Induction of Fas ligand (CD95L) by the toxic mistletoe lectins in human lymphocytes.
BACKGROUND
Fas ligand (FasL, CD95L) predominantly expressed on activated cytotoxic T cells and NK cells triggers apoptosis in Fas receptor (Apo-1, CD95) positive target cells. We investigated the expression of FasL, Fas and tumor necrosis factor (TNF) receptor 1 (TNF-R1, CD120a) on cultured human lymphocytes and leukemic T and B cells.


METHODS
Lymphocytes from six healthy individuals, from four patients with chronic lymphocytic T or B cell leukaemia, and leukemic Molt-4 cells were incubated with the apoptosis- inducing mistletoe lectins (ML I and ML III).


RESULTS
Incubation of differentiated lymphocytes with the ML resulted in a significant upregulation of FasL in the surviving CD4+ T helper cells, CD8+ cells and CD19+ B cells. Similarly, the TNF receptor expression increased, while the Fas molecule decreased. In contrast, FasL was not induced in leukemic cells.


CONCLUSIONS
Apart from a direct induction of apoptosis in response to an inhibition of protein synthesis by the enzymic ML A chain, ML treatment may indirectly induce apoptosis in Fas+ tumour cells through activated FasL+ lymphocytes.
Büssing
A
A
Department of Applied Immunology, University Witten/Herdecke, Communal Hospital, Germany. ArBuess@t-online.de
Stein
G M
GM
Pfüller
U
U
Schietzel
M
M
D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics; D018941:Antigens, CD19 / Q000032:analysis; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D053222:Fas Ligand Protein; D005786:Gene Expression Regulation / Q000187:drug effects*; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D006801:Humans; D015448:Leukemia, B-Cell / Q000473:pathology; D015458:Leukemia, T-Cell / Q000473:pathology; D016131:Lymphocyte Subsets / Q000187:drug effects* / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism; D028321:Plant Preparations; D010940:Plant Proteins; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis / Q000235:genetics; D047888:Receptors, Tumor Necrosis Factor, Type I; D054788:Ribosome Inactivating Proteins; D054790:Ribosome Inactivating Proteins, Type 2; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D014118:Toxins, Biological / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000096:biosynthesis / Q000235:genetics
D015703:Antigens, CD; D018941:Antigens, CD19; D000972:Antineoplastic Agents, Phytogenic; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D028321:Plant Preparations; D010940:Plant Proteins; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D054790:Ribosome Inactivating Proteins, Type 2; D014118:Toxins, Biological; D019014:fas Receptor; C488862:mistletoe lectin I; C488864:mistletoe lectin III; C009674:ribosome inactivating protein, Viscum; D054788:Ribosome Inactivating Proteins