Bioluminescence imaging of myeloperoxidase activity in vivo

Abstract

The leukocyte enzyme myeloperoxidase (MPO) is key to normal host defense mechanisms. Dysregulated MPO, however, is linked to acute and chronic inflammatory conditions, such as atherosclerosis and cancer. The authors describe a luminol-based bioluminescence imaging system that provides an optical readout of physiological levels of MPO activity in vivo. The system is demonstrated in animal models of acute dermatitis, focal arthritis and spontaneous large granular lymphocytic tumors. 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.