Morphine modulates mesangial immunoglobulin G uptake in rats with antithymocyte serum-induced mesangial cell injury

The glomerular mesangium is an important site of activity in patients with heroin addiction. We studied the effect of morphine, a metabolite of heroin, on the mesangial immunoglobulin G aggregate uptake in a model of specific mesangial cell injury. Isolated specific mesangial cell injury was developed in Lewis rats by injecting intravenously antithymocyte serum (ATS). Forty-eight hours later, radioiodinated, heat aggregated immunoglobulin G (AHIgG(125)I) was administered (20 mg/100 g i.v.) by tail vein. At 4 and 24 h, kidneys, liver, and spleen were removed, glomeruli isolated, and the radioactivity measured. Blood levels of AHIgG(125)I were measured at 0, 4 and 24 h. For ultrastructural studies, IgG-coated gold particles were injected, and the mesangial circulation was studied. At 4 h, ATS-treated rats showed a lower (p < 0.02) accumulation of AHIgG(125)I in the mesangium when compared with control rats (controls 511,012 +/- 10,807 vs. ATS 464,614 +/- 7,944 cpm/g glomerular protein). ATS plus morphine treated rats showed a higher (p < 0.01) accumulation of AHIgG(125)I when compared with rats treated with ATS alone. Even at 24 h, morphine-treated ATS rats showed a higher accumulation of AHIgG(125)I when compared with those treated with ATS alone. Ultrastructural studies showed aggregation of IgG-coated gold particles in the mesangial cell endolysosomes of control rats. Our results suggest that macromolecules may dwell longer in the mesangium of rats with intact mesangial cells. This increase in transit time may be related to the uptake of these macromolecules by mesangial cells. Morphine seems to enhance the accumulation of macromolecules in the mesangium, independent of its action on mesangial cells.