Effect of morphine on uptake of immunoglobulin G complexes by mesangial cells and macrophages

Focal glomerular sclerosis is the predominant renal lesion in heroin addicts. We studied whether morphine, a metabolite of heroin, could directly affect the uptake of immunoglobulin G (IgG) complexes by cultured mesangial cells (MC) and macrophages (MP). Preincubation of morphine (10^-6 M) decreased uptake of IgG complexes [morphine, 66,577 ± 6,248 vs. control, 95,735 ± 5,227 counts·min^-1 (cpm)·mg protein^-1; P < 0.02] by MC. Morphine (10^-4-10^-6 M) also inhibited (P < 0.01) uptake of 1,1′-dioctadecyl-3,3,3′,3′-tetramethyl-indocarbocyanine perchlorate-labeled low-density lipoprotein by MC. MP pretreated with morphine (10^-6 M) also showed significantly (P < 0.02) lower uptake of IgG complexes (control, 94,959 ± 4,980 vs. morphine, 58,360 ± 11,608 cpm/mg protein). Binding studies carried out at 4°C on MC and MP indicated that morphine did not modulate surface binding of IgG complexes. Naloxone, a morphine antagonist, also produced a rather decreased (P < 0.05) uptake of IgG complexes by both MP and MC and did not inhibit the effect of morphine on the uptake of IgG complexes. In vivo studies indicated that morphine-treated rats had a higher (P < 0.05) accumulation of aggregated human IgG complexes (¹²⁵I-labeled ahIgG) in their glomeruli when compared with untreated rats (control rats, 256,929 ± 40,008 cpm/g protein vs. experimental rats, 398,317 + 51,512 cpm/g). Increased accumulation of ¹²⁵I-ahIgG in the glomeruli from morphine-treated rats may either be related to increased delivery of ¹²⁵I-ahIgG into the mesangium or be a result of decreased drainage of ¹²⁵I-ahIgG from the mesangium. In the mesangium, too, the effect of morphine on MC and MP may attenuate uptake of these macromolecules and may thus alter the quality and quantity of the mesangial matrix.