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

Abstract

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). Pre-incubation 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 degrees 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.(ABSTRACT TRUNCATED AT 250 WORDS)