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

TitleLive imaging of leukocyte recruitment in a zebrafish model of chemical liver injury.
Publication TypeJournal Article
Year of Publication2019
AuthorsStoddard M, Huang C, Enyedi B, Niethammer P
JournalSci Rep
Volume9
Issue1
Pagination28
Date Published2019 01 10
ISSN2045-2322
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.

DOI10.1038/s41598-018-36771-9
Alternate JournalSci Rep
PubMed ID30631093
PubMed Central IDPMC6328554
Grant ListP30 CA008748 / CA / NCI NIH HHS / United States
R01 GM099970 / GM / NIGMS NIH HHS / United States
T32 GM007739 / GM / NIGMS NIH HHS / United States