Modulation of human blood lymphocyte cytotoxicity by the phorbol ester tumor promoter P(Bu)2: increase of target binding, impairment of effector recycling, and activation of lytic potential which is independent of IL-2.
Treatment of lymphocytes with the tumor promotor P(Bu)2 enhanced their target-binding capacity. In the conventional 51Cr-release assay, the cytotoxic potential of lymphocytes pretreated with P(Bu)2 for a short time was reduced while after prolonged treatment their function was increased. The peak of lytic potential was attained after 15 hr of exposure. Comparison of the cytotoxic results obtained in suspension and immobilized conjugate assays suggested that P(Bu)2 treatment causes an impairment of the recycling capacity of lymphocytes. After prolonged exposure, the lytic machinery became activated as reflected by the reduced time elapsing after contact between effectors and targets and the delivery of lethal hit. The activation was also observed in the immobilized agarose assay. It was reflected by the elevated proportion of damaged targets that were bound to the treated lymphocytes. The P(Bu)2- and interferon-induced augmentation of lytic potential is achieved through different mechanisms. Combination treatment applied to the effectors in sequence (first P(Bu)2 followed by interferon), resulted in an additive effect. Similarly, simultaneous treatment with IL-2 and P(Bu)2 also gave an additive increase in cytotoxicity. Addition of antibodies directed against IL-2 did not abrogate the P(Bu)2 effect. Consequently, neither interferon nor IL-2 are involved in the phorbol ester-induced cytotoxic function.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000502:physiology; D002051:Burkitt Lymphoma / Q000276:immunology; D002452:Cell Count; D002460:Cell Line; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology; D007376:Interleukin-2 / Q000276:immunology / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000276:immunology; D007700:Kinetics; D007951:Leukemia, Myeloid / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D015240:Phorbol 12,13-Dibutyrate; D010703:Phorbol Esters / Q000494:pharmacology*; D010704:Phorbols / Q000494:pharmacology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000911:Antibodies, Monoclonal; D007370:Interferon Type I; D007376:Interleukin-2; D010703:Phorbol Esters; D010704:Phorbols; D015240:Phorbol 12,13-Dibutyrate