Comparison between the mechanisms of action of plant toxins ricin and viscumin on the stage of intracellular dissociation.
Pharmacological effects of mistletoe extracts are determined by the concentration of three toxic lectins: mistletoe lectin I (MLI, or viscumin), MLII, MLIII. These proteins, as well as ricin, belong to ribosome-inactivating proteins type 2 (RIP2). However, the extracts from the plant Ricinus communis, containing ricin, are highly toxic. Ricin is about 30 times more effective in cell culture than viscumin. The dissociation of subunits and the transmembrane transport of catalytic subunit into the cytoplasm are needed to obtain the cytotoxic effect of RIP2. In this paper, hybridomas producing monoclonal antibodies against catalytic subunits of ricin and viscumin are described. Monoclonal antibodies against different epitopes, including one localized in intra-subunit area of catalytic subunits of ricin and viscumin, do not inhibit the enzymatic activity of these proteins in cell-free system. These hybridomas are resistant to the cytotoxic action of native toxins. Protective effect of antibodies are about the same for both toxins, though the dissociation of the subunits of ricin is more effective. The causes of the differences in activity of plant toxins as pharmacological agents, and the importance of above mentioned epitopes for neutralizing antibodies at the clinical applications of mistletoe extracts are discussed.
ProBioGen AG, Berlin, Germany. tonevits@genetika.ru
Alexander
A
Tonevitsky
Igor
I
Agapov
Olga
O
Chelnokova
Mikhail
M
Moisenovich
Uwe
U
Marx
D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000737:chemistry; D000921:Antibody-Producing Cells / Q000187:drug effects; D000972:Antineoplastic Agents, Phytogenic / Q000276:immunology / Q000633:toxicity*; D001710:Biotin / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects; D004229:Dithiothreitol / Q000494:pharmacology; D000939:Epitopes / Q000187:drug effects; D006825:Hybridomas / Q000187:drug effects; D007124:Immunoenzyme Techniques; D051379:Mice; D028321:Plant Preparations; D010940:Plant Proteins; D054790:Ribosome Inactivating Proteins, Type 2; D012276:Ricin / Q000276:immunology / Q000633:toxicity*; D013778:Tetrazolium Salts; D013844:Thiazoles; D014118:Toxins, Biological / Q000276:immunology / Q000633:toxicity*
D000911:Antibodies, Monoclonal; D000972:Antineoplastic Agents, Phytogenic; D000939:Epitopes; D028321:Plant Preparations; D010940:Plant Proteins; D054790:Ribosome Inactivating Proteins, Type 2; D013778:Tetrazolium Salts; D013844:Thiazoles; D014118:Toxins, Biological; C009674:ribosome inactivating protein, Viscum; D001710:Biotin; D012276:Ricin; C022616:thiazolyl blue; D004229:Dithiothreitol