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The accumulation of [35S]methimazole by monocytes and macrophages
Abstract:
We have used an automatic cell harvester and micro culture techniques to examine the accumulation of [35S]methimazole by monocytes, macrophages and lymphocytes. Significant temperature-dependent accumulation of the drug was found in resting monocytes and macrophages; this was increased up to 4-fold by phagocytosis. Lymphocytes accumulated little or no drug and myeloma and leukaemic cell lines accumulated none. These results show that two interrelated cells with endogenous peroxidatic activity take up the antithyroid drug methimazole providing further support for the concept that immunosuppression by this drug in Graves' disease is mediated via an action on antigen-presenting cells.
Insights
The antithyroid drug methimazole accumulates in monocytes and macrophages, especially during phagocytosis. This uptake by antigen-presenting cells may explain methimazole's immunosuppressive effects in Graves' disease.
Area of Science:
- Immunology
- Pharmacology
- Cell Biology
Background:
- Graves' disease is an autoimmune disorder often treated with antithyroid drugs.
- Methimazole is a commonly prescribed antithyroid medication.
- The mechanism of immunosuppression by methimazole is not fully understood but may involve antigen-presenting cells.
Purpose of the Study:
- To investigate the cellular accumulation of the antithyroid drug methimazole.
- To determine which immune cells are responsible for methimazole uptake.
- To explore the role of phagocytosis in drug accumulation.
Main Methods:
- Utilized automatic cell harvesters and microculture techniques.
- Quantified the accumulation of radiolabeled [35S]methimazole.
- Examined drug uptake in monocytes, macrophages, lymphocytes, and cell lines.
Main Results:
- Significant temperature-dependent accumulation of methimazole was observed in resting monocytes and macrophages.
- Phagocytosis increased methimazole accumulation in these cells by up to 4-fold.
- Lymphocytes, myeloma, and leukaemic cell lines showed little to no drug accumulation.
Conclusions:
- Monocytes and macrophages, cells with endogenous peroxidatic activity, actively take up methimazole.
- These findings support the hypothesis that methimazole's immunosuppressive effects in Graves' disease are mediated through its action on antigen-presenting cells.