title: Morphine modulates migration of monocytes.
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.
authors.affiliation: Department of Medicine, Long Island Jewish Medical Center, New Hyde Park, N.Y. 11040, USA.
authors.forename: P C
authors.initials: PC
authors.lastname: Singhal
authors.forename: Z
authors.initials: Z
authors.lastname: Shan
authors.forename: P
authors.initials: P
authors.lastname: Garg
authors.forename: K
authors.initials: K
authors.lastname: Sharma
authors.forename: P
authors.initials: P
authors.lastname: Sharma
authors.forename: N
authors.initials: N
authors.lastname: Gibbons
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D002450:Cell Communication / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000494:pharmacology; D017077:Culture Media, Conditioned; D016166:Free Radical Scavengers / Q000494:pharmacology; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects / Q000648:ultrastructure; D051379:Mice; D008855:Microscopy, Electron, Scanning; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D009020:Morphine / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D013481:Superoxides / Q000378:metabolism; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D018932:Chemokine CCL2; D017077:Culture Media, Conditioned; D016166:Free Radical Scavengers; D009294:Narcotics; D012333:RNA, Messenger; D013481:Superoxides; D009020:Morphine; C038983:1,3-dimethylthiourea; D013890:Thiourea