PUBLICATION

Development and Characterization of an Endotoxemia Model in Zebra Fish

Authors

Hsu, A.Y., Gurol, T., Sobreira, T.J.P., Zhang, S., Moore, N., Cai, C., Zhang, Z.Y., Deng, Q.

ID

ZDB-PUB-180418-33

Date

2018

Source

Frontiers in immunology 9: 607 (Journal)

Registered Authors

Deng, Qing, Gurol, Theodore, Hsu, Alan

Keywords

endotoxemia, endotoxin, inflammation, innate immunity, lipopolysaccharide, zebra fish

MeSH Terms

Zebrafish/immunology*
Gene Expression Profiling
Disease Models, Animal*
Humans
Cell Movement
Immunity, Innate*
Blood Circulation
Cells, Cultured
Signal Transduction
Fish Proteins/antagonists & inhibitors
Myeloid Differentiation Factor 88/antagonists & inhibitors
Lipopolysaccharides/administration & dosage
Hematopoiesis
Endotoxemia/immunology*
Immunity, Cellular
Animals
Inflammation/immunology*
Protein Tyrosine Phosphatase, Non-Receptor Type 11/antagonists & inhibitors

(all 18)

PubMed

29651289 Full text @ Front Immunol

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.

Genes / Markers

Figures

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Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
c3a.1	WT	chemical treatment by injection: lipopolysaccharide	Protruding-mouth	whole organism	RTPCR	Fig. 2
c3a.1	WT	chemical treatment by injection: lipopolysaccharide	Protruding-mouth	whole organism	RTPCR	Fig. 7
c3a.1	WT	chemical treatment by injection: EC 3.1.3.48 (protein-tyrosine-phosphatase) inhibitor, chemical treatment by injection: lipopolysaccharide	Protruding-mouth	whole organism	RTPCR	Fig. 7
c3a.1	WT	control	Protruding-mouth	whole organism	RTPCR	Fig. 2
cdh5	WT	chemical treatment by injection: EC 3.1.3.48 (protein-tyrosine-phosphatase) inhibitor, chemical treatment by injection: lipopolysaccharide	Protruding-mouth	whole organism	RTPCR	Fig. 7
cdh5	WT	chemical treatment by injection: lipopolysaccharide	Protruding-mouth	whole organism	RTPCR	Fig. 7
cdh5	WT	chemical treatment by injection: lipopolysaccharide	Protruding-mouth	whole organism	RTPCR	Fig. 3
cdh5	WT	control	Protruding-mouth	whole organism	RTPCR	Fig. 3
cdh5	WT	control	Day 4	whole organism	RTPCR	Fig. 3
cdh5	WT	chemical treatment by injection: lipopolysaccharide	Day 4	whole organism	RTPCR	Fig. 3

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
WT	chemical treatment by injection: lipopolysaccharide	Protruding-mouth	blood circulation decreased efficacy, abnormal	Fig. 1
WT	chemical treatment by injection: lipopolysaccharide	Protruding-mouth	pericardial region edematous, abnormal	Fig. 1
WT	chemical treatment by injection: lipopolysaccharide	Protruding-mouth	whole organism c3a.1 expression increased amount, abnormal	Fig. 2
WT	chemical treatment by injection: lipopolysaccharide	Protruding-mouth	whole organism cdh5 expression amount, ameliorated	Fig. 3
WT	chemical treatment by injection: lipopolysaccharide	Protruding-mouth	whole organism cldn2 expression increased amount, abnormal	Fig. 3
WT	chemical treatment by injection: lipopolysaccharide	Protruding-mouth	whole organism cldn5a expression decreased amount, abnormal	Fig. 3
WT	chemical treatment by injection: lipopolysaccharide	Protruding-mouth	whole organism cldn5b expression decreased amount, abnormal	Fig. 3
WT	chemical treatment by injection: lipopolysaccharide	Protruding-mouth	whole organism csf1b expression increased amount, abnormal	Fig. 4
WT	chemical treatment by injection: lipopolysaccharide	Protruding-mouth	whole organism csf3a expression increased amount, abnormal	Fig. 4
WT	chemical treatment by injection: lipopolysaccharide	Protruding-mouth	whole organism cxcl8a expression increased amount, abnormal	Fig. 2

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Mutations / Transgenics

Allele	Construct	Type
gl22Tg	Tg(mpeg1:EGFP)	Transgenic Insertion
nc1Tg	Tg(6xHsa.NFKB:EGFP)	Transgenic Insertion
pu17Tg	Tg(actb2:SEC-Hsa.ANXA5-YFP)	Transgenic Insertion
uwm7Tg	Tg(mpx:mCherry)	Transgenic Insertion

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Human Disease / Model

Human Disease	Fish	Conditions	Evidence
bacterial sepsis	WT	chemical treatment by injection: lipopolysaccharide	TAS

Sequence Targeting Reagents

Target	Reagent	Reagent Type
myd88	CRISPR7-myd88	CRISPR
myd88	CRISPR8-myd88	CRISPR

Fish

Fish
gl22Tg; uwm7Tg
nc1Tg
nc1Tg + CRISPR7-myd88 + CRISPR8-myd88
pu17Tg
WT

Antibodies

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
EGFP	EFG	EGFP
mCherry	EFG	mCherry
YFP	EFG	YFP

Mapping

Hsu et al., 2018 ZDB-PUB-180418-33 PMID:29651289

Development and Characterization of an Endotoxemia Model in Zebra Fish

Hsu et al., 2018

ZDB-PUB-180418-33
PMID:29651289