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Cadmium-induced apoptosis and phenotypic changes in mouse thymocytes
1Department of Environmental Health, Sun Yat-sen University of Medical Sciences, Guangzhou, PR of China.
Abstract:
At present cadmium (Cd)-induced immunotoxicity and the mechanisms involved have not been fully elucidated. The main objective of the present study is to explore the apoptogenic property of Cd in primary cultured mouse thymocytes and its effect on cell surface marker expression and phenotypic changes. Cd-induced thymocyte apoptosis was determined by TdT-mediated dUTP nick end labeling (TUNEL) assay, DNA content/cell cycle analysis and DNA gel electrophoresis. The results showed that Cd was able to cause apoptosis in mouse thymocytes in a time- and dose-dependent manner. Moreover, different subsets of thymocytes possessed different susceptibility to the apoptotic effect of Cd, in the order of CD8+ > CD4- CD8- (double negative cells, DN) > CD4+ CD8+ (double positive cells, DP) > CD4+. Cd treatment also altered thymocyte surface marker expression, leading to evident phenotypic changes. Such changes were characterized by a decline in DP cells and a marked decrease in CD4+/CD8+ ratio, mainly due to a significant increase in CD8+ subsets. These observations help to obtain a better understanding of the immunotoxic and immunomodulatory effects of Cd.
Insights
Cadmium exposure induces programmed cell death (apoptosis) in mouse thymocytes in a dose-dependent manner. This heavy metal alters immune cell populations, impacting T-cell development and function.
Area of Science:
- Immunology
- Toxicology
- Cell Biology
Background:
- Cadmium (Cd) is a toxic heavy metal with known immunotoxic effects.
- The precise mechanisms of Cd-induced immunotoxicity, particularly thymocyte apoptosis, remain unclear.
Purpose of the Study:
- To investigate the apoptogenic effects of cadmium on primary mouse thymocytes.
- To analyze cadmium's impact on thymocyte surface marker expression and phenotypic alterations.
Main Methods:
- Primary mouse thymocytes were cultured and exposed to varying concentrations and durations of cadmium.
- Apoptosis was assessed using TdT-mediated dUTP nick end labeling (TUNEL) assay, DNA content/cell cycle analysis, and DNA gel electrophoresis.
- Flow cytometry was employed to evaluate changes in thymocyte surface marker expression and cell phenotypes.
Main Results:
- Cadmium exposure induced thymocyte apoptosis in a time- and dose-dependent manner.
- Susceptibility to cadmium-induced apoptosis varied among thymocyte subsets: CD8+ > double-negative (DN) > double-positive (DP) > CD4+.
- Cadmium treatment led to a decrease in DP cells, a reduced CD4+/CD8+ ratio, and an increase in CD8+ subsets, indicating significant phenotypic changes.
Conclusions:
- Cadmium triggers apoptosis in mouse thymocytes through specific mechanisms.
- Cadmium exposure significantly alters thymocyte populations and surface marker expression, contributing to its immunotoxic effects.
- These findings enhance the understanding of cadmium's immunomodulatory impact on the immune system.