Suppression of the in vitro specific antibody response by 12-O-tetradecanoylphorbol-13-acetate (TPA) in the mouse.
The tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA), has several effects on the immune system. The effect of TPA on the in vitro antibody response to sheep red blood cells (sRBC) was studied. Spleen cells treated in vitro with TPA resulted in a dose-dependent inhibition of the IgM antibody forming cell (AFC) response with an IC50 of 0.74 nM. Nontumor promoting analogs at concentrations up to 1000 nM had no effect on this system. 2-Mercaptoethanol (2ME), which is known to augment macrophage function in this assay, did not reverse the inhibition. Spleen cells were separated into plastic adherent cells (ADC) and nonadherent cells (NAC). When NAC were treated with TPA and cultured with untreated ADC, the inhibition was seen. However, treating the ADC alone did not result in an inhibition. These results show that TPA will suppress the in vitro antibody response in the mouse and that the suppression is due to a selective effect on the plastic nonadherent cell population. The study of these effects of TPA may allow us to gain insight into the mechanism of its tumor promoting activity and to use it as a tool to study the modulation of the immune system.
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects*; D002448:Cell Adhesion / Q000187:drug effects; D004912:Erythrocytes / Q000276:immunology; D005260:Female; D007165:Immunosuppression Therapy; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010703:Phorbol Esters / Q000494:pharmacology*; D010704:Phorbols / Q000494:pharmacology*; D012756:Sheep; D013154:Spleen / Q000276:immunology; D013329:Structure-Activity Relationship; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D010703:Phorbol Esters; D010704:Phorbols; D013755:Tetradecanoylphorbol Acetate