MUB 40 Binds to Lactoferrin and Stands as a Specific Neutrophil Marker

Mark C. Anderson, Thibault Chaze, Yves Marie Coïc, Louise Injarabian, Friederike Jonsson, Naelle Lombion, Dorothée Selimoglu-Buet, Judith Souphron, Caroline Ridley, Pascale Vonaesch, Bruno Baron, Ellen T. Arena, Jean Yves Tinevez, Giulia Nigro, Katharina Nothelfer, Eric Solary, Valérie Lapierre, Thierry Lazure, Mariette Matondo, David ThorntonPhilippe J. Sansonetti, Françoise Baleux, Benoit S. Marteyn

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    12 Citations (Scopus)

    Abstract

    Neutrophils represent the most abundant immune cells recruited to inflamed tissues. A lack of dedicated tools has hampered their detection and study. We show that a synthesized peptide, MUB 40 , binds to lactoferrin, the most abundant protein stored in neutrophil-specific and tertiary granules. Lactoferrin is specifically produced by neutrophils among other leukocytes, making MUB 40 a specific neutrophil marker. Naive mammalian neutrophils (human, guinea pig, mouse, rabbit) were labeled by fluorescent MUB 40 conjugates (-Cy5, Dylight405). A peptidase-resistant retro-inverso MUB 40 (RI-MUB 40 ) was synthesized and its lactoferrin-binding property validated. Neutrophil lactoferrin secretion during in vitro Shigella infection was assessed with RI-MUB 40 -Cy5 using live cell microscopy. Systemically administered RI-MUB 40 -Cy5 accumulated at sites of inflammation in a mouse arthritis inflammation model in vivo and showed usefulness as a potential tool for inflammation detection using non-invasive imaging. Improving neutrophil detection with the universal and specific MUB 40 marker will aid the study of broad ranges of inflammatory diseases. MUB 40 is a universal and specific marker of mammalian neutrophils. MUB 40 interacts with lactoferrin, stored in specific (β1), tertiary (β2), and secretome (γ) granules secreted upon stimulation. Neutrophil detection in inflamed or infected tissues is facilitated by MUB 40 peptides conjugated to fluorophores. Neutrophilic inflammation detection may be envisaged by combining MUB 40 with non-invasive imaging.

    Original languageEnglish
    Pages (from-to)483-493.e9
    JournalCell Chemical Biology
    Volume25
    Issue number4
    DOIs
    Publication statusPublished - 19 Apr 2018

    Keywords

    • MUB
    • biomarker
    • imaging
    • lactoferrin
    • neutrophil

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