Development and characterization of an endotoxemia model in zebra fish

Alan Y. Hsu, Theodore Gurol, Tiago J.P. Sobreira, Sheng Zhang, Natalie Moore, Chufan Cai, Zhong-Yin Zhang, Qing Deng

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Endotoxemia is a condition in which endotoxins enter the blood stream and cause systemic and sometimes lethal inflammation. Zebra fish provides a genetically tractable model organism for studying innate immunity, with additional advantages in live imaging and drug discovery. However, a bona fide endotoxemia model has not been established in zebra fish. Here, we have developed an acute endotoxemia model in zebra fish by injecting a single dose of LPS directly into the circulation. Hallmarks of human acute endotoxemia, including systemic inflammation, extensive tissue damage, circulation blockade, immune cell mobilization, and emergency hematopoiesis, were recapitulated in this model. Knocking out the adaptor protein Myd88 inhibited systemic inflammation and improved zebra fish survival. In addition, similar alternations of pathways with human acute endotoxemia were detected using global proteomic profiling and MetaCore™ pathway enrichment analysis. Furthermore, treating zebra fish with a protein tyrosine phosphatase nonreceptor type 11 (Shp2) inhibitor decreased systemic inflammation, immune mobilization, tissue damage, and improved survival in the endotoxemia model. Together, we have established and characterized the phenotypic and gene expression changes of a zebra fish endotoxemia model, which is amenable to genetic and pharmacological discoveries that can ultimately lead to a better mechanistic understanding of the dynamics and interplay of the innate immune system.

Original languageEnglish (US)
Article number607
JournalFrontiers in Immunology
Volume9
Issue numberMAR
DOIs
StatePublished - Mar 29 2018
Externally publishedYes

Fingerprint

Endotoxemia
Zebrafish
Inflammation
Myeloid Differentiation Factor 88
Protein Tyrosine Phosphatases
Hematopoiesis
Drug Discovery
Innate Immunity
Endotoxins
Proteomics
Immune System
Emergencies
Pharmacology
Gene Expression
Survival

Keywords

  • Endotoxemia
  • Endotoxin
  • Inflammation
  • Innate immunity
  • Lipopolysaccharide
  • Zebra fish

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Hsu, A. Y., Gurol, T., Sobreira, T. J. P., Zhang, S., Moore, N., Cai, C., ... Deng, Q. (2018). Development and characterization of an endotoxemia model in zebra fish. Frontiers in Immunology, 9(MAR), [607]. https://doi.org/10.3389/fimmu.2018.00607

Development and characterization of an endotoxemia model in zebra fish. / Hsu, Alan Y.; Gurol, Theodore; Sobreira, Tiago J.P.; Zhang, Sheng; Moore, Natalie; Cai, Chufan; Zhang, Zhong-Yin; Deng, Qing.

In: Frontiers in Immunology, Vol. 9, No. MAR, 607, 29.03.2018.

Research output: Contribution to journalArticle

Hsu, AY, Gurol, T, Sobreira, TJP, Zhang, S, Moore, N, Cai, C, Zhang, Z-Y & Deng, Q 2018, 'Development and characterization of an endotoxemia model in zebra fish', Frontiers in Immunology, vol. 9, no. MAR, 607. https://doi.org/10.3389/fimmu.2018.00607
Hsu AY, Gurol T, Sobreira TJP, Zhang S, Moore N, Cai C et al. Development and characterization of an endotoxemia model in zebra fish. Frontiers in Immunology. 2018 Mar 29;9(MAR). 607. https://doi.org/10.3389/fimmu.2018.00607
Hsu, Alan Y. ; Gurol, Theodore ; Sobreira, Tiago J.P. ; Zhang, Sheng ; Moore, Natalie ; Cai, Chufan ; Zhang, Zhong-Yin ; Deng, Qing. / Development and characterization of an endotoxemia model in zebra fish. In: Frontiers in Immunology. 2018 ; Vol. 9, No. MAR.
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