MORPHINE MODULATES MIGRATION OF MONOCYTES

Macrophages seem to play an important role in the development of glome rulosclerosis. In the present study we evaluated the effect of morphin e, an active metabolite of heroin, on the migration of monocytes acros s a filter in a modified Boyden chamber. Morphine-mesangial cell inter action enhanced (p< 0.004) the migration of monocytes across the filte r (control 14.2 +/- 0.6 vs. morphine 22.1 +/- 1.7 monocytes/HPF). Dime thylthiourea (DMTU), a free radical scavenger, attenuated this effect of morphine. Morphine-monocyte secretory products (MMSP) did not modul ate the migration of monocytes. However, the products of interaction b etween mesangial cells and MMSP enhanced (p < 0.001) the passage of mo nocytes across the filter. Mesangial cells treated with MMSP showed mR NA expression for monocyte chemoattractant peptide-1 (MCP-1). Superoxi de also induced mRNA expression for MCP-1 on MC. DMTU attenuated this effect of superoxide. Since morphine activates MC to produce superoxid e and DMTU attenuated the effect of superoxide on MC, the effect of mo rphine on the migration of macrophages may be mediated through superox ide-induced generation of MCP-1. We conclude that morphine enhances th e migration of monocytes. This effect of morphine may be contributing to the development of glomerulosclerosis in patients with heroin addic tion.