IMMUNOELECTRON MICROSCOPY OF THE GLOMERULAR MESANGIAL UPTAKE AND TRANSPORT OF AGGREGATED HUMAN-ALBUMIN IN THE MOUSE

Abstract

The uptake and disposal of injected aggregated human albumin (AHA) by the gomerular mesangium of normal mice was evaluated by immunoelectron microscopy. The injected AHA rapidly entered the mesangial matrix channels via endothelial fenestra at the axial pole of the lobules and reached maximal concentrations at 8 h after injection. Small quantities of AHA were endocytosed by mesangial cells. Significant filtration of the polydispersed AHA, which included molecular albumin, was observed across both the peripheral glomerular basement membrane and the mesangial glomerular basement membrane. The injected AHA was observed in the juxtaglomerular region, between lacis cells and in the wall of arterioles at early time periods after injection. A heavy fraction of AHA (MW, > 1 million) was also readily taken up by the mesangium but was not filtered. The heavy AHA was also transported to the juxtaglomerular region and was found in the interstitial space in the vicinity of glomeruli at 2 1/2 h after injection. A method is shown for sequential study of the distribution in the kidney of protein macromolecules of great biologic significance. The ultrastructural features of the processing of protein aggregates is similar to that of several previously studied electron-dense tracer macromolecules. An efferent limb of mesangial drainage to the region of the juxtaglomerular region and the renal interstitium appears to exist. Very large aggregates readily transited this pathway and were found in the interstitial space; the renal lymphatics may participate in the clearance of macromolecules from the glomerular mesangium.