Immunotoxicological Study of Depleted Uranium

The purpose of this study was to examine toxicity of depleted uranium (DU) to the immune system and the gene expression profile of DU-exposed immune cells including peritoneal macrophages, primary CD4⁺ T-cells and T Cell Hybridoma (TCH) PLP1 5B6. Flow cytometry analysis of annexin-V and Propidium Iodide (PI) binding revealed that DU causes death in those cells at various concentrations. The non-cytotoxic concentrations of DU determined in macrophages, primary CD4⁺ T-cells, and T cells hybridoma are 50µM, 100 µM, and 500 µM, respectively. Findings also revealed that DU-exposed macrophages are able to promote CD4⁺ T-cell proliferation in a concentration dependent manner.

In addition, mouse cytokine cDNA array and a confirmative method (Quantitative RT-PCR or Northern blot) were used to study the gene expression profile of DU-exposed cells. The results demonstrate that DU can modulate macrophage gene expressions such as NF-kBp65, Midkine, c-jun, and IL-10 that are related to multiple signal transduction pathways, suggesting possible involvement of DU in immune or inflammatory response, cancer development, and chronic disease. Array analysis of DU-exposed primary CD4⁺ T-cells reveals that DU up-regulates gene expression of a number of cytokines such as IL-5, Midkine, indicating the activities of DU in inducing cancer development, promoting eosinophil-related inflammatory diseases, and encouraging Th2 polarization. Furthermore, the possible involvement of DU in cancer development was demonstrated in TCH using microarray analysis. However, no Th2 cytokine was up-regulated in TCH after DU exposure.