Molecular & Cellular Toxicology

, Volume 14, Issue 2, pp 173–181 | Cite as

Perfluorooctane sulfonate exacerbates mast cell-mediated allergic inflammation by the release of histamine

  • Jun-Kyoung Lee
  • Soyoung Lee
  • Young-Ae Choi
  • Meiling Jin
  • Yeon-Yong Kim
  • Byeong-Cheol Kang
  • Min-Jong Kim
  • Hima Dhakal
  • Sang-Rae Lee
  • Sun-Uk Kim
  • Dongwoo Khang
  • Sang-Hyun Kim
Original Paper



Mast cells play a major role in allergic inflammation by the release of histamine, an important mediator of type I hypersensitivity. Cencerns regarding potential harmful effects of perfluorooctane sulfonate (PFOS) have been raised. Previous studies reported that PFOS causes various adverse effects such as immunotoxicity and neurotoxicity. This report studied whether PFOS affects mast cells-mediated allergic inflammation.


Ovalbumin-induced active systemic anaphylaxis model was used to assess for the type I hypersensitivity. After sensitization, mice were orally administered with PFOS and then allergic symptoms such as hypothermia and increase of serum allergic mediator were measured. In additional, this study investigated whether PFOS deteriorate allergic inflammation in immunoglobulin E-stimulated mast cells.


PFOS aggravated the allergic symptoms such as hypothermia, and increase of serum histamine, tumor necrosis factor-α and immunoglobulin (Ig) E/ G1. PFOS increased the release of histamine and β-hexosaminidase through the up-regulation of intracellular calcium in IgE-stimulated mast cells. PFOS also enhanced the gene expression of pro-inflammatory cytokines by activating nuclear factor-κB.


This study demonstrated that PFOS more intensifies the mast cell-mediated allergic inflammation.


Perfluorooctane sulfonate Allergic inflammation Mast cells Histamine Nuclear factor-κB 


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  1. 1.
    Genuis, S. J., Beesoon, S. & Birkholz, D. Biomonitoring and elimination of perfluorinated compounds and polychlorinated biphenyls through perspiration: blood, urine, and sweat study. ISRN Toxicol 2013, 483832 (2013).PubMedPubMedCentralGoogle Scholar
  2. 2.
    Tian, H., Gao, J., Li, H., Boyd, S. A. & Gu, C. Complete defluorination of perfluorinated compounds by hydrated electrons generated from 3-indole-acetic-acid in organomodified montmorillonite. Sci Rep 6, 32949 (2016).CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Olsen, G. W. et al. Half-life of serum elimination of perfluorooctanesulfonate,perfluorohexanesulfonate, and perfluorooctanoate in retired fluorochemical production workers. Environ Health Perspect 115, 1298–1305 (2007).CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Harada, K. H. & Koizumi, A. Environmental and biological monitoring of persistent fluorinated compounds in Japan and their toxicities. Environ Health Prev Med 14, 7–19 (2009).CrossRefPubMedGoogle Scholar
  5. 5.
    Granum, B. et al. Pre-natal exposure to perfluoroalkyl substances may be associated with altered vaccine antibody levels and immune-related health outcomes in early childhood. J Immunotoxicol 10, 373–379 (2013).CrossRefPubMedGoogle Scholar
  6. 6.
    Austin, M. E. et al. Neuroendocrine effects of perfluorooctane sulfonate in rats. Environ Health Perspect 111, 1485–1489 (2003).CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Florentin, A., Deblonde, T., Diguio, N., Hautemaniere, A. & Hartemann, P. Impacts of two perfluorinated compounds (PFOS and PFOA) on human hepatoma cells: cytotoxicity but no genotoxicity? Int J Hyg Environ Health 214, 493–499 (2011).CrossRefPubMedGoogle Scholar
  8. 8.
    Hainsworth, T. Raising awareness of the rise in allergy-related conditions. Nurs Times 99, 22–23 (2003).PubMedGoogle Scholar
  9. 9.
    Amin, K. The role of mast cells in allergic inflammation. Respir Med 106, 9–14 (2012).CrossRefPubMedGoogle Scholar
  10. 10.
    Castle, J. D., Guo, Z. & Liu, L. Function of the t-SNARE SNAP-23 and secretory carrier membrane proteins (SCAMPs) in exocytosis in mast cells. Mol Immunol 38, 1337–1340 (2002).CrossRefPubMedGoogle Scholar
  11. 11.
    Gwack, Y., Feske, S., Srikanth, S., Hogan, P. G. & Rao, A. Signalling to transcription: store-operated Ca2+ entry and NFAT activation in lymphocytes. Cell Calcium 42, 145–156 (2007).CrossRefPubMedGoogle Scholar
  12. 12.
    Boyce, J. A. Mast cells: beyond IgE. J Allergy Clin Immunol 111, 24–32 (2003).CrossRefPubMedGoogle Scholar
  13. 13.
    Rivera, J. & Gilfillan, A. M. Molecular regulation of mast cell activation. J Allergy Clin Immunol 117, 1214–1225 (2006).CrossRefPubMedGoogle Scholar
  14. 14.
    Singh, T. S., Lee, S., Kim, H. H., Choi, J. K. & Kim, S. H. Perfluorooctanoic acid induces mast cell-mediated allergic inflammation by the release of histamine and inflammatory mediators. Toxicol Lett 210, 64–70 (2012).CrossRefPubMedGoogle Scholar
  15. 15.
    Yamaki, K. & Yoshino, S. Enhancement of Fcepsilon-RI-mediated degranulation response in the rat basophilic leukemia cell line RBL-2H3 by the fluorosurfactants perfluorooctanoic acid and perfluorooctane sulfonate. Environ Toxicol Pharmacol 29, 183–189 (2010).CrossRefPubMedGoogle Scholar
  16. 16.
    Je, I. G. et al. Tyrosol suppresses allergic inflammation by inhibiting the activation of phosphoinositide 3-kinase in mast cells. PLoS One 10, e0129829 (2015).CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Je, I. G. et al. SG-HQ2 inhibits mast cell-mediated allergic inflammation through suppression of histamine release and pro-inflammatory cytokines. Exp Biol Med (Maywood) 240, 631–638 (2015).CrossRefGoogle Scholar
  18. 18.
    Bae, Y., Lee, S. & Kim, S. H. Chrysin suppresses mast cell-mediated allergic inflammation: involvement of calcium, caspase-1 and nuclear factor-kappaB. Toxicol Appl Pharmacol 254, 56–64 (2011).CrossRefPubMedGoogle Scholar
  19. 19.
    Yoon, S. Y. et al. 1-palmitoyl-2-linoleoyl-3-acetyl-racglycerol (EC-18) modulates Th2 immunity through attenuation of IL-4 expression. Immune Netw 15, 100–109 (2015).CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Finkelman, F. D., Rothenberg, M. E., Brandt, E. B., Morris, S. C. & Strait, R. T. Molecular mechanisms of anaphylaxis: lessons from studies with murine models. J Allergy Clin Immunol 115, 449–457 (2005).CrossRefPubMedGoogle Scholar
  21. 21.
    Galli, S. J. & Tsai, M. IgE and mast cells in allergic disease. Nat Med 18, 693–704 (2012).CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Tak, P. P. & Firestein, G. S. NF-kappaB: a key role in inflammatory diseases. J Clin Invest 107, 7–11 (2001).CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Post, G. B., Cohn, P. D. & Cooper, K. R. Perfluorooctanoic acid (PFOA), an emerging drinking water contaminant: a critical review of recent literature. Environ Res 116, 93–117 (2012).CrossRefPubMedGoogle Scholar
  24. 24.
    Loccisano, A. E., Longnecker, M. P., Campbell, J. L., Jr., Andersen, M. E. & Clewell, H. J., 3rd. Development of PBPK models for PFOA and PFOS for human pregnancy and lactation life stages. J Toxicol Environ Health A 76, 25–57 (2013).CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Tonnelier, A., Coecke, S. & Zaldivar, J. M. Screening of chemicals for human bioaccumulative potential with a physiologically based toxicokinetic model. Arch Toxicol 86, 393–403 (2012).CrossRefPubMedGoogle Scholar
  26. 26.
    Kannan, K. et al. Perfluorinated compounds in aquatic organisms at various trophic levels in a Great Lakes food chain. Arch Environ Contam Toxicol 48, 559–566 (2005).CrossRefPubMedGoogle Scholar
  27. 27.
    D’Hollander, W., de Voogt, P., De Coen, W. & Bervoets, L. Perfluorinated substances in human food and other sources of human exposure. Rev Environ Contam Toxicol 208, 179–215 (2010).PubMedGoogle Scholar
  28. 28.
    Fromme, H., Tittlemier, S. A., Volkel, W., Wilhelm, M. & Twardella, D. Perfluorinated compounds-exposure assessment for the general population in Western countries. Int J Hyg Environ Health 212, 239–270 (2009).CrossRefPubMedGoogle Scholar
  29. 29.
    Trudel, D. et al. Estimating consumer exposure to PFOS and PFOA. Risk Anal 28, 251–269 (2008).CrossRefPubMedGoogle Scholar
  30. 30.
    Kudo, N. & Kawashima, Y. Toxicity and toxicokinetics of perfluorooctanoic acid in humans and animals. J Toxicol Sci 28, 49–57 (2003).CrossRefPubMedGoogle Scholar
  31. 31.
    Qazi, M. R. et al. The atrophy and changes in the cellular compositions of the thymus and spleen observed in mice subjected to short-term exposure to perfluorooctanesulfonate are high-dose phenomena mediated in part by peroxisome proliferator-activated receptor-alpha. Toxicology 260, 68–76 (2009).CrossRefPubMedGoogle Scholar
  32. 32.
    EFSA. Opinion of the scientific panel on contaminants in the food chain on perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA) and their salts. The EFSA Journal 653, 1–131 (2008).Google Scholar
  33. 33.
    ATSDR. in Atlanta: U.S. Department of Health and Human Services (2015).Google Scholar
  34. 34.
    Haug, L. S., Huber, S., Becher, G. & Thomsen, C. Characterisation of human exposure pathways to perfluorinated compounds-comparing exposure estimates with biomarkers of exposure. Environ Int 37, 687–693 (2011).CrossRefPubMedGoogle Scholar
  35. 35.
    Kennedy, G. L., Jr. et al. The toxicology of perfluorooctanoate. Crit Rev Toxicol 34, 351–384 (2004).CrossRefPubMedGoogle Scholar
  36. 36.
    Sampson, H. A. et al. Second symposium on the definition and management of anaphylaxis: summary report-second National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network symposium. Ann Emerg Med 47, 373–380 (2006).CrossRefPubMedGoogle Scholar
  37. 37.
    He, S. H., Zhang, H. Y., Zeng, X. N., Chen, D. & Yang, P. C. Mast cells and basophils are essential for allergies: mechanisms of allergic inflammation and a proposed procedure for diagnosis. Acta Pharmacol Sin 34, 1270–1283 (2013).CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Wex, E., Thaler, E., Blum, S. & Lamb, D. A novel model of IgE-mediated passive pulmonary anaphylaxis in rats. PLoS One 9, e116166 (2014).CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Osterfeld, H. et al. Differential roles for the IL-9/IL-9 receptor alpha-chain pathway in systemic and oral antigen-induced anaphylaxis. J Allergy Clin Immunol 125, 469–476 e462 (2010).CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Ahrens, R. et al. Intestinal mast cell levels control severity of oral antigen-induced anaphylaxis in mice. Am J Pathol 180, 1535–1546 (2012).CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Ishikawa, R. et al. IgG-mediated systemic anaphylaxis to protein antigen can be induced even under conditions of limited amounts of antibody and antigen. Biochem Biophys Res Commun 402, 742–746 (2010).CrossRefPubMedGoogle Scholar
  42. 42.
    Devey, L., Festing, M. F. & Wigmore, S. J. Effect of temperature control upon a mouse model of partial hepatic ischaemia/reperfusion injury. Lab Anim 42, 12–18 (2008).CrossRefPubMedGoogle Scholar
  43. 43.
    Laidlaw, T. M. et al. Characterization of a novel human mast cell line that responds to stem cell factor and expresses functional FcepsilonRI. J Allergy Clin Immunol 127, 815–822 e811-815 (2011).CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Nishida, K. et al. Fc{epsilon}RI-mediated mast cell degranulation requires calcium-independent microtubule-dependent translocation of granules to the plasma membrane. J Cell Biol 170, 115–126 (2005).CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Suzuki, Y. et al. Fc epsilon RI signaling of mast cells activates intracellular production of hydrogen peroxide: role in the regulation of calcium signals. J Immunol 171, 6119–6127 (2003).CrossRefPubMedGoogle Scholar
  46. 46.
    Woolley, D. E. & Tetlow, L. C. Mast cell activation and its relation to proinflammatory cytokine production in the rheumatoid lesion. Arthritis Res 2, 65–74 (2000).CrossRefPubMedGoogle Scholar
  47. 47.
    DeWitt, J. C., Peden-Adams, M. M., Keller, J. M. & Germolec, D. R. Immunotoxicity of perfluorinated compounds: recent developments. Toxicol Pathol 40, 300–311 (2012).CrossRefPubMedGoogle Scholar

Copyright information

© The Korean Society of Toxicogenomics and Toxicoproteomics and Springer Science+Business Media B.V., part of Springer Nature 2018

Authors and Affiliations

  • Jun-Kyoung Lee
    • 1
  • Soyoung Lee
    • 1
    • 2
  • Young-Ae Choi
    • 1
  • Meiling Jin
    • 1
  • Yeon-Yong Kim
    • 1
  • Byeong-Cheol Kang
    • 1
  • Min-Jong Kim
    • 1
  • Hima Dhakal
    • 1
  • Sang-Rae Lee
    • 3
  • Sun-Uk Kim
    • 3
  • Dongwoo Khang
    • 4
  • Sang-Hyun Kim
    • 1
  1. 1.Cell and Matrix Research Institute, Department of Pharmacology, School of MedicineKyungpook National UniversityDaeguRepublic of Korea
  2. 2.Immunoregulatory Materials Research CenterKorea Research Institute of Bioscience and BiotechnologyJeongeupRepublic of Korea
  3. 3.National Primate Research CenterKorea Research Institute of Bioscience and BiotechnologyOchangRepublic of Korea
  4. 4.Department of Physiology, School of MedicineGachon UniversityIncheonRepublic of Korea

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