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

Sci Rep. 2019 Jan 10;9(1):28. doi: 10.1038/s41598-018-36771-9.

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.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

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

Substances

  • Anti-Infective Agents
  • Recombinant Proteins
  • Metronidazole
  • Nitroreductases