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Real-time Cytotoxicity Assays in Human Whole Blood
Published on: November 7, 2014
Effect of auranofin on antibody-dependent cellular cytotoxicity (ADCC) mediated by rat peripheral blood
Abstract:
Auranofin and other clinically used gold compounds were evaluated in vitro for effects on antibody-dependent cellular cytotoxicity (ADCC) of L929 fibroblast target cells mediated by adjuvant rat peripheral blood PMNs or mononuclear cells. Auranofin (10 microM) was found to be a potent inhibitor of PMNADCC. In contrast, gold sodium thiomalate (10-100 microM), gold thioglucose (10-1000 microM), and nongold substructures of auranofin (10 microM) were not inhibitory.. In continuous culture, gold sodium thiomalate and relatively low concentrations of auranofin (smaller than or equal to microM) significantly enhanced PMNADCC. Results of pretreatment studies indicate that auranofin's inhibitory activity of PMNADCC is caused by a noncytotoxic effect on PMN function which is not associated with alteration of PMN-target cell contact. In contrast to its inhibitory activity on PMNADCC, auranofin pretreatment of mononuclear cells resulted in enhanced target cell destruction which appeared to correlate with increased mononuclear cell-target cell contact.
Insights
Auranofin inhibits antibody-dependent cellular cytotoxicity (ADCC) mediated by neutrophils but enhances it when mediated by mononuclear cells. This suggests differential effects of gold compounds on immune cell functions.
Area of Science:
- Immunology
- Pharmacology
Background:
- Antibody-dependent cellular cytotoxicity (ADCC) is a key immune mechanism.
- Gold compounds are used clinically, but their immunomodulatory effects require further investigation.
Purpose of the Study:
- To investigate the in vitro effects of auranofin and other gold compounds on ADCC.
- To determine the impact of these compounds on different immune cell types.
Main Methods:
- In vitro evaluation of auranofin, gold sodium thiomalate, and gold thioglucose on ADCC.
- Assessment of effects on peripheral blood polymorphonuclear neutrophils (PMNs) and mononuclear cells from rats.
- Pretreatment studies to elucidate mechanisms of action.
Main Results:
- Auranofin (10 microM) potently inhibited PMN-mediated ADCC.
- Gold sodium thiomalate and gold thioglucose showed no inhibition of PMN-ADCC.
- Low concentrations of auranofin and gold sodium thiomalate enhanced PMN-ADCC in continuous culture.
- Auranofin inhibited PMN-ADCC via a noncytotoxic effect on PMN function.
- Auranofin enhanced mononuclear cell-mediated target cell destruction, correlating with increased cell contact.
Conclusions:
- Auranofin exhibits differential immunomodulatory effects, inhibiting PMN-ADCC while enhancing mononuclear cell-mediated cytotoxicity.
- The mechanism of auranofin's inhibition of PMN-ADCC involves PMN function rather than cell contact.
- These findings highlight the complex interactions between gold compounds and immune cells, with implications for their therapeutic use.
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