MUB40 Binds to Lactoferrin and Stands as a Specific Neutrophil Marker

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, MUB40, binds to lactoferrin, the most abundant protein stored in neutrophil-specific and tertiary granules. Lactof...

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Published inCell chemical biology Vol. 25; no. 4; pp. 483 - 493.e9
Main Authors Anderson, Mark C., Chaze, Thibault, Coïc, Yves-Marie, Injarabian, Louise, Jonsson, Friederike, Lombion, Naelle, Selimoglu-Buet, Dorothée, Souphron, Judith, Ridley, Caroline, Vonaesch, Pascale, Baron, Bruno, Arena, Ellen T., Tinevez, Jean-Yves, Nigro, Giulia, Nothelfer, Katharina, Solary, Eric, Lapierre, Valérie, Lazure, Thierry, Matondo, Mariette, Thornton, David, Sansonetti, Philippe J., Baleux, Françoise, Marteyn, Benoit S.
Format Journal Article
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Published Elsevier Ltd 19.04.2018
Cell Press
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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, MUB40, binds to lactoferrin, the most abundant protein stored in neutrophil-specific and tertiary granules. Lactoferrin is specifically produced by neutrophils among other leukocytes, making MUB40 a specific neutrophil marker. Naive mammalian neutrophils (human, guinea pig, mouse, rabbit) were labeled by fluorescent MUB40 conjugates (-Cy5, Dylight405). A peptidase-resistant retro-inverso MUB40 (RI-MUB40) was synthesized and its lactoferrin-binding property validated. Neutrophil lactoferrin secretion during in vitro Shigella infection was assessed with RI-MUB40-Cy5 using live cell microscopy. Systemically administered RI-MUB40-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 MUB40 marker will aid the study of broad ranges of inflammatory diseases. [Display omitted] •MUB40 is a 40-amino-acid peptide that interacts with neutrophil lactoferrin•MUB40 labels neutrophil-specific (β1), tertiary (β2), and secretome (γ) granules•RI-MUB40 is a proteolysis-resistant version of MUB40•Neutrophilic inflammation is revealed in vivo with RI-MUB40 systemic injection MUB40 is a universal and specific marker of mammalian neutrophils. MUB40 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 MUB40 peptides conjugated to fluorophores. Neutrophilic inflammation detection may be envisaged by combining MUB40 with non-invasive imaging.
AbstractList 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, MUB40, binds to lactoferrin, the most abundant protein stored in neutrophil-specific and tertiary granules. Lactoferrin is specifically produced by neutrophils among other leukocytes, making MUB40 a specific neutrophil marker. Naive mammalian neutrophils (human, guinea pig, mouse, rabbit) were labeled by fluorescent MUB40 conjugates (-Cy5, Dylight405). A peptidase-resistant retro-inverso MUB40 (RI-MUB40) was synthesized and its lactoferrin-binding property validated. Neutrophil lactoferrin secretion during in vitro Shigella infection was assessed with RI-MUB40-Cy5 using live cell microscopy. Systemically administered RI-MUB40-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 MUB40 marker will aid the study of broad ranges of inflammatory diseases. [Display omitted] •MUB40 is a 40-amino-acid peptide that interacts with neutrophil lactoferrin•MUB40 labels neutrophil-specific (β1), tertiary (β2), and secretome (γ) granules•RI-MUB40 is a proteolysis-resistant version of MUB40•Neutrophilic inflammation is revealed in vivo with RI-MUB40 systemic injection MUB40 is a universal and specific marker of mammalian neutrophils. MUB40 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 MUB40 peptides conjugated to fluorophores. Neutrophilic inflammation detection may be envisaged by combining MUB40 with non-invasive imaging.
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, MUB40, binds to lactoferrin, the most abundant protein stored in neutrophil-specific and tertiary granules. Lactoferrin is specifically produced by neutrophils among other leukocytes, making MUB40 a specific neutrophil marker. Naive mammalian neutrophils (human, guinea pig, mouse, rabbit) were labeled by fluorescent MUB40 conjugates (-Cy5, Dylight405). A peptidase-resistant retro-inverso MUB40 (RI-MUB40) was synthesized and its lactoferrin-binding property validated. Neutrophil lactoferrin secretion during in vitro Shigella infection was assessed with RI-MUB40-Cy5 using live cell microscopy. Systemically administered RI-MUB40-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 MUB40 marker will aid the study of broad ranges of inflammatory diseases.
Author Nigro, Giulia
Jonsson, Friederike
Chaze, Thibault
Ridley, Caroline
Injarabian, Louise
Vonaesch, Pascale
Solary, Eric
Lapierre, Valérie
Selimoglu-Buet, Dorothée
Nothelfer, Katharina
Lazure, Thierry
Tinevez, Jean-Yves
Arena, Ellen T.
Thornton, David
Baleux, Françoise
Anderson, Mark C.
Lombion, Naelle
Sansonetti, Philippe J.
Coïc, Yves-Marie
Souphron, Judith
Baron, Bruno
Matondo, Mariette
Marteyn, Benoit S.
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Issue 4
Keywords lactoferrin
MUB40
biomarker
neutrophil
imaging
MUB
Language English
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Snippet Neutrophils represent the most abundant immune cells recruited to inflamed tissues. A lack of dedicated tools has hampered their detection and study. We show...
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Publisher
StartPage 483
SubjectTerms Adult
Animals
Biochemistry, Molecular Biology
biomarker
Biomarkers
Carbocyanines
Dysentery, Bacillary
Female
Fluorescent Dyes
Guinea Pigs
Humans
imaging
Immunology
Inflammation
Lactoferrin
Life Sciences
Mice
Mice, Inbred C57BL
Middle Aged
MUB40
neutrophil
Neutrophils
Peptides
Rabbits
Shigella
Title MUB40 Binds to Lactoferrin and Stands as a Specific Neutrophil Marker
URI https://dx.doi.org/10.1016/j.chembiol.2018.01.014
https://pasteur.hal.science/pasteur-02573125
Volume 25
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