Studies of glomerular mesangial uptake and processing of macromolecules. I. Effect of polyvinyl alcohol-induced macrophages on uptake of iron dextran.

The influence of prior glomerular mesangial uptake of a macromolecule that induces the infiltration of macrophages (M phi) into the mesangium on the uptake of a second macromolecule by the mesangium was studied in inbred Lewis rats. Renal transplantation of kidneys from rats previously injected with polyvinyl alcohol (PVA) was performed to avoid the potential influences of ongoing uptake of PVA and altered host milieu on the glomerular uptake of iron dextran (ID), a macromolecule that localizes primarily in the intrinsic mesangial cells of unmodified rats. In contrast to that in the recipient's native kidney, the uptake of ID was markedly increased in the glomeruli in kidneys previously exposed to PVA. This enhanced uptake was the consequence of the phagocytic activity of mesangial M phi elicited by and containing PVA since the site of increased ID content was shown by ultrastructural studies to be within mesangial M phi. Isogeneic renal transplantation per se did not influence mesangial function since the glomerular uptake of ID in donor and recipient kidneys was the same when donors were normal rats. In addition to the enhanced uptake of ID into lysosomes by mesangial M phi these cells were also much more active in the further processing of ID to ferritin particles within the cytoplasm than were intrinsic mesangial cells. These studies demonstrate that M phi attracted to the mesangium by a stimulus such as PVA may have important effects on the consequences of additional challenges to the mesangium.