Role of macrophages in the glomerular mesangial uptake of polyvinyl alcohol in rats.

Glomerular mesangial cell populations were characterized through sequential morphologic studies after injection of polyvinyl alcohol (PVA), a synthetic polysaccharide previously shown to accumulate in the mesangium. Renal tissue was obtained from groups of rats, 1 day to 28 days after initial subcutaneous injection of PVA, and studied by transmission electron microscopy and fluorescence microscopy using monoclonal antibodies to rat Ia. PVA was initially present in areas of attenuated mesangial matrix. Subsequently, only a small fraction of PVA was associated with "classical" mesangial cells. By 3 days, variable degrees of glomerular hypercellularity were noted, and PVA appeared within phagocytic vacuoles of immature macrophages in the mesangium and in occasional endocytic vacuoles of endothelial and mesangial cells. At later time points, increasing quantities of PVA were found within the large confluent phagolysosomes of more mature mesangial macrophages. By 2 weeks, features of epithelioid transformation were evident. By 3 and 4 weeks many glomeruli contained several mesangial microgranulomas, i.e., collections of epithelioid cells of variable degree of maturation, including giant cells. An increase in Ia-positive cells in glomeruli corresponded closely to the increase in numbers of cells with ultrastructural characteristics of macrophages and epithelioid cells within mesangial regions. These studies demonstrate a primary role for macrophages in the uptake of PVA, a process ultimately leading to granuloma formation in the mesangium.