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Potential immunomodulatory activity of phenylphosphonothioates
S B Pruett1, J E Chambers, H W Chambers
1Department of Biological Sciences, Mississippi State University, Mississippi State 39762.
International Journal of Immunopharmacology
|January 1, 1989
Summary
Certain organophosphorous compounds, specifically phenylphosphonothioates, enhance lymphocyte activation similarly to 2-mercaptoethanol (2-ME). These compounds support lymphocyte growth and survival, suggesting a comparable mechanism of action with low toxicity.
Area of Science:
- Immunotoxicology
- Biochemistry
Background:
- Organophosphorous compounds are known for their immunotoxicological effects.
- Phenylphosphonothioates were observed to enhance rat splenocyte activation by concanavalin A.
- 2-mercaptoethanol (2-ME) is a well-characterized immunomodulatory thiol.
Purpose of the Study:
- To compare the immunomodulatory effects of phenylphosphonothioates with 2-mercaptoethanol (2-ME).
- To investigate the mechanism of action of these compounds on lymphocyte cell lines and splenocytes.
- To assess the in vitro and in vivo toxicity of a low neurotoxic potential phosphonothioate.
Main Methods:
- Comparison of phenylphosphonothioates and 2-ME on CTLL-2 cell growth.
- Assessment of additive effects on CTLL-2 cells and rat splenocytes.
- Measurement of interleukin-2 production in mitogen-stimulated splenocytes.
- Evaluation of cell survival and cystine incorporation by CTLL-2 cells.
- Analysis of extracellular thiol generation.
- In vitro lymphocyte growth support and in vivo acute toxicity testing in mice.
Main Results:
- Two phenylphosphonothioates substituted for 2-ME, enabling near-maximal growth of the 2-ME-dependent CTLL-2 cell line.
- These compounds showed additive effects with 2-ME on CTLL-2 cells and rat splenocytes.
- Phosphonothioates did not significantly affect interleukin-2 production.
- One phosphonothioate and its hydrolysis product supported CTLL-2 cell survival and enhanced cystine incorporation.
- 2-ME was more effective in stimulating extracellular thiol generation compared to the other agents.
- A low neurotoxic phosphonothioate effectively supported lymphocyte growth in vitro and demonstrated low acute toxicity in mice.
Conclusions:
- Phenylphosphonothioates share similar mechanisms of action with 2-mercaptoethanol (2-ME) in modulating lymphocyte responses.
- These compounds can support lymphocyte growth and survival, indicating potential as immunomodulatory agents.
- The examined phosphonothioate exhibits favorable toxicity profiles, suggesting potential for further investigation.