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Suppression of peritoneal macrophage phagocytosis of Candida albicans by opioids
I Szabo1, M Rojavin, J L Bussiere
1Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, Pennsylvania.
Abstract:
Receptor-selective opioid agonists have been found to suppress the capacity of macrophages to ingest opsonized sheep erythrocytes. In an effort to characterize the immunomodulatory activity of opioids further, experiments were done to examine the uptake of Candida albicans by opioid-treated murine peritoneal macrophages. It was found that treatment with morphine and selective mu, i.e., DAMGO, delta, i.e., DPDPE, and kappa, i.e., trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl) cyclohexyl]benzene-acetamide methanesulfonate, receptor agonists resulted a concentration-dependent suppression of both the percentage of phagocytic cells and the average number of ingested yeasts. Antagonists selective for mu, i.e., H-D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2, delta, i.e., naltrindole, and kappa, i.e., norbinaltorphimine, opioid receptors completely blocked the respective receptor-selective agonist-induced suppression. These results suggest that the mu, delta and kappa opioid receptors can modulate macrophage function.
Insights
Opioid agonists acting on mu, delta, and kappa receptors suppress macrophage ability to engulf Candida albicans. This opioid-mediated immunomodulation of macrophages is reversible with specific opioid receptor antagonists.
Area of Science:
- Immunology
- Pharmacology
- Cell Biology
Background:
- Opioid agonists are known to affect macrophage phagocytosis.
- Further characterization of opioid immunomodulatory activity is needed.
Purpose of the Study:
- To investigate the effect of receptor-selective opioid agonists on macrophage uptake of Candida albicans.
- To determine if mu, delta, and kappa opioid receptors modulate macrophage function.
Main Methods:
- Murine peritoneal macrophages were treated with various opioid receptor agonists (morphine, DAMGO, DPDPE, trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl) cyclohexyl]benzene-acetamide methanesulfonate).
- Phagocytosis of Candida albicans by opioid-treated macrophages was assessed.
- The effect of selective opioid receptor antagonists (H-D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2, naltrindole, norbinaltorphimine) on agonist-induced suppression was evaluated.
Main Results:
- Opioid agonists (morphine, DAMGO, DPDPE, and trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl) cyclohexyl]benzene-acetamide methanesulfonate) caused a concentration-dependent decrease in the percentage of phagocytic macrophages and the number of ingested Candida albicans.
- Selective antagonists for mu, delta, and kappa opioid receptors completely reversed the suppressive effects of their respective agonists.
Conclusions:
- Mu, delta, and kappa opioid receptors play a role in modulating macrophage phagocytic function.
- Opioid receptor signaling pathways are involved in the regulation of immune cell activity.