Legacy and emerging per- and polyfluoroalkyl substances suppress the neutrophil respiratory burst

• Published in: Journal of immunotoxicology Vol. 20; no. 1; p. 2176953
• Main Authors: Phelps, Drake W., Palekar, Anika I., Conley, Haleigh E., Ferrero, Giuliano, Driggers, Jacob H., Linder, Keith E., Kullman, Seth W., Reif, David M., Sheats, M. Katie, DeWitt, Jamie C., Yoder, Jeffrey A.
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 01.12.2023; Taylor & Francis Ltd; Taylor & Francis Group
• Subjects: Acids; Adaptive immunity; Alkanesulfonic Acids - toxicity; Animals; Danio rerio; Environmental Pollutants; Fluorocarbons - toxicity; Foams; Humans; Immune response; Innate immunity; Leukocytes (neutrophilic); Microbicides; Neutrophils; per- and polyfluoroalkyl substances (PFAS); Perfluoroalkyl & polyfluoroalkyl substances; Perfluorochemicals; Perfluorohexane; Perfluorooctane sulfonic acid; Perfluorooctanoic acid; Reactive Oxygen Species; Respiratory Burst; Zebrafish; Innate immunity; zebrafish; neutrophils; reactive oxygen species; per- and polyfluoroalkyl substances (PFAS)
• ISSN: 1547-691X; 1547-6901; 1547-6901
• DOI: 10.1080/1547691X.2023.2176953

Per- and polyfluoroalkyl substances (PFASs) are used in a multitude of processes and products, including nonstick coatings, food wrappers, and fire-fighting foams. These chemicals are environmentally-persistent, ubiquitous, and can be detected in the serum of 98% of Americans. Despite evidence that PFASs alter adaptive immunity, few studies have investigated their effects on innate immunity. The report here presents results of studies that investigated the impact of nine environmentally-relevant PFASs [e.g. perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid potassium salt (PFOS-K), perfluorononanoic acid (PFNA), perfluorohexanoic acid (PFHxA), perfluorohexane sulfonic acid (PFHxS), perfluorobutane sulfonic acid (PFBS), ammonium perfluoro(2-methyl-3-oxahexanoate) (GenX), 7H-perfluoro-4-methyl-3,6-dioxa-octane sulfonic acid (Nafion byproduct 2), and perfluoromethoxyacetic acid sodium salt (PFMOAA-Na)] on one component of the innate immune response, the neutrophil respiratory burst. The respiratory burst is a key innate immune process by which microbicidal reactive oxygen species (ROS) are rapidly induced by neutrophils in response to pathogens; defects in the respiratory burst can increase susceptibility to infection. The study here utilized larval zebrafish, a human neutrophil-like cell line, and primary human neutrophils to ascertain whether PFAS exposure inhibits ROS production in the respiratory burst. It was observed that exposure to PFHxA and GenX suppresses the respiratory burst in zebrafish larvae and a human neutrophil-like cell line. GenX also suppressed the respiratory burst in primary human neutrophils. This report is the first to demonstrate that these PFASs suppress neutrophil function and support the utility of employing zebrafish larvae and a human cell line as screening tools to identify chemicals that may suppress human immune function.