TY - JOUR
T1 - Bioluminescence imaging of myeloperoxidase activity in vivo
AU - Gross, Shimon
AU - Gammon, Seth T.
AU - Moss, Britney L.
AU - Rauch, Daniel
AU - Harding, John
AU - Heinecke, Jay W.
AU - Ratner, Lee
AU - Piwnica-Worms, David
N1 - Funding Information:
We thank V. Sharma for insightful discussions. This research was funded by US National Institutes of Health grants P50 CA94056, CA105218, CA10073, CA63417 and PO1 HL030086.
PY - 2009/4
Y1 - 2009/4
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=64149109962&partnerID=8YFLogxK
U2 - 10.1038/nm.1886
DO - 10.1038/nm.1886
M3 - Article
C2 - 19305414
AN - SCOPUS:64149109962
SN - 1078-8956
VL - 15
SP - 455
EP - 461
JO - Nature Medicine
JF - Nature Medicine
IS - 4
ER -