Persistent alterations in immune cell populations and function from a single dose of perfluorononanoic acid (PFNA) in C57Bl/6 mice

• Published in: Food and chemical toxicology 2017-02, Vol.100, p.24-33
• Main Authors: Rockwell, Cheryl E., Turley, Alexandra E., Cheng, Xingguo, Fields, Patrick E., Klaassen, Curtis D.
• Format: Article
• Language: English
• Subjects: Animals; B cell; Dose-Response Relationship, Drug; Enzyme-Linked Immunosorbent Assay; Fatty Acids; Female; Flow Cytometry; Fluorocarbons - administration & dosage; Fluorocarbons - pharmacology; Immune System - drug effects; Immune System - immunology; LPS; Male; Mice; Mice, Inbred C57BL; Organ Size - drug effects; Perfluoroalkyl substance (PFAS); Perfluorononanoic acid (PFNA); Spleen - drug effects; T cell; Thymocytes - drug effects; TNFα
• ISSN: 0278-6915; 1873-6351; 1873-6351
• DOI: 10.1016/j.fct.2016.12.004

Perfluorononanoic acid (PFNA) is a perfluoroalkyl substance (PFAS) that is structurally related to perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS). Whereas PFOA and PFOS are known immunotoxicants, PFNA is less well characterized. Our previous study showed that PFNA has immunomodulatory effects on leukocyte populations and immune function. The present studies sought to determine whether, and to what degree, the immune system recovered 28 days after PFNA exposure. None of the parameters measured had fully recovered. A few parameters had partially recovered, including decreased spleen size and the decreased ratio of the CD4+/CD8+ double-positive population in thymus. The majority of effects of PFNA remained unchanged 28 days after exposure, including decreased proportion of intact thymocytes (as determined by FSC vs SSC), alterations in the ratios of immune cell populations in spleen and the CD4+, CD8+ and double-negative populations in thymus. Notably, PFNA markedly increased the TNFα response to LPS in vivo, and no recovery was evident 28 days after exposure. The effect of PFNA on CD4+ T cells, CD8+ T cells and CD19+ cells was more pronounced in females. The current study demonstrates that a single high dose exposure to PFNA (e.g. as might occur accidentally in an occupational setting) has long-lasting effects on the immune system. •No immune parameters had fully recovered 4 weeks after PFNA exposure.•PFNA decreased spleen and thymus size.•PFNA altered immune cell ratios in spleen and thymus.•Effect of PFNA on immune cell ratios was more pronounced in females.•PFNA markedly increased the TNFa response to LPS in vivo.