TY - JOUR
T1 - MUB40 Binds to Lactoferrin and Stands as a Specific Neutrophil Marker
AU - Anderson, Mark C.
AU - Chaze, Thibault
AU - Coïc, Yves Marie
AU - Injarabian, Louise
AU - Jonsson, Friederike
AU - Lombion, Naelle
AU - Selimoglu-Buet, Dorothée
AU - Souphron, Judith
AU - Ridley, Caroline
AU - Vonaesch, Pascale
AU - Baron, Bruno
AU - Arena, Ellen T.
AU - Tinevez, Jean Yves
AU - Nigro, Giulia
AU - Nothelfer, Katharina
AU - Solary, Eric
AU - Lapierre, Valérie
AU - Lazure, Thierry
AU - Matondo, Mariette
AU - Thornton, David
AU - Sansonetti, Philippe J.
AU - Baleux, Françoise
AU - Marteyn, Benoit S.
PY - 2018/4/19
Y1 - 2018/4/19
N2 - 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. 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.
AB - 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. 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.
KW - biomarker
KW - imaging
KW - lactoferrin
KW - MUB
KW - neutrophil
UR - http://www.scopus.com/inward/record.url?scp=85042318397&partnerID=8YFLogxK
U2 - 10.1016/j.chembiol.2018.01.014
DO - 10.1016/j.chembiol.2018.01.014
M3 - Article
AN - SCOPUS:85042318397
SN - 2451-9456
VL - 25
SP - 483-493.e9
JO - Cell Chemical Biology
JF - Cell Chemical Biology
IS - 4
ER -
