokomizo, T., Izumi, T., Shimizu, T. Arch. Biochem. Biophys. (2001) [Pubmed]
  17. Effect of LY293111 in combination with gemcitabine in colonic cancer. Hennig, R., Ding, X.Z., Tong, W.G., Witt, R.C., Jovanovic, B.D., Adrian, T.E. Cancer Lett. (2004) [Pubmed]
  18. Leukotriene B4 receptor transgenic mice reveal novel protective roles for lipoxins and aspirin-triggered lipoxins in reperfusion. Chiang, N., Gronert, K., Clish, C.B., O'Brien, J.A., Freeman, M.W., Serhan, C.N. J. Clin. Invest. (1999) [Pubmed]
  19. Leukotriene B4 receptor-1 is essential for allergen-mediated recruitment of CD8+ T cells and airway hyperresponsiveness. Miyahara, N., Takeda, K., Miyahara, S., Taube, C., Joetham, A., Koya, T., Matsubara, S., Dakhama, A., Tager, A.M., Luster, A.D., Gelfand, E.W. J. Immunol. (2005) [Pubmed]
  20. Comparative evaluation of arachidonic acid (AA)- and tetradecanoylphorbol acetate (TPA)-induced dermal inflammation. Rao, T.S., Currie, J.L., Shaffer, A.F., Isakson, P.C. Inflammation (1993) [Pubmed]
  21. BLT1-mediated T cell trafficking is critical for rejection and obliterative bronchiolitis after lung transplantation. Medoff, B.D., Seung, E., Wain, J.C., Means, T.K., Campanella, G.S., Islam, S.A., Thomas, S.Y., Ginns, L.C., Grabie, N., Lichtman, A.H., Tager, A.M., Luster, A.D. J. Exp. Med. (2005) [Pubmed]
  22. C5a-mediated leukotriene B4-amplified neutrophil chemotaxis is essential in tumor immunotherapy facilitated by anti-tumor monoclonal antibody and beta-glucan. Allendorf, D.J., Yan, J., Ross, G.D., Hansen, R.D., Baran, J.T., Subbarao, K., Wang, L., Haribabu, B. J. Immunol. (2005) [Pubmed]
  23. Leukotriene B4 receptor antagonism reduces monocytic foam cells in mice. Aiello, R.J., Bourassa, P.A., Lindsey, S., Weng, W., Freeman, A., Showell, H.J. Arterioscler. Thromb. Vasc. Biol. (2002) [Pubmed]
  24. In vivo characterization of zymosan-induced mouse peritoneal inflammation. Rao, T.S., Currie, J.L., Shaffer, A.F., Isakson, P.C. J. Pharmacol. Exp. Ther. (1994) [Pubmed]
  25. Absence of leukotriene B4 receptor 1 confers resistance to airway hyperresponsiveness and Th2-type immune responses. Terawaki, K., Yokomizo, T., Nagase, T., Toda, A., Taniguchi, M., Hashizume, K., Yagi, T., Shimizu, T. J. Immunol. (2005) [Pubmed]
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