Effect of dextrans of various molecular weights on mesangial transport in ddY mice pretreated with sheep anti-type IV collagen serum.

The authors' previous report concluded that increased mesangial IgA deposition seen in ddY mice pretreated with mesangiotropic anti-type IV collagen serum might be due to a dysfunction of mesangial transport of macromolecules such as polymeric autologous IgA. In the present study we examined the effect of macromolecules upon mesangial transport in similarly treated ddY mice, using intravenously administered FITC-labeled dextrans of various molecular weights as tracers. The intensity of each resulting mesangial dextran deposit inspected directly by immunofluorescence was measured periodically and compared with the deposition of autologous mouse IgA examined using rhodamine-labeled rabbit anti-mouse IgA. High-molecular-weight dextran of 2,000 kDa showed prolonged mesangial deposition which paralleled the intensity and distribution of the autologous mouse IgA deposition. In contrast, medium- and low-molecular-weight dextrans of 500 and 150 kDa, respectively, disappeared earlier from the mesangium, unlike the autologous IgA deposition which persisted. Based on these results, it was concluded that the macromolecularity of certain substances and a transport dysfunction of the mesangium may both be major factors in prolonged mesangial deposition. These findings may provide some clues to help clarify the pathogenesis of human IgA nephritis.