Noninvasive imaging of the lung NETosis by anti-Ly6G iron oxide nanoparticles

Abstract

It is challenging to visualize noninvasively the formation of neutrophil extracellular traps, known as NETosis, and therefore difficult to monitor disease progression. A desirable molecular imaging probe is the iron oxide nanoparticle (NP) that could induce reactive oxygen species. Here, we used C57BL/6 mice with pristane-induced lupus, which mimics systemic lupus erythematosus. Administration of anti-Ly6G antibody-conjugated NP allowed detection of NETosis with fluorescent molecular imaging, as evidenced by flow cytometric analysis of citrullinated histone H3 expression in lung neutrophils. This finding was consistent with NP-induced blood NETosis in a spontaneous lupus model of B6.MRL-lpr mice. A chronic assessment was performed in which the lupus mice were protected from enhanced oxidative burst by anti-Ly6G NP. This NP can migrate from the peritoneal cavity to the lungs, as visualized by magnetic particle imaging. Overall, our study provides evidence for a highly sensitive assessment of NETosis in lupus through magnetic particle imaging.