In vivo assessments of mucus dynamics in the rat lung using a Gd-Cy5.5-bilabeled contrast agent for magnetic resonance and optical imaging.
Dysfunctions in mucociliary clearance are associated with the accelerated loss of lung function in several respiratory diseases. Approaches enabling the in vivo visualization of mucus dynamics in rodents at high resolution and sensitivity would be beneficial for experimental lung research. We describe the synthesis and characterization of two bilabeled amino dextran-based probes binding specifically to mucin. Labeling of secreted mucus and of mucin in goblet cells in the lungs of lipopolysaccharide-challenged rats has been demonstrated in vivo with near-infrared fluorescence and MRI and confirmed by histology. The effects of uridine triphosphate were then studied in lipopolysaccharide-challenged rats by simultaneously administering the imaging probe and the compound. The data suggest that uridine triphosphate increased the mucociliary clearance, but at the same time induced a release of mucin from goblet cells, thus not contributing to the overall reduction of mucus in the lung. The approach outlined here enables one to derive information on mucus clearance, as well as secretion. Such a global view on mucus dynamics may prove invaluable when testing new pharmacological agents aimed at improving mucociliary clearance.
Global Imaging Group, Novartis Institutes for BioMedical Research, Basel, Switzerland.
François-Xavier
FX
Blé
Philipp
P
Schmidt
Catherine
C
Cannet
Rainer
R
Kneuer
Harry
H
Karmouty-Quintana
Reinhard
R
Bergmann
Kevin
K
Coote
Henry
H
Danahay
Stefan
S
Zurbruegg
Hans-Ulrich
HU
Gremlich
Nicolau
N
Beckmann
D000818:Animals; D002232:Carbocyanines / Q000493:pharmacokinetics; D003287:Contrast Media; D005682:Gadolinium / Q000493:pharmacokinetics; D007089:Image Enhancement / Q000379:methods*; D008070:Lipopolysaccharides; D008168:Lung / Q000378:metabolism* / Q000473:pathology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008856:Microscopy, Fluorescence / Q000379:methods; D009077:Mucins / Q000378:metabolism*; D011014:Pneumonia / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D051381:Rats; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
C098793:CY5.5 cyanine dye; D002232:Carbocyanines; D003287:Contrast Media; D008070:Lipopolysaccharides; D009077:Mucins; D005682:Gadolinium