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Lead and cadmium at very low doses affect in vitro immune response of human lymphocytes
1Istituto di Igiene, Università degli Studi, Modena, Italy.
Insights
Lead exposure enhanced immunoglobulin production in human lymphocytes, while cadmium showed variable effects. Metal accumulation within cells influenced these immune responses, suggesting potential genetic factors in cadmium
Area of Science:
- Immunotoxicology
- Environmental Health
- Cellular Immunology
Background:
- Heavy metals like lead (Pb) and cadmium (Cd) are environmental contaminants with known toxic effects.
- Understanding their impact on the human immune system, particularly immunoglobulin (Ig) production, is crucial for public health.
- Lymphocytes play a central role in adaptive immunity, and their function can be modulated by external factors.
Purpose of the Study:
- To investigate the in vitro effects of lead chloride and cadmium chloride on immunoglobulin production by human lymphocytes.
- To determine the dose-dependency and cellular uptake of lead and cadmium in relation to immune response.
- To explore the variability in immune response to cadmium and potential underlying genetic factors.
Main Methods:
- Human lymphocytes were cultured for 7 days with varying concentrations of lead chloride and cadmium chloride.
- Immunoglobulin production was assessed, with and without pokeweed mitogen (PWM) activation.
- Cellular accumulation and distribution of lead and cadmium were measured using analytical techniques.
Main Results:
- Lead exposure, within the range of human exposure, significantly enhanced Ig production in both activated and unstimulated lymphocytes, in a dose-dependent manner.
- Cadmium exhibited dose-independent mitogenic activity in unstimulated cells but did not significantly affect Ig secretion in PWM-activated cells.
- Significant intraindividual variability in immune response to cadmium was observed, with differential metal accumulation in cellular fractions based on lymphocyte activation state.
Conclusions:
- Lead uptake and intracellular distribution appear to influence its stimulatory effect on Ig production.
- The variable immune response to cadmium suggests a role for genetic factors, potentially related to metallothionein (MT) inducibility.
- These findings highlight the differential immunotoxicological profiles of lead and cadmium and underscore the complexity of metal-environment-immune interactions.
Abstract:
The effect of lead chloride and cadmium chloride on in vitro immunoglobulin (Ig) production by human lymphocytes was investigated. After 7 days in culture, lead added in the range of human exposure (207-1035 micrograms/liter) significantly enhanced Ig production either when cells were activated by pokeweed mitogen (PWM) or not. The effect was dose-dependent and was related to the Pb we measured in the extracellular medium and in the cells. Independently of the mitogen addition, about 2% of the Pb added was accumulated in the cells, most being associated with the nuclear fraction. Those findings suggest that the Pb effects could depend on its uptake and distribution in the cells. Cadmium added in the 50-500 nM range exhibited a dose-independent mitogenic activity in unstimulated cells, whereas the Ig secretion was not significantly affected by Cd when cells were PWM-activated. A considerable intraindividual variability, however, was observed when blood donors were separately examined, with both an increase, a decrease, or no variation on Ig production. Furthermore, higher percentages of Cd were accumulated in the nuclear fraction, and lower in the cytosol and precipitate, in PWM-activated compared to resting lymphocytes. Genetic factors could be of importance for the observed variability of the immune response to cadmium, and we support the hypothesis that differences in the metallothionein (MT) inducibility could play a role.