Skip to main content
SpringerLink
Log in

Mistletoe lectin transport by M-cells in follicle-associated epithelium (FAE) and IL-12 secretion in dendritic cells situated below FAE In Vitro

  • Research Articles
  • Drug Actions
  • Published:
Archives of Pharmacal Research Aims and scope Submit manuscript

Abstract

A galactose- and N-acetyl-D-galactosamine-specific lectin (Viscum album L. var. coloratum agglutinin, VCA), which is known for its anti-tumor activity, was isolated from Korean mistletoe. Mistletoe preparations have been given subcutaneously because of the unstability and poor absorption in the GI tract. In this study, we investigated the effect of incubation time and glucose on the VCA transport across the in vitro model of human FAE (follicle-associated epithelium) by two different cell models: Caco-2 cell monolayers mimicking human enterocytes and a model of the human FAE which is mainly composed of M-cells and enterocytes. As a result, the VCA transport across the FAE monolayer cells was higher and faster than the transport across the Caco-2 monolayer cells, and glucose increased VCA transport across both monolayer cells. In addition, IL-12 was secreted from myeloid DC1 and lymphoid DC2.4 cells which were co-treated simultaneously with LPS and VCA. Furthermore, the FAE model associated with underlying immune cells was established and VCA was added to the inserts apically. There was a greater IL-12 secretion in dendritic cells situated below FAE monolayer than Caco-2 monolayer. The results from this study provide important insight into the possible oral application of mistletoe on anti-tumor therapeutics.

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

References

  • Brayden, D. J. and Baird, A. W., Microparticle vaccine approaches to stimulate mucosal immunisation. Microbes Infect., 3, 867–876 (2001).

    Article  CAS  PubMed  Google Scholar 

  • Büssing, A., Biological and pharmacological properties of Viscum Album L., In Büssing, A. (Ed.). The Genus Viscum. Harwood Academic Publishers, Amsterdam, The Netherlands, pp. 123–182, (2000).

    Google Scholar 

  • Clark, M. A., Hirst, B. H., and Jepson, M. A., Lectin-mediated mucosal delivery of drugs and microparticles. Adv. Drug Deliv. Rev., 43, 207–223 (2000).

    Article  CAS  PubMed  Google Scholar 

  • Clark, M. A., Blair, H., Liang, L., Brey, R. N., Brayden, D., and Hirst, B. H., Targeting polymerised liposome vaccine carriers to intestinal M cells. Vaccine, 20, 208–217 (2001).

    Article  CAS  PubMed  Google Scholar 

  • Fernandez, N. C., Flament, C., Crépineau, F., Angevin, E., Vivier, E., and Zitvogel, L., Dendritic cells (DC) promote natural killer (NK) cell functions: dynamics of the human DC/NK cell cross talk. Eur. Cytokine Netw., 13, 17–27 (2002).

    CAS  PubMed  Google Scholar 

  • Frey, A. and Neutra, M. R., Targeting of mucosal vaccines to Peyer’s patch M cells. Behring Inst. Mitt., 98, 376–389 (1997).

    CAS  PubMed  Google Scholar 

  • Gebert, A., Rothkotter, H. J., and Pabst, R., M cells in Peyer’s patches of the intestine. Int. Rev. Cytol., 167, 91–159 (1996).

    Article  CAS  PubMed  Google Scholar 

  • Gebert, A. and Pabst, R., M cells at locations outside the gut. Semin. Immunol., 11, 165–170 (1999).

    Article  CAS  PubMed  Google Scholar 

  • Giannasca, P. J., Giannasca, K. T., Leichtner, A. M., and Neutra, M. R., Human intestinal M cells display the sialyl Lewis A antigen. Infect. Immun., 67, 946–953 (1999).

    CAS  PubMed  Google Scholar 

  • Gullberg, E., Leonard, M., Karlsson, J., Hopkins, A. M., Brayden, D., Baird, A. W., and Artursson, P., Expression of specific markers and particle transport in a new human intestinal M-cell model. Biochem. Biophys. Res. Commun., 279, 808–813 (2000).

    Article  CAS  PubMed  Google Scholar 

  • Hajto, T., Hostanska, K., Frei, K., Rordorf, C., and Gabius, H. J., Increased secretion of tumor necrosis factor α, interleukin 1, and interleukin 6 by human mononuclear cells exposed to β-galactoside-specific lectin from clinically applied mistletoe extract. Cancer Res., 50, 3322–3326 (1990).

    CAS  PubMed  Google Scholar 

  • Hajto, T., Hostanska, K., Fischer, J., and Saller, R., Immunomodulatory effects of Viscum album agglutinin-I on natural immunity. Anticancer Drugs, 8, 543–546 (1997).

    Article  Google Scholar 

  • Hata, M., Takahara, S., Tsuzaki, H., Ishii, Y., Nakata, K., Akagawa, K. S., and Satoh, K., Expression of Th2-skewed pathology mediators in monocyte-derived type 2 of dendritic cells (DC2). Immunol. Lett., 126, 29–36 (2009).

    Article  CAS  PubMed  Google Scholar 

  • Hostanska, K., Hajto, T., Spagnoli, G. C., Fischer, J., Lentzen, H., and Hermann, R., A plant lectin derived from Viscum album induces cytokine gene expression and protein production in cultures of human peripheral blood mononuclear cells. Nat. Immun., 14, 295–304 (1995).

    CAS  PubMed  Google Scholar 

  • Inaba, K., Metlay, J. P., Crowley, M. T., and Steinman, R. M., Dendritic cells pulsed with protein antigens in vitro can prime antigen-specific, MHC-restricted T cells in situ. J. Exp. Med., 172, 631–640 (1990).

    Article  CAS  PubMed  Google Scholar 

  • Jepson, M. A., Simmons, N. L., Savidge, T. C., James, P. S., and Hirst, B. H., Selective binding and transcytosis of latex microspheres by rabbit intestinal M cells. Cell Tissue Res., 271, 399–405 (1993).

    Article  CAS  PubMed  Google Scholar 

  • Kamei, N., Morishita, M., Ehara, J., and Takayama, K., Permeation characteristics of oligoarginine through intestinal epithelium and its usefulness for intestinal peptide drug delivery. J. Control. Release, 131, 94–99 (2008).

    Article  CAS  PubMed  Google Scholar 

  • Kerneis, S., Bogdanova, A., Kraehenbuhl, J. P., and Pringault, E., Conversion by Peyer’s patch lymphocytes of human enterocytes into M cells that transport bacteria. Science, 277, 949–952 (1997).

    Article  CAS  PubMed  Google Scholar 

  • Kovacs, E., Serum levels of IL-12 and the production of IFNgamma, IL-2 and IL-4 by peripheral blood mononuclear cells (PBMC) in cancer patients treated with Viscum album extract. Biomed. Pharmacother., 54, 305–310 (2000).

    Article  CAS  PubMed  Google Scholar 

  • Krawczyk, P., Wojas, K., Milanowski, P., and Roliński, J., Myeloid and lymphoid dendritic cells and cytotoxic T lymphocytes in peripheral blood of non-small cell lung cancer patient-a pilot study. Adv. Med. Sci., 51, 160–163 (2006).

    CAS  PubMed  Google Scholar 

  • Kucharzik, T., Lügering, N., Schmid, K. W., Schmidt, M. A., Stoll, R., and Domschke, W., Human intestinal M cells exhibit enterocyte-like intermediate filaments. Gut, 42, 54–62 (1998).

    Article  CAS  PubMed  Google Scholar 

  • Lelouard, H., Reggio, H., Roy, C., Sahuquet, A., Mangeat, P., and Montcourrier, P., Glycocalyx on rabbit intestinal M cells displays carbohydrate epitopes from Muc2. Infect. Immun., 69, 1061–1071 (2001).

    Article  CAS  PubMed  Google Scholar 

  • Liang, E., Kabcenell, A. K., Coleman, J. R., Robson, J., Ruffles, R., and Yazdanian, M., Permeability measurement of macromolecules and assessment of mucosal antigen sampling using in vitro converted M cells. J. Pharmacol. Toxicol. Methods, 46, 93–101 (2001).

    Article  CAS  PubMed  Google Scholar 

  • Lyu, S. Y., Park, S. M., Choung, B. Y., and Park, W. B., Comparative study of Korean (Viscum album var. coloratum) and European mistletoes (Viscum album). Arch. Pharm. Res., 23, 592–598 (2000).

    Article  CAS  PubMed  Google Scholar 

  • Lyu, S. Y. and Park, W. B., Transport of mistletoe lectin by M cells in human intestinal follicle-associated epithelium (FAE) in vitro. Arch. Pharm. Res., 31, 1613–1621 (2008).

    Article  CAS  PubMed  Google Scholar 

  • Lyu, S. Y. and Park, W. B., Mistletoe lectin modulates intestinal epithelial cell-derived cytokines and B cell IgA secretion. Arch. Pharm. Res., 32, 443–451 (2009).

    Article  CAS  PubMed  Google Scholar 

  • Markowska, M., Oberle, R., Juzwin, S., Hsu, C. P., Gryszkiewicz, M., and Streeter, A. J., Optimizing Caco-2 cell monolayers to increase throughput in drug intestinal absorption analysis. J. Pharmacol. Toxicol. Methods, 46, 51–55 (2001).

    Article  CAS  PubMed  Google Scholar 

  • Moyes, S. M., Smyth, S. H., Shipman, A., Long, S., Morris, J. F., and Carr, K. E., Parameters influencing intestinal epithelial permeability and microparticle uptake in vitro. Int. J. Pharm., 337, 133–141 (2007).

    Article  CAS  PubMed  Google Scholar 

  • Niedergang, F. and Kraehenbuhl, J., Much ado about M cells. Trends Cell Biol., 10, 137–141 (2000).

    Article  CAS  PubMed  Google Scholar 

  • Niedergang, F. and Kweon, M. N., New trends in antigen uptake in the gut mucosa. Trends Microbiol., 13, 485–490 (2005).

    Article  CAS  PubMed  Google Scholar 

  • Pielage, J. F., Cichon, C., Greune, L., Hirashima, M., Kucharzik, T., and Schmidt, M. A., Reversible differentiation of Caco-2 cells reveals galectin-9 as a surface marker molecule for human follicle-associated epithelia and M cell-like cells. Int. J. Biochem. Cell Biol., 39, 1886–1901 (2007).

    Article  CAS  PubMed  Google Scholar 

  • Pusztai, A., Grant, G., Gelencsér, E., Ewen, S. W. B., Pfüller, U., Eifler, R., and Bardocz, S., Effects of an orally administered mistletoe (type-2 RIP) lectin on growth, body composition, small intestinal structure, and insulin levels in young rats. J. Nutr. Biochem., 9, 31–36 (1998).

    Article  CAS  Google Scholar 

  • Rieux, A., Ragnarsson, E. G. E., Gullberg, E., Préat, V., Yves, J., Schneider, Y. J., and Artursson, P., Transport of nanoparticles across an in vitro model of the human intestinal follicle associated epithelium. Eur. J. Pharm. Sci., 25, 455–465 (2005).

    Article  PubMed  Google Scholar 

  • Rieux, A., Fievez, V., Théate, I., Mast, J., Préat, V., and Schneider, Y. J., An improved in vitro model of human intestinal follicle-associated epithelium to study nanoparticle transport by M cells. Eur. J. Pharm. Sci., 30, 380–391 (2007).

    Article  PubMed  Google Scholar 

  • Steinman, R. M. and Banchereau, J., Dendritic cells and the control of immunity. Nature, 392, 245–252 (1998).

    Article  PubMed  Google Scholar 

  • Tonevitsky, A. G., Agapov, I. I., Pevzner, I. B., Malyuchenko, N. V., Moisenovich, M. M., Pfueller, U., and Kirpichnikov, M. P., Cloning and expression of catalytic subunit of MLIII, the ribosome-inactivating protein from Viscum album. Biochemistry (Mosc)., 69, 642–650 (2004).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Herbal Medicinal Pharmacology, Daegu Haany University, Gyeongsan, 712-715, Korea

    Su-Yun Lyu

  2. College of Natural Sciences, Seoul Women’s University, Seoul, 139-774, Korea

    Won-Bong Park

Authors
  1. Su-Yun Lyu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Won-Bong Park
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Won-Bong Park.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lyu, SY., Park, WB. Mistletoe lectin transport by M-cells in follicle-associated epithelium (FAE) and IL-12 secretion in dendritic cells situated below FAE In Vitro . Arch. Pharm. Res. 33, 1433–1441 (2010). https://doi.org/10.1007/s12272-010-0918-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12272-010-0918-6

Key words

Search

Navigation