Quantitation of the intrarenal uptake of immunoglobulin aggregates by macrophages in diffuse proliferative...

The intrarenal processing of circulating immune-complex-like-material is traditionally attributed to resident glomerular mesangial cells. To assess the contribution of infiltrating mononuclear cells to macromolecule processing by diseased glomeruli we have utilized an isolated perfused kidney system (IPK) to quantify the specific glomerular uptake of heat-aggregated immunoglobulin (AIgG) (as micrograms of aggregated IgG per 10(4) glomeruli (microgram 10(4)glom)). Mononuclear cell infiltrated glomeruli from animals with diffuse proliferative glomerulonephritis had a significantly augmented uptake of AIgG (48.9 +/- 3.8 micrograms/10(4)glom; normal 11.8 +/- 0.6 micrograms/10(4)glom; P less than 0.01). Specific blockade of mononuclear cell function by perfusion with anti-macrophage-serum (AMS) prevented increased AIgG uptake (12.8 +/- 1.2 micrograms/10(4)gloms; P less than 0.01), but had no effect on the AIgG uptake of normal kidneys (13.1 +/- 1.2 micrograms/10(4)glom). Thus, in diffuse proliferative glomerulonephritis the observed increase in the glomerular clearance of AIgG was due to phagocytosis by mononuclear cells. This study suggests that infiltrating, bone-marrow derived mononuclear cells may significantly contribute to the glomerular handling of circulating immune complexes by nephritic glomeruli.