Toxic proteins from European mistletoe (Viscum album L.): increase of intracellular IL-4 but decrease of IFN-gamma in apoptotic cells.
BACKGROUND
Mistletoe lectins (ML), the major biologically active components of mistletoe extracts, which are used for adjuvant cancer therapy, induce apoptosis in lymphocytes and tumor cells. In addition, ML at toxic concentrations induce the release of cytokines, but it remains unclear as to whether dying or activated cells are responsible.


METHODS
By flow cytometry, expression of IFN-gamma, IL-4, apoptosis marker Apo2.7 and anti-apoptotic Bcl-2 proteins were analyzed in response to ML or viscotoxins (VT) in PBMC from controls and plasmocytoma cells (U-266).


RESULTS
While ML inhibited PMA/Ca-ionophore/monensin co-stimulated IFN-gamma production, they increased IL-4 expression in CD8+ and CD4+ T-cells. Thereby, IL-4 was mainly expressed in apoptotic cells with a low level of Bcl-2 proteins. In contrast, the cell membrane permeabilising VT induced complete loss of Bcl-2 proteins but did not stimulate IL-4 production within 24 hours, indicating that IL-4 expression is related to apoptosis but not to necrosis.


CONCLUSIONS
Despite the role of IL-4 during activation of type2 T-helper cells, IL-4 expression may play an important yet undefined role during apoptosis of normal and tumor cells.
Krebsforschung Herdecke, Department of Applied Immunology, University Witten/Herdecke, Communal Hospital, Germany. stein.g@debitel.net
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Stein
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Pfüller
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Schietzel
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Büssing
D017209:Apoptosis; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D015847:Interleukin-4 / Q000378:metabolism*; D014784:Mistletoe / Q000737:chemistry / Q000633:toxicity*; D028321:Plant Preparations; D010940:Plant Proteins; D010946:Plants, Medicinal; D010954:Plasmacytoma / Q000378:metabolism / Q000473:pathology; D054790:Ribosome Inactivating Proteins, Type 2; D014118:Toxins, Biological / Q000633:toxicity*; D014407:Tumor Cells, Cultured
D028321:Plant Preparations; D010940:Plant Proteins; D054790:Ribosome Inactivating Proteins, Type 2; D014118:Toxins, Biological; C009674:ribosome inactivating protein, Viscum; D015847:Interleukin-4; D007371:Interferon-gamma; C488038:viscotoxin