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

Lee, Jun-Kyoung; Lee, So‐Young; Choi, Young‐Ae; Jin, Meiling; Kim, Yeon-Yong; Kang, Byeong‐Cheol; Kim, Min-Jong; Dhakal, Hima; Lee, Sang-Rae; Kim, Sun-Uk; Khang, Dongwoo; Kim, Sang-Hyun

doi:10.1007/s13273-018-0019-z

Cited by 13 publications

(12 citation statements)

References 42 publications

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“…This process results in the production of multiple proinflammatory cytokines, leading to endoplasmic reticulum (ER)-stress, cellular injury and tissue inflammation. Four in vitro studies [ 111 , 128 , 159 , 160 ] investigated mast cell-mediated allergic inflammation as well as allergy/anaphylaxis-models and concluded that the respective PFAS tested aggravated IgE-dependent allergic symptoms. They all show an increase in intracellular Ca 2+ levels in mast-like cells (mostly rat, but also human cells) after treatment with PFOA [ 128 , 159 ], PFOS [ 160 ], PFDA and PFUnDA, but not PFNA and PFHpA [ 111 ].…”

Section: Resultsmentioning

confidence: 99%

“…Four in vitro studies [ 111 , 128 , 159 , 160 ] investigated mast cell-mediated allergic inflammation as well as allergy/anaphylaxis-models and concluded that the respective PFAS tested aggravated IgE-dependent allergic symptoms. They all show an increase in intracellular Ca 2+ levels in mast-like cells (mostly rat, but also human cells) after treatment with PFOA [ 128 , 159 ], PFOS [ 160 ], PFDA and PFUnDA, but not PFNA and PFHpA [ 111 ]. The authors of the latter study therefore conclude that carbon chain length of PFAS may serve as a factor in allergic inflammation.…”

Section: Resultsmentioning

confidence: 99%

“…In addition to the evidence reviewed by the NTP [ 8 ], our literature review (see Methods ) identified five more recent (2018 and newer) studies. Several in vivo studies address the possible effects of PFAS on hypersensitivity reactions [ 111 , 160 , 184 – 187 ]. For study designs, please see Table 6 in Appendix [ 111 , 160 ] and Table 7 in Appendix [ 184 – 187 ].…”

Section: Resultsmentioning

confidence: 99%

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Consideration of pathways for immunotoxicity of per- and polyfluoroalkyl substances (PFAS)

et al. 2023

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Background Per- and polyfluoroalkyl substances (PFAS) are of public health concern, because of their ubiquitous and extremely persistent occurrence, and depending on their structure, their bio-accumulative, mobile and toxic properties. Human health effects associated with exposure to PFAS include adverse effects on the immune system. In 2020, EFSA (the European Food Safety Authority) defined adverse effects on the immune system as the most critical effect for human health risk assessment, based on reduced antibody responses to childhood vaccines and similar effects observed in experimental animal studies. Likewise, the U.S. EPA (Environmental Protection Agency) considers PFAS-induced immunotoxicity, especially in children, as the critical effect for risk assessment. However, the mechanisms by which antibody concentrations are impacted are not completely understood. Furthermore, other targets of the immune system functions have been reported in the literature. Objective The aim of this review is to explore PFAS-associated immune-related effects. This includes, relevant mechanisms that may underlie the observed effects on the immune system, immunosuppression as well as immunoenhancement, such as i) modulation of cell signalling and nuclear receptors, such as NF-κB and PPARs; ii) alteration of calcium signalling and homoeostasis in immune cells; iii) modulation of immune cell populations; iv) oxidative stress and v) impact on fatty acid metabolism & secondary effects on the immune system. Methods A literature research was conducted using three databases (Web of Science, PubMed, and Scopus), which were searched in July 2021 for relevant studies published in the time frame from 2018 to 2021. In total, 487 publications were identified as potentially eligible and following expert-based judgement, articles relevant for mechanisms of PFAS induced immunotoxicity are discussed. Conclusions Taken together, we show that there is substantial evidence from both in vitro and in vivo experimental as well as epidemiological studies, supporting that various PFAS, not only PFOA and PFOS, affect multiple aspects of the immune system. Timing of exposure is critical, because the developing immune system is especially vulnerable to toxic insults, resulting in a higher risk of particularly adverse immune effects but also other organs later in life.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Consideration of pathways for immunotoxicity of per- and polyfluoroalkyl substances (PFAS)

et al. 2023

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“…Lee et al. () investigated the effect of PFOS exposure on allergic inflammation in ICR mice in an ovalbumin model. Sensitised mice, 6 weeks of age, were intraperitoneally sensitised to ovalbumin with adjuvant on day 0 and 7.…”

Section: Assessmentmentioning

confidence: 99%

“…This effect was not observed using F1 mice from an AhRf/f and a RORc‐cre cross to specifically delete the Ah receptor and it was concluded that this response must be dependent on the Ah receptor. Lee et al. (), using rat basophilic leukaemia cells in vitro , showed that PFOS significantly increased histamine release by IgE stimulated cells, which coincided with enhanced gene expression of proinflammatory cytokines and activation of nuclear NF‐κB. However, even if IgE dependent allergic responses are immune‐related, it is not clear if there is a relation to immune suppression such as evidenced by depressed antibody responses.…”

Section: Assessmentmentioning

confidence: 99%

Risk to human health related to the presence of perfluoroalkyl substances in food

Schrenk¹,

Bignami²,

Bodin³

et al. 2020

EFS2

330

265

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The European Commission asked EFSA for a scientific evaluation on the risks to human health related to the presence of perfluoroalkyl substances ( PFAS s) in food. Based on several similar effects in animals, toxicokinetics and observed concentrations in human blood, the CONTAM Panel decided to perform the assessment for the sum of four PFAS s: PFOA , PFNA , PFH xS and PFOS . These made up half of the lower bound ( LB ) exposure to those PFAS s with available occurrence data, the remaining contribution being primarily from PFAS s with short half‐lives. Equal potencies were assumed for the four PFAS s included in the assessment. The mean LB exposure in adolescents and adult age groups ranged from 3 to 22, the 95th percentile from 9 to 70 ng/kg body weight (bw) per week. Toddlers and ‘other children’ showed a twofold higher exposure. Upper bound exposure was 4‐ to 49‐fold higher than LB levels, but the latter were considered more reliable. ‘Fish meat’, ‘Fruit and fruit products’ and ‘Eggs and egg products’ contributed most to the exposure. Based on available studies in animals and humans, effects on the immune system were considered the most critical for the risk assessment. From a human study, a lowest BMDL 10 of 17.5 ng/ mL for the sum of the four PFAS s in serum was identified for 1‐year‐old children. Using PBPK modelling, this serum level of 17.5 ng/ mL in children was estimated to correspond to long‐term maternal exposure of 0.63 ng/kg bw per day. Since accumulation over time is important, a tolerable weekly intake ( TWI ) of 4.4 ng/kg bw per week was established. This TWI also protects against other potential adverse effects observed in humans. Based on the estimated LB exposure, but also reported serum levels, the CONTAM Panel concluded that parts of the European population exceed this TWI , which is of concern.

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The immunological and oxidative stress regulation of non-thermal plasma-aided water on atopic dermatitis-like lesion in dinitrochlorobenzene-induced SKH-1 hairless mice

Ara

Bajgai

Sajo

et al. 2019

Mol. Cell. Toxicol.

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

Cited by 13 publications

References 42 publications

Consideration of pathways for immunotoxicity of per- and polyfluoroalkyl substances (PFAS)

Consideration of pathways for immunotoxicity of per- and polyfluoroalkyl substances (PFAS)

Risk to human health related to the presence of perfluoroalkyl substances in food

The immunological and oxidative stress regulation of non-thermal plasma-aided water on atopic dermatitis-like lesion in dinitrochlorobenzene-induced SKH-1 hairless mice

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