Morphine-induced macrophage activity modulates mesangial cell proliferation and matrix synthesis

Abstract

Glomerular mesangial injury is the predominant renal lesion in patients with heroin addiction. We studied the effect of morphine (an active metabolite of heroin) activated macrophages on mesangial cell (MC) proliferation and matrix synthesis. We prepared conditioned media containing either vehicle alone (CSP), macrophage secretory products (MSP) and secretory products of morphine treated macrophages (M-MSP). M-MSP increased (P < 0.01) the proliferation of MC when compared with MSP alone. M-MSP increased synthesis of laminin by MC at concentrations of 10 to 50% when compared with cells treated with MSP alone (at 50% concentration, MSP, 126 ± 19 vs. M-MSP, 312 ± 14 ng/mg protein, P < 0.001). M-MSP also increased the synthesis of collagen type IV by MC. This effect of M-MSP was attenuated (P < 0.05) by anti-TGF-β antibodies. Since M-MSP also increased mRNA expression for TGF-β by MC, it appears that the effect of M-MSP on MC may be mediated through the generation of TGF-β.