Effect of morphine on mesangial immunoglobulin G aggregate kinetics

P. C. Singhal, C. Q. Pan, N. Gibbons and E. Valderrama Department of Medicine and Pathology, Long Island Jewish Medical Center, New Hyde Park, New York 11042. Because mesangial expansion is considered a precursor of focal glomerulosclerosis, we studied whether morphine can cause mesangial expansion. We used radiolabeled human immunoglobulin G aggregates (125I-ahIgG) to study mesangial kinetics in control and experimental (morphine-treated) rats. Control and experimental rats were administered 125I-ahIgG by tail vein. Serum levels of 125I-ahIgG and uptake of 125I-ahIgG by liver, spleen, and mesangium were determined at 4, 8, 12, 24, and 36 h after 125I-ahIgG administration. Mesangial 125I-ahIgG levels were higher (P < 0.05) at 4 h and at later periods in morphine-treated vs. control rats. Naloxone, an opioid antagonist, did not attenuate the morphine-induced mesangial accumulation of 125I-ahIgG. The mean uptake of IgG aggregates was lower in the liver and spleen of morphine-treated rats at 36 h (P < 0.05). In both in vivo and in vitro experiments, ultrastructural studies showed accumulation of IgG-coated gold particles in vesicles, endosomes, and lysosomes. Morphine may have increased the accumulation of 125I-ahIgG in the glomeruli either by increasing the delivery of macromolecules into the mesangium or by altering the exit of macromolecules from the mesangium.