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Morphine modulates migration of monocytes
1Department of Medicine, Long Island Jewish Medical Center, New Hyde Park, N.Y. 11040, USA.
Abstract:
Macrophages seem to play an important role in the development of glomerulosclerosis. In the present study we evaluated the effect of morphine, an active metabolite of heroin, on the migration of monocytes across a filter in a modified Boyden chamber. Morphine-mesangial cell interaction enhanced (p < 0.004) the migration of monocytes across the filter (control 14.2 +/- 0.6 vs. morphine 22.1 +/- 1.7 monocytes/HPF). Dimethylthiourea (DMTU), a free radical scavenger, attenuated this effect of morphine. Morphine-monocyte secretory products (MMSP) did not modulate the migration of monocytes. However, the products of interaction between mesangial cells and MMSP enhanced (p < 0.001) the passage of monocytes across the filter. Mesangial cells treated with MMSP showed mRNA expression for monocyte chemoat-tractant peptide-1 (MCP-1). Superoxide also induced mRNA expression for MCP-1 on MC. DMTU attenuated this effect of superoxide. Since morphine activates MC to produce superoxide and DMTU attenuated the effect of superoxide on MC, the effect of morphine on the migration of macrophages may be mediated through superoxide-induced generation of MCP-1. We conclude that morphine enhances the migration of monocytes. This effect of morphine may be contributing to the development of glomerulosclerosis in patients with heroin addiction.
Insights
Morphine, a heroin metabolite, significantly increases monocyte migration, potentially contributing to glomerulosclerosis in heroin users. This effect may be linked to superoxide-induced monocyte chemoattractant peptide-1 (MCP-1) generation.
Area of Science:
- Nephrology
- Immunology
- Pharmacology
Background:
- Macrophages are implicated in glomerulosclerosis development.
- Heroin addiction is associated with kidney disease.
- Morphine is an active metabolite of heroin.
Purpose of the Study:
- To investigate the effect of morphine on monocyte migration.
- To explore the role of mesangial cells and free radicals in morphine-induced monocyte migration.
Main Methods:
- Modified Boyden chamber assay to assess monocyte migration.
- Evaluation of dimethylthiourea (DMTU) as a free radical scavenger.
- Analysis of mRNA expression for monocyte chemoattractant peptide-1 (MCP-1).
Main Results:
- Morphine significantly enhanced monocyte migration across filters.
- Dimethylthiourea (DMTU) attenuated the pro-migratory effect of morphine.
- Morphine-activated mesangial cells and their secretory products increased monocyte passage, linked to MCP-1 expression.
Conclusions:
- Morphine promotes monocyte migration, potentially via superoxide-induced MCP-1 generation.
- This mechanism may contribute to glomerulosclerosis in individuals using heroin.
- Further research into morphine's renal effects is warranted.