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28-Day dietary exposure of mice to a low total dose (7 mg/kg) of perfluorooctanesulfonate (PFOS) alters neither the cellular compositions of the thymus and spleen nor humoral immune responses: Does the route of administration play a pivotal role in PFOS-induced immunotoxicity?
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
2010 (English)In: Toxicology, ISSN 0300-483X, E-ISSN 1879-3185, Vol. 267, no 03-jan, 132-139 p.Article in journal (Refereed) Published
Abstract [en]

Short-term exposure of mice to high doses of perfluorooctanesulfonate (PFOS), an ubiquitous and highly persistent environmental contaminant, induces various metabolic changes and toxic effects, including immunotoxicity. However, extrapolation of these findings to the long-term, low-dose exposures to which humans are subject is highly problematic. In this connection, recent studies have concluded that sub-chronic (28-day) exposure of mice by oral gavage to doses of PFOS that result in serum levels comparable to those found in general human populations suppress adaptive immunity. Because of the potential impact of these findings on environmental research and monitoring, we have examined here whether sub-chronic dietary exposure (a major route of human exposure) to a similarly low-dose of PFOS also suppress adaptive immune responses. Dietary treatment of male B6C3F1 mice for 28 days with a dose of PFOS that resulted in a serum concentration of 11 mu g/ml (ppm) significantly reduced body weight gain and increased liver mass. However, this treatment did not alter the cellular compositions of the thymus and spleen; the number of splenic cells secreting IgM antibodies against sheep red blood cell (SRBC); serum levels of IgM and IgG antibodies specifically towards SRBC; or circulating levels of IgM antibodies against the T-cell-independent antigen trinitrophenyl conjugated to lipopolysaccharide (TNP-LPS). These findings indicate that such sub-chronic dietary exposure of mice to PFOS resulting in serum levels approximately 8-85-fold greater than those observed in occupationally exposed individuals does not exert adverse effects on adaptive immunity.

Place, publisher, year, edition, pages
2010. Vol. 267, no 03-jan, 132-139 p.
Keyword [en]
Humoral immune responses, T-cell-independent antigen, T-cell-dependent antigen, Perfluorooctanesulfonate (PFOS)
National Category
Pharmaceutical Sciences
URN: urn:nbn:se:su:diva-50059DOI: 10.1016/j.tox.2009.10.035ISI: 000274588700017OAI: diva2:382746

authorCount :4

Available from: 2011-01-03 Created: 2010-12-21 Last updated: 2012-12-07Bibliographically approved
In thesis
1. Immunohepatotoxicity of the persistent environmental pollutants perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS)
Open this publication in new window or tab >>Immunohepatotoxicity of the persistent environmental pollutants perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS)
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS), manufactured for a variety of industrial and consumer applications, are ubiquitous environmental pollutants. Their accumulation in humans and wildlife raises serious health concerns.

Here, we examined the potential effects of PFOA and PFOS on the innate immune system in mice. Short-term dietary exposure to high doses reduces the total number and subpopulations of circulating white blood cells. Moreover, production of proinflammatory cytokines by macrophages in the peritoneal cavity and bone marrow, but not in the spleen following exposure to in vitro or in vivo stimulation by bacterial lipopolysaccharides is enhanced. With respect to adaptive immunity, PFOS reduces the total numbers of thymocytes and splenocytes and subpopulations thereof in a dose dependent fashion. Furthermore, comparison of wild-type mice and the corresponding knock-out strain lacking peroxisome proliferator-activated receptor-alpha revealed that these immunological changes are partially dependent on this receptor. Our further studies also show that sub-chronic dietary exposure to an environmentally relevant dose of PFOS does not alter the cellularity of the thymus and spleen and exerts no influence on humoral immune responses.

To facilitate examination of the effects of PFOA and PFOS on the hepatic immune system, we developed a procedure for mechanical disruption that yields a larger number of functionally competent immune cells from this organ. In our last study, lower doses of PFOA or PFOS induced hypertrophy of hepatocytes and altered the hepatic immune status. Thus, we find that short-term, high- and low-dose exposure of mice to these fluorochemicals is immunohepatotoxic.

Abstract [sv]

Perfluorooktanat (PFOA) och perfluorooktansulfonat (PFOS) som tillverkas för många olika industri och konsumentprodukter, är globalt förekommande miljögifter. Deras ackumulering i människor och djur ger upphov till en stark oro för hälsoproblem.

Vi har granskat effekterna av PFOA och PFOS på det medfödda, ospecifika immunförsvaret. Exponering för höga doser via maten under kort tid minskar det totala antalet cirkulerande vita blodkroppar samt delpopulationerna.. Immunsvaret ökar dock efter stimulering med bakteriella lipopolysaccharider både in vitro och in vivo , dvs produktionen av proinflammatoriska cytokiner av makrofager i bukhålan och benmärgen, men inte i mjälten ökar.. När det gäller adaptiv, specifik immunitet minskar PFOS det totala antalet tymocyter och splenocyter och deras olika subpopulationer. Vid exponering för lägre doser av PFOS induceras hepatomegali utan att påverka tymus eller mjälten.   Vi kunde visa att peroxisomal proliferator-aktiverad receptor-alfa medierar effekterna utav PFOS i tymus samt delar av effekterna av PFOS i mjälten genom att använda möss som saknade denna receptor. . Dettastöds av vår studie med subkronisk exponering för en miljömässig dos av PFOS vilken inte ändrade den cellulära sammansättningen i vare sig  tymus eller mjälte och inte hade  något inflytande på det humorala immunsvaret.

För att underlätta studier av hur PFOA och PFOS påverkar immunsystemet i levern utvecklade vi en metod för framrening av immunceller via mekanisk sönderdelning av levern, vilket gavett större antal av funktionella  immunceller från detta organ. I vår sista studie kunde vi påvisa att lägre doser av PFOA eller PFOS inducerade hypertrofi av hepatocyter samt en påverkan av leverns immunförsvar.

Place, publisher, year, edition, pages
Stockholm: Department of Biochemistry and Biophysics, Stockholm University, 2011. 126 p.
Perfluorooctanoate, Perfluorooctane sulfonate, Peroxisome proliferator-activated receptor-alpha, Hepatomegaly, Immunotoxicity, Thymus, Spleen
National Category
Natural Sciences
Research subject
urn:nbn:se:su:diva-63180 (URN)978-91-7447-381-0 (ISBN)
Public defence
2011-11-21, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 16 B, Stockholm, 10:00 (English)
Available from: 2011-10-30 Created: 2011-10-11 Last updated: 2011-11-15Bibliographically approved

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