Flow Cytometry for the Immunotoxicologist

Espenschied, Scott T.; Tighe, Robert; Gowdy, Kymberly M.

doi:10.1007/978-1-4939-8549-4_12

Cited by 2 publications

(1 citation statement)

References 53 publications

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“…Although zebrafish are an exceptional model for toxicity studies, they have been widely neglected as a model for immunotoxicity (Planchart et al 2016;Espenschied et al 2018). As teleost fish, they possess both an innate immune system and an adaptive immune system capable of defending the host from pathogens, and all major immune cell lineages and pathways in zebrafish are conserved in mammalian models (reviewed in Stachura and Traver 2016;Traver and Yoder 2020).…”

Section: Introductionmentioning

confidence: 99%

In vivoassessment of respiratory burst inhibition by xenobiotic exposure using larval zebrafish

Phelps

Fletcher

Rodríguez-Nunez

et al. 2020

Journal of Immunotoxicology

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Currently, assessment of the potential immunotoxicity of a given agent involves a tiered approach for hazard identification and mechanistic studies, including observational studies, evaluation of immune function, and measurement of susceptibility to infectious and neoplastic diseases. These studies generally use costly low-throughput mammalian models. Zebrafish, however, offer an excellent alternative due to their rapid development, ease of maintenance, and homology to mammalian immune system function and development. Larval zebrafish also are a convenient model to study the innate immune system with no interference from the adaptive immune system. In this study, a respiratory burst assay (RBA) was utilized to measure reactive oxygen species (ROS) production after developmental xenobiotic exposure. Embryos were exposed to non-teratogenic doses of chemicals and at 96 h post-fertilization, the ability to produce ROS was measured. Using the RBA, 12 compounds with varying immune-suppressive properties were screened. Seven compounds neither suppressed nor enhanced the respiratory burst; five reproducibly suppressed global ROS production, but with varying potencies: benzo[a]pyrene, 17b-estradiol, lead acetate, methoxychlor, and phenanthrene. These five compounds have all previously been reported as immunosuppressive in mammalian innate immunity assays. To evaluate whether the suppression of ROS by these compounds was a result of decreased immune cell numbers, flow cytometry with transgenic zebrafish larvae was used to count the numbers of neutrophils and macrophages after chemical exposure. With this assay, benzo[a]pyrene was found to be the only chemical that induced a change in the number of immune cells by increasing macrophage but not neutrophil numbers. Taken together, this work demonstrates the utility of zebrafish larvae as a vertebrate model for identifying compounds that impact innate immune function at non-teratogenic levels and validates measuring ROS production and phagocyte numbers as metrics for monitoring how xenobiotic exposure alters the innate immune system.

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Section: Introductionmentioning

confidence: 99%

In vivoassessment of respiratory burst inhibition by xenobiotic exposure using larval zebrafish

Phelps

Fletcher

Rodríguez-Nunez

et al. 2020

Journal of Immunotoxicology

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Évaluation de l’immunotoxicité en recherche et dans le cadre du développement biomédical

Nguyen

Jordheim

2022

Biologie Aujourd’hui

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L’immunotoxicologie est l’étude des effets toxiques de toute substance sur le système immunitaire et ses fonctions. Dans les différents domaines d’application, cette science est cadrée par divers textes réglementaires et lignes directrices. Les études sont basées sur des techniques in vitro, ex vivo et in vivo et sont observationnelles ou fonctionnelles, permettant respectivement de démontrer un effet et de décrire les mécanismes en jeu. Dans cette revue, nous présentons les différents tests à effectuer dans le domaine biomédical, avec une attention particulière au test d’évaluation de la réponse thymo-dépendante (TDAR). Nous discutons également brièvement des évolutions à suivre dans ce domaine cherchant entre autres une approche plus éthique comme la limitation de l’utilisation des animaux de laboratoire. Ces évolutions sont notamment représentées par le développement de modèles cellulaires pertinents.

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Flow Cytometry for the Immunotoxicologist

Cited by 2 publications

References 53 publications

In vivoassessment of respiratory burst inhibition by xenobiotic exposure using larval zebrafish

In vivoassessment of respiratory burst inhibition by xenobiotic exposure using larval zebrafish

Évaluation de l’immunotoxicité en recherche et dans le cadre du développement biomédical

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