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A G-protein-coupled receptor for leukotriene B4 that mediates chemotaxis

Author

Listed:
  • Takehiko Yokomizo

    (Cardiovascular, Faculty of Medicine, The University of Tokyo)

  • Takashi Izumi

    (Cardiovascular, Faculty of Medicine, The University of Tokyo)

  • Kyungho Chang

    (The University of Tokyo)

  • Yoh Takuwa

    (The University of Tokyo)

  • Takao Shimizu

    (Cardiovascular, Faculty of Medicine, The University of Tokyo)

Abstract

Leukotriene B4(LTB4)1 is a potent chemoattractant that is primarily involved in inflammation, immune responses and host defence against infection2. LTB4 activates inflammatory cells by binding to its cell-surface receptor (BLTR)3. LTB4 can also bind and activate the intranuclear transcription factor PPARα, resulting in the activation of genes that terminate inflammatory processes4. Here we report the cloning of the complementary DNA encoding a cell-surface LTB4 receptor that is highly expressed in human leukocytes. Using a subtraction strategy, we isolated two cDNA clones (HL-1 and HL-5) from retinoic acid-differentiated HL-60 cells. These two clones contain identical open reading frames encoding a protein of 352 amino acids and predicted to contain seven membrane-spanning domains, but different 5′-untranslated regions. Membrane fractions of Cos-7 cells transfected with an expression construct containing the open reading frame of HL-5 showed specific LTB4 binding, with a Kd(0.154nM) comparable to that observed in retinoic acid-differentiated HL-60 cells. In CHO cells stably expressing this receptor, LTB4 induced increases in intracellular calcium, D-myo-inositol-1,4,5-triphosphate (InsP3) accumulation, and inhibition of adenylyl cyclase. Furthermore, CHO cells expressing exogenous BLTR showed marked chemotactic responses towards low concentrations of LTB4 in a pertussis-toxin-sensitive manner. Our findings, together with previous reports4,5, show that LTB4 is a unique lipid mediator that interacts with both cell-surface and nuclear receptors.

Suggested Citation

  • Takehiko Yokomizo & Takashi Izumi & Kyungho Chang & Yoh Takuwa & Takao Shimizu, 1997. "A G-protein-coupled receptor for leukotriene B4 that mediates chemotaxis," Nature, Nature, vol. 387(6633), pages 620-624, June.
    • Handle: RePEc:nat:nature:v:387:y:1997:i:6633:d:10.1038_42506
    DOI: 10.1038/42506
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    Cited by:

    1. Na Wang & Xinheng He & Jing Zhao & Hualiang Jiang & Xi Cheng & Yu Xia & H. Eric Xu & Yuanzheng He, 2022. "Structural basis of leukotriene B4 receptor 1 activation," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    2. Stefano Evangelista, 2018. "Pharmacological Analysis of the Potentiation of Carrageenin-Induced Paw Oedema by Reactive Blue 2," Biomedical Journal of Scientific & Technical Research, Biomedical Research Network+, LLC, vol. 2(4), pages 2725-2727, February.
    3. Zhou Hong & Daping Xu & Shunde Su & Renhua Zheng & Jisen Shi, 2019. "Establishment of Methylation Sensitive Suppression Subtraction Hybridization Analysis and Isolation Of 5’cpg Islands Fragments in Chinese Fir Genomic DNA," Biomedical Journal of Scientific & Technical Research, Biomedical Research Network+, LLC, vol. 15(1), pages 1-9, February.
    4. Szimonetta Xénia Tamás & Benoit Thomas Roux & Boldizsár Vámosi & Fabian Gregor Dehne & Anna Török & László Fazekas & Balázs Enyedi, 2023. "A genetically encoded sensor for visualizing leukotriene B4 gradients in vivo," Nature Communications, Nature, vol. 14(1), pages 1-11, December.

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