Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Dietary exposure to perfluorooctanoate or perfluorooctane sulfonate induces hypertrophy in centrilobular hepatocytes and alters the hepatic immune status in mice
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.
Show others and affiliations
2010 (English)In: International Immunopharmacology, ISSN 1567-5769, E-ISSN 1878-1705, Vol. 10, no 11, 1420-7 p.Article in journal (Refereed) Published
Abstract [en]

It is well established that exposure of mice to perfluorooctanoate (PFOA) or perfluorooctane sulfonate (PFOS) induces hepatomegaly and, concurrently, immunotoxicity. However, the effects of these perfluorochemicals on the histology and immune status of the liver have not been yet investigated and we have examined these issues here. Dietary treatment of male C57BL/6 mice with 0.002% (w/w) PFOA or 0.005% (w/w) PFOS for 10 days resulted in significant reductions in serum levels of cholesterol and triglycerides, a moderate increase in the serum activity of alkaline phosphatase (ALP) and hepatomegaly, without affecting other immune organs. This hepatomegaly was associated with marked hypertrophy of the centrilobular hepatocytes, with elevated numbers of cytoplasmic acidophilic granules and occasional mitosis. Furthermore, dietary exposure to PFOA or PFOS altered the hepatic immune status: whereas exposure to PFOA enhanced the numbers of total, as well as of phenotypically distinct subpopulations of intrahepatic immune cells (IHIC), and in particular the presumptive erythrocyte progenitor cells, treatment with PFOS enhanced only the numbers of hepatic cells that appear immunophenotypically to be erythrocyte progenitors, without affecting other types of IHIC. In addition, exposure to these compounds attenuated hepatic levels of tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ) and interleukin-4 (IL-4). Furthermore, the exposed animals exhibited a significant increase in hepatic levels of erythropoietin, a hormone required for erythropoiesis. Thus, in mice, PFOA- and PFOS-induced hepatomegaly is associated with significant alterations in hepatic histophysiology and immune status, as well as induction of hepatic erythropoiesis.

Place, publisher, year, edition, pages
2010. Vol. 10, no 11, 1420-7 p.
Keyword [en]
Perfluorooctane sulfonate, Perfluorooctanoate, Hepatomegaly, Hepatic immune system, Intrahepatic immune cells, Erythropoiesis, Erythropoietin
National Category
Natural Sciences
Research subject
Biophysics; Biochemistry
Identifiers
URN: urn:nbn:se:su:diva-51627DOI: 10.1016/j.intimp.2010.08.009PubMedID: 20816993OAI: oai:DiVA.org:su-51627DiVA: diva2:385510
Available from: 2011-01-11 Created: 2011-01-11 Last updated: 2017-12-11Bibliographically 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.
Keyword
Perfluorooctanoate, Perfluorooctane sulfonate, Peroxisome proliferator-activated receptor-alpha, Hepatomegaly, Immunotoxicity, Thymus, Spleen
National Category
Natural Sciences
Research subject
Biochemistry
Identifiers
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)
Opponent
Supervisors
Available from: 2011-10-30 Created: 2011-10-11 Last updated: 2011-11-15Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Qazi, Mousumi RahmanNelson, B DeanDePierre, Joseph WAbedi-Valugerdi, Manuchehr
By organisation
Department of Biochemistry and Biophysics
In the same journal
International Immunopharmacology
Natural Sciences

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 81 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf