Modulation of receptors and cytotoxic response of tumor necrosis factor-alpha by various lectins.
The effects of various lectins on the interaction of the human cervical carcinoma cell line ME-180 with recombinant human tumor necrosis factor-alpha (rTNF-alpha) was investigated. rTNF-alpha is known to have cytotoxic effects on this tumor cell line and has been reported to interact with these cells through a single class of specific high affinity receptors (Kd = 0.45 nM; approximately 1790 binding sites/cell). Exposure of cells to concanavalin A (ConA) causes an approximately 2-fold increase in rTNF-alpha receptors without any significant change in their affinity constant (Kd = 0.36 nM; approximately 3662 binding sites/cell). This increase in receptor number is dependent on temperature, the time of exposure and dose of ConA, and does not require the synthesis of new proteins. In spite of an increased binding of rTNF-alpha to cells, the cell killing induced by rTNF-alpha is totally blocked by ConA. Cells are also protected by this lectin from the synergistic cytotoxic effects of rTNF-alpha and recombinant human interferon-gamma. Furthermore, it was also found that ConA decreases the rate of internalization and dramatically inhibits the release and degradation of rTNF-alpha by the cells. These results, overall, demonstrate that ConA increases total number of binding sites for rTNF-alpha but blocks the transduction of the signal for the cytotoxic response.
D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D003208:Concanavalin A / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D005260:Female; D006023:Glycoproteins / Q000378:metabolism* / Q000633:toxicity; D006801:Humans; D007700:Kinetics; D037102:Lectins / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins / Q000378:metabolism* / Q000633:toxicity; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000473:pathology
D006023:Glycoproteins; D037102:Lectins; D011956:Receptors, Cell Surface; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D003208:Concanavalin A; D003609:Dactinomycin