Skip to main content
SpringerLink
Log in

Improvement of human dendritic cell culture for immunotoxicological investigations

  • Published:
Cell Biology and Toxicology Aims and scope Submit manuscript

Abstract

A toxic injury such as a decrease in the number of immature dendritic cells caused by a cytotoxic effect or a disturbance in their maturation process can be responsible for immunodepression. There is a need to improve in vitro assays on human dendritic cells used to detect and evaluate adverse effects of xenobiotics. Two aspects were explored in this work: cytotoxic effects of xenobiotics on immature dendritic cells, and the interference of xenobiotics with dendritic cell maturation. Dendritic cells of two different origins were tested. Dendritic cells obtained either from umbilical cord blood CD34+ cells or, for the first time, from umbilical cord blood monocytes. The cytotoxicity assay on immature dendritic cells has been improved. For the study of the potential adverse effects of xenobiotics on the maturation process of dendritic cells, several parameters were selected such as expression of markers (CD86, CD83, HLA-DR), secretion of interleukins 10 and 12, and proliferation of autologous lymphocytes. The relevance and the efficiency of the protocol applied were tested using two mycotoxins, T-2 toxin and deoxynivalence, DON, which are known to be immunosuppressive, and one phycotoxin, domoic acid, which is known not to have any immunotoxic effect. Assays using umbilical cord monocyte dendritic cell cultures with the protocol defined in this work, which involves a cytotoxicity study followed by evaluation of several markers of adverse effects on the dendritic cell maturation process, revealed their usefulness for investigating xenobiotic immunotoxicity toward immune primary reactions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

DC:

dendritic cell

DON:

deoxynivalenol

FBS:

fetal bovine serum

FITC:

isothiocya-nate

GM-CSF:

granulocyte-macrophage colony-stimulating factor

M-DC:

monocyte-derived dendritic cells

PBS:

phosphate-buffered saline

PE:

phycoerythrin

References

  • Caux C, Saeland S, Favre C, Duvert V, Mannomi P, Banchereau J. TNF-uα strongly potentiates interleukin-3 and GM-CSF induced proliferation of human CD34 hematopoietic progenitor cell. Blood. 1990;75:2292–8.

    PubMed  CAS  Google Scholar 

  • Caux C, Dezutter-Dambuyant C, Schmitt D, Banchereau J. GM-CSF and TNF-uα cooperate in the generation of dendritic Langerhans cells. Nature. 1992;360:258–61.

    Article  PubMed  CAS  Google Scholar 

  • Clark GJ, Angel N, Kato M, et al. The role of dendritic cells in the innate immune system. Microbes Infect. 2000;2:257–72.

    Article  PubMed  CAS  Google Scholar 

  • Coutant KD, De Brugerolle De Fraissinette A, Cordier A, Ulrich P. Modulation of the activity of human monocyte-derived dendritic cells by chemical haptens, a metal allergen and a staphylococcal superantigene. Toxicol Sci. 1998;52:189–98.

    Article  Google Scholar 

  • Froquet R, Sibiril Y, Parent-Massin D. Improvement of megakaryocytic progenitor culture for toxicological investigations.Toxicol In Vitro. 2001;15:691–9.

    Article  PubMed  CAS  Google Scholar 

  • Froquet R, Arnold F, Batina P, Parent-Massin D. Do trichothecenes reduce viability of circulating blood cells and modify haemostasis parameters? Mycopathologia. 2003;156:349–56.

    Article  PubMed  CAS  Google Scholar 

  • Laupeze B, Amiot L, Sparfel L, Le Ferrec E, Fauchet R, Fardel O. Polycyclic aromatic hydrocarbons affect functional differentiation and maturation of human monocyte-derived dendritic cells. J Immunol. 2002;168:2652–8.

    PubMed  CAS  Google Scholar 

  • Lautraite S, Parent-Massin D, Rio B, Hoellinger H. Comparison of toxicity induced by T-2 toxin on human and rat granulo-monocytic progenitors with an in vitro model. Hum Exp Toxicol. 1995;14: 672–8.

    PubMed  CAS  Google Scholar 

  • Lautraite S, Parent-Massin D, Rio B, Hoellinger H. In vitro toxicity induced by deoxynivalenol (DON) on human and rat granulo-monocytic progenitors. Cell Biol Toxicol. 1997;13: 175–83.

    Article  PubMed  CAS  Google Scholar 

  • Parent-Massin D. Haematotoxicity of trichothecenes. Toxicol Lett. 2004;153:75–81.

    Article  PubMed  CAS  Google Scholar 

  • Pestka J, Zhou HR, Moon Y, Chung YJ. Cellular and molecular mechanisms for immune modulation by deoxynivalenol and other trichothecenes: unraveling a paradox. Toxicol lett. 2004;153:61–73.

    Article  PubMed  CAS  Google Scholar 

  • Rio B, Lautraite S, Parent-Massin D. In vitro toxicity of trichothecenes on human erythroblastic progenitors. Hum Exp Toxicol. 1997;16:673–9.

    Article  PubMed  CAS  Google Scholar 

  • Rio B, Froquet R, Sibiril Y, Parent-Massin D. Relevance of erythroblast progenitor clonogenic assays in toxicological studies. ATLA. 1999;27:363. [Abstract].

    Google Scholar 

  • Romani N, Gruner S, Brang D, et al. Proliferating dendritic cell progenitors in human blood. J Exp Med. 1994;180:83–93.

    Article  PubMed  CAS  Google Scholar 

  • Romani N, Reider D, Heuer M, et al. Generation of mature dendritic cells from human blood. An improved method with special regard to clinical applicability. J Immunol Methods. 1996;196:137–51.

    CAS  Google Scholar 

  • Sallusto F, Lanzavecchia A. Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor alpha. J Exp Med. 1994;179:1109–18.

    Article  PubMed  CAS  Google Scholar 

  • Steinman RM. The dendritic cell system and its role in immunogenecity. Annu Rev Immunol. 1991;9: 271–96.

    Article  PubMed  CAS  Google Scholar 

  • Verhasselt V, Buelens C, Willems F, De Groote D, Haeffner-Cavaillon N, Goldman M. Bacterial lipopolysaccharide stimulates the production of cytokines and the expression of costimulatory molecules by human peripheral blood dendritic cells: evidence for a CD14-dependent pathway. J Immunol. 1997;158:2919–25.

    PubMed  CAS  Google Scholar 

  • Whittle K, Gallacher S. Marine toxins. Br Med Bul. 2000;56:236–53.

    Article  CAS  Google Scholar 

  • Zhou LJ, Tedder, T.F. Human blood dendritic cells selectively express CD83, a member of the immunoglobulin superfamily. J Immunol. 1995;154:3821–35.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratoire de Toxicologie Alimentaire, Technopôle Brest-Iroise, Université de Bretagne Occidentale, Plouzané, France

    N. Hymery, Y. Sibiril & D. Parent-Massin

Authors
  1. N. Hymery
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Y. Sibiril
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. D. Parent-Massin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to D. Parent-Massin.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hymery, N., Sibiril, Y. & Parent-Massin, D. Improvement of human dendritic cell culture for immunotoxicological investigations. Cell Biol Toxicol 22, 243–255 (2006). https://doi.org/10.1007/s10565-006-0180-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10565-006-0180-3

Keywords

Search

Navigation