Sodium arsenite reduces proliferation of human activated T-cells by inhibition of the secretion of interleukin-2.
Arsenic (As) is a common metalloid which contaminates drinking water in several regions of the world and chronic exposure is associated with skin, lung, bladder, and kidney cancer. Previous studies suggest that arsenic exposure leads to a diminution of phytohemaglutinin (PHA) stimulated T cell proliferation in humans. In order to understand the mechanism of this suppression, the effect of As was evaluated on the expression of CD25, and IL-2 secretion in human peripheral blood mononuclear cells (PBMC). Inhibition of proliferation was observed in all donors studied. Most of the donors did not show any change in the expression of CD25, but IL-2 secretion was inhibited in 6 of the 7 donors tested. Proliferative inhibition was due to a suboptimal levels of IL-2 secreted by lymphocytes, since the addition of recombinant IL-2 to the cultures reversed in a dose-dependent fashion the inhibitory effect of As. The determination of the mRNA of IL-2 and the intracellular IL-2 levels demonstrated that the inhibition is not at the transcriptional level. Electron microscopy studies revealed that cellular ultrastructure in Golgi apparatus, mitochondria, cytoskeleton, and perinuclear membrane were altered. These alterations suggest that due to sodium arsenite effects on cytoskeleton, the intracellular secretion of proteins is affected, including the one of IL-2, leading to an impaired proliferation of the T cells when stimulated with PHA.
D000328:Adult; D018053:Arsenites / Q000633:toxicity*; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000187:drug effects; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D008854:Microscopy, Electron; D015375:Receptors, Interleukin-2 / Q000032:analysis; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000648:ultrastructure