Bioluminescence imaging of myeloperoxidase activity in vivo.
The myeloperoxidase (MPO) system of activated phagocytes is central to normal host defense mechanisms, and dysregulated MPO contributes to the pathogenesis of inflammatory disease states ranging from atherosclerosis to cancer. Here we show that upon systemic administration, the small molecule luminol enables noninvasive bioluminescence imaging (BLI) of MPO activity in vivo. Luminol-BLI allowed quantitative longitudinal monitoring of MPO activity in animal models of acute dermatitis, mixed allergic contact hypersensitivity, focal arthritis and spontaneous large granular lymphocytic tumors. Bioluminescence colocalized with histological sites of inflammation and was totally abolished in gene-deleted Mpo(-/-) mice, despite massive tissue infiltration of neutrophils and activated eosinophils, indicating that eosinophil peroxidase did not contribute to luminol-BLI in vivo. Thus, luminol-BLI provides a noninvasive, specific and highly sensitive optical readout of phagocyte-mediated MPO activity in vivo and may enable new diagnostic applications in a wide range of acute and chronic inflammatory conditions.
Gross
Shimon
S
Molecular Imaging Center, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri, USA.
Gammon
Seth T
ST
Moss
Britney L
BL
Rauch
Daniel
D
Harding
John
J
Heinecke
Jay W
JW
Ratner
Lee
L
Piwnica-Worms
David
D
D000818:Animals; D001168:Arthritis / Q000201:enzymology; D050197:Atherosclerosis / Q000503:physiopathology; D003872:Dermatitis / Q000201:enzymology; D003877:Dermatitis, Contact / Q000201:enzymology; D004195:Disease Models, Animal; D017353:Gene Deletion; D006801:Humans; D007249:Inflammation / Q000201:enzymology / Q000503:physiopathology / Q000517:prevention & control; D008163:Luminescent Measurements / Q000379:methods*; D008165:Luminol / Q000378:metabolism; D008223:Lymphoma / Q000201:enzymology; D051379:Mice; D009369:Neoplasms / Q000503:physiopathology; D009195:Peroxidase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D010586:Phagocytes / Q000201:enzymology
D008165:Luminol; D009195:Peroxidase