PUBLICATION

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

Authors
Stoddard, M., Huang, C., Enyedi, B., Niethammer, P.
ID
ZDB-PUB-190113-15
Date
2019
Source
Scientific Reports   9: 28 (Journal)
Registered Authors
Enyedi, Balázs, Huang, Cong, Niethammer, Philipp
Keywords
none
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • Anti-Infective Agents/administration & dosage
  • Anti-Infective Agents/adverse effects
  • Chemical and Drug Induced Liver Injury/pathology*
  • Disease Models, Animal
  • Gene Expression
  • Immunity, Innate*
  • Intravital Microscopy/methods*
  • Leukocytes/immunology*
  • Metronidazole/administration & dosage
  • Metronidazole/adverse effects
  • Nitroreductases/metabolism
  • Oxidative Stress
  • Recombinant Proteins/metabolism
  • Zebrafish
PubMed
30631093 Full text @ Sci. Rep.
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.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping