In vivo imaging of inflammatory phagocytes

Inflammation contributes to the pathophysiology of many diseases. In this report, we present noninvasive bioluminescence imaging methods that distinguish acute and chronic inflammation in mouse models. Systemic delivery of luminol (5-amino-2,3-dihydro-1,4-phthalazinedione) enables detection of acute inflammation largely mediated by tissue-infiltrating neutrophils, whose myeloperoxidase (MPO) activity is required for luminol bioluminescence. In contrast, bioluminescence from injection of lucigenin (bis-N-methylacridinium nitrate) closely correlates with late phase and chronic inflammation. Lucigenin bioluminescence is independent of MPO and, instead, requires phagocyte NADPH oxidase (Phox) activity in macrophages. We are able to visualize tissue inflammation resulting from wound healing, bacterial infection, foreign substance implantation, and antitumor immune responses. Given the central role of inflammation in a variety of disorders, we believe these noninvasive imaging methods can help dissect the differential roles of neutrophils and macrophages in a variety of pathological conditions.