Live imaging of leukocyte recruitment in a zebrafish model of chemical liver injury

Stoddard, Michelina and Huang, Cong and Enyedi, Balázs and Niethammer, Philipp (2019) Live imaging of leukocyte recruitment in a zebrafish model of chemical liver injury. SCIENTIFIC REPORTS, 9 (1). No. 28. ISSN 2045-2322

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Abstract

Studying early immune responses to organ damage in situ requires animal models amenable to intravital imaging. Here, we used transparent zebrafish larvae, a powerful animal model for innate immunity, to measure leukocyte recruitment to damaged livers. Bath application of metronidazole (Mtz) to fish expressing nitroreductase (NTR) under a liver-specific promoter damaged the organ within 24 hours causing oxidative stress, distorted liver morphology, accumulation of TUNEL-positive cells, and transcriptional upregulation of apoptotic and antioxidant genes. Inflammatory gene transcription in damaged hepatocytes was attenuated. In line with predominant apoptosis, macrophages were massively recruited into Mtz/NTR-damaged livers. By contrast, neutrophil infiltration was more variable and delayed, consistent with less abundant necrosis and an attenuated inflammatory capacity of damaged hepatocytes.

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