Exposure to perfluorooctanoic acid (PFOA) decreases neutrophil migration response to injury in zebrafish embryos
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BMC Research Notes Open Access
RESEARCH NOTE
Exposure to perfluorooctanoic acid (PFOA) decreases neutrophil migration response to injury in zebrafish embryos Alison M. Pecquet1, Andrew Maier2, Susan Kasper1, Saulius Sumanas3,4* and Jagjit Yadav1*
Abstract Objective: Perfluorooctanoic acid (PFOA) is a ubiquitous environmental contaminant and a known immune suppressant in humans and experimental animal models. Studies on PFOA have focused on suppression of the adaptive immune response; however, little is known of the impact on innate immunity, especially during embryogenesis. Therefore, we utilized the zebrafish chemotaxis assay coupled with in situ hybridization for myeloperoxidase expression to determine the effects of PFOA exposure on neutrophil migration in the developing zebrafish embryo. Zebrafish embryos are a well-established in vivo model that exhibit high homology with the development of human innate immunity. Results: Treatment of zebrafish with increasing concentrations of PFOA identified the lethal concentration in 50% of the embryos (LC50) to be 300 mg/L. Utilizing the zebrafish chemotaxis assay, this study showed that wounding induced significant neutrophil migration to the site of injury, and that neutrophil number in the wound region was significantly reduced in response to 48-h PFOA exposure (well below doses causing acute mortality). This study demonstrates that the developing embryo is sensitive to PFOA exposure and that PFOA can modify the innate immune system during embryonic development. These results lay the groundwork for future investigation on the mechanisms underlying PFOA-induced developmental immunotoxicity. Keywords: PFOA, Zebrafish, In vivo, Neutrophil, Chemotaxis, Lethal concentration in 50% of embryos (LC50), Immunotoxicity, In situ hybridization, Wounding, Myeloperoxidase Introduction Immunotoxicity from exposure to environmental chemicals is an emerging concern, as the prevalence of human disorders with mechanistic roots in immune function continues to increase [1]. Many xenobiotics appear to modulate the immune system at concentrations well below those tested in traditional toxicology studies, *Correspondence: [email protected]; [email protected] 1 Department of Environmental and Public Health Sciences, University of Cincinnati College of Medicine, 160 Panzeca Way, Cincinnati, OH 45267, USA 3 Division of Developmental Biology, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Ave., Cincinnati, OH 45229, USA Full list of author information is available at the end of the article
possibly contributing to immune-related diseases [1, 2]. Particularly relevant to disease susceptibility is disruption of innate immunity signaling pathways and inflammatory responses, yet the effects of environmental toxicants on innate immunity parameters, especially during early life stages, is not well studied [1]. Perfluorooctanoic acid (PFOA) is ubiquitous in the environment and is detectable and persistent in human serum [3–5]. PFOA was recently “presumed to be an immune ha
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