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A genetically encoded sensor for visualizing leukotriene B4 gradients in vivo

Author

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  • Szimonetta Xénia Tamás

    (Faculty of Medicine
    Hungarian Academy of Sciences and Semmelweis University
    Semmelweis University)

  • Benoit Thomas Roux

    (Faculty of Medicine
    Semmelweis University)

  • Boldizsár Vámosi

    (Faculty of Medicine)

  • Fabian Gregor Dehne

    (Faculty of Medicine
    Semmelweis University)

  • Anna Török

    (Faculty of Medicine
    Semmelweis University)

  • László Fazekas

    (Faculty of Medicine
    Hungarian Academy of Sciences and Semmelweis University
    Semmelweis University)

  • Balázs Enyedi

    (Faculty of Medicine
    Hungarian Academy of Sciences and Semmelweis University
    Semmelweis University)

Abstract

Leukotriene B4 (LTB4) is a potent lipid chemoattractant driving inflammatory responses during host defense, allergy, autoimmune and metabolic diseases. Gradients of LTB4 orchestrate leukocyte recruitment and swarming to sites of tissue damage and infection. How LTB4 gradients form and spread in live tissues to regulate these processes remains largely elusive due to the lack of suitable tools for monitoring LTB4 levels in vivo. Here, we develop GEM-LTB4, a genetically encoded green fluorescent LTB4 biosensor based on the human G-protein-coupled receptor BLT1. GEM-LTB4 shows high sensitivity, specificity and a robust fluorescence increase in response to LTB4 without affecting downstream signaling pathways. We use GEM-LTB4 to measure ex vivo LTB4 production of murine neutrophils. Transgenic expression of GEM-LTB4 in zebrafish allows the real-time visualization of both exogenously applied and endogenously produced LTB4 gradients. GEM-LTB4 thus serves as a broadly applicable tool for analyzing LTB4 dynamics in various experimental systems and model organisms.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40326-6
    DOI: 10.1038/s41467-023-40326-6
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    References listed on IDEAS

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    1. Caroline Coombs & Antonios Georgantzoglou & Hazel A. Walker & Julian Patt & Nicole Merten & Hugo Poplimont & Elisabeth M. Busch-Nentwich & Sarah Williams & Christina Kotsi & Evi Kostenis & Milka Sarri, 2019. "Chemokine receptor trafficking coordinates neutrophil clustering and dispersal at wounds in zebrafish," Nature Communications, Nature, vol. 10(1), pages 1-17, December.
    2. 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.
    3. Katharina Löffler & Tim Scherr & Ralf Mikut, 2021. "A graph-based cell tracking algorithm with few manually tunable parameters and automated segmentation error correction," PLOS ONE, Public Library of Science, vol. 16(9), pages 1-28, September.
    4. Sa Kan Yoo & Taylor W. Starnes & Qing Deng & Anna Huttenlocher, 2011. "Lyn is a redox sensor that mediates leukocyte wound attraction in vivo," Nature, Nature, vol. 480(7375), pages 109-112, December.
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