A high-throughput chemically induced inflammation assay in zebrafish
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Archivos
Fecha
2010-12-22
Profesor/a Guía
Facultad/escuela
Idioma
en
Título de la revista
ISSN de la revista
Título del volumen
Editor
BMC
Nombre de Curso
Licencia CC
CC BY 2.0
ATTRIBUTION 2.0 GENERIC
Deed
Licencia CC
https://creativecommons.org/licenses/by/2.0/
Resumen
Background: Studies on innate immunity have benefited from the introduction of zebrafish as a model system. Transgenic fish expressing fluorescent proteins in leukocyte populations allow direct, quantitative visualization of an inflammatory response in vivo. It has been proposed that this animal model can be used for high-throughput screens aimed at the identification of novel immunomodulatory lead compounds. However, current assays require invasive manipulation of fish individually, thus preventing high-content screening.Results: Here we show that specific, noninvasive damage to lateral line neuromast cells can induce a robust acute inflammatory response. Exposure of fish larvae to sublethal concentrations of copper sulfate selectively damages the sensory hair cell population inducing infiltration of leukocytes to neuromasts within 20 minutes. Inflammation can be assayed in real time using transgenic fish expressing fluorescent proteins in leukocytes or by histochemical assays in fixed larvae. We demonstrate the usefulness of this method for chemical and genetic screens to detect the effect of immunomodulatory compounds and mutations affecting the leukocyte response. Moreover, we transformed the assay into a high-throughput screening method by using a customized automated imaging and processing system that quantifies the magnitude of the inflammatory reaction.Conclusions: This approach allows rapid screening of thousands of compounds or mutagenized zebrafish for effects on inflammation and enables the identification of novel players in the regulation of innate immunity and potential lead compounds toward new immunomodulatory therapies. We have called this method the chemically induced inflammation assay, or ChIn assay.See Commentary article: http://www.biomedcentral.com/1741-7007/8/148. © 2010 d'Alençon et al; licensee BioMed Central Ltd.
Notas
INDEXACIÓN: SCOPUS.
Palabras clave
Animals, Animals, Genetically Modified, Anti-Inflammatory Agents, Cell Movement, Disease Models, Animal, Drug Evaluation, Preclinical, Embryo, Nonmammalian, High-Throughput Screening Assays, Immunologic Factors, Inflammation, Leukocytes, Models, Biological, Neutrophil Infiltration, Reactive Oxygen Species, Zebrafish
Citación
BMC Biology, Volume 8, 22 December 2010, Article number 151
DOI
10.1186/1741-7007-8-151