Triethyllead-induced inhibition of proliferation of normal human lymphocytes through decreased expression of the Tac chain of interleukin 2 receptor.
Triethyllead (Et3Pb+) in concentrations 10(-5) to 10(-6) M has been shown to inhibit several key cellular molecular systems. In order to evaluate the effect of Et3Pb+ on the human immune system, the mitogen-induced cell proliferation of peripheral blood mononuclear cells was studied in the presence of Et3Pb+. Preincubation of normal T-lymphocytes with 10(-6) M Et3Pb+ for 1-4 h, which has been shown to be non-cytotoxic, was sufficient to inhibit subsequent mitogenic-induced cell growth. The Et3Pb(+)-induced impairement of the in vitro proliferation of mitogen-activated normal T-cells was due to a dose-dependent decreased expression of the p55 polypeptide chain (Tac molecule) of the interleukin-2 receptor (IL-2-R), which could not be enhanced by exogeneously added recombinant interleukin 2 (rIL-2). Conversely, the same concentrations of Et3Pb+ could not inhibit the mitogen-induced expression of MHC class II molecules and the transferin receptor on activated T-cells. The impaired membrane expression of p55 on T-cells induced by Et3Pb+ was due to a decrease of Tac mRNA transcripts as showed by Northern blot analysis. This effect seems to be specific since in parallel experiments Et3Pb+ could not inhibit both the accumulation of actin mRNA and the production of IL-2 by Et3Pb(+)-treated mitogen-activated cells. The effect of this organolead compound was also associated with a dose-dependent decrease of the Na(+)-K(+)-ATPase activity of normal lymphocytes. These results indicate that Et3Pb+ could affect specifically T-cell proliferative responses through an imbalance of the IL-2/IL-2-R system.
Stournaras
C
C
Department of Basic Sciences, School of Medicine, University of Crete, Iraklion, Greece.
Spanakis
E
E
Perraki
M
M
Athanasiou
M
M
Thanos
D
D
Georgoulias
V
V
D015152:Blotting, Northern; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007376:Interleukin-2 / Q000032:analysis / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000502:physiology; D009942:Organometallic Compounds / Q000633:toxicity*; D010641:Phenotype; D012333:RNA, Messenger / Q000302:isolation & purification; D015375:Receptors, Interleukin-2 / Q000187:drug effects* / Q000235:genetics; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D014158:Transcription, Genetic
D007376:Interleukin-2; D009942:Organometallic Compounds; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; C010360:triethyllead