AMYLOID-A (AA) FIBRIL FORMATION IN RENAL TUBULES OCCURS INTRACYTOPLASMICALLY, POSSIBLY AT THE SITE OF MEMBRANE ASSEMBLING STRUCTURES

Immunoelectron microscopy with anti-AA antibodies was used to study ca sein induced renal amyloidosis in mice. Amyloid deposits were distribu ted mainly in the peritubular or perivascular interstitium of the oute r zone of the medulla and papillary tip, and to a lesser degree in the inner zone of the medulla, cortex and glomeruli. Invaginated pits fro m the basal cytoplasmic membrane of collecting tubules, thin segments of Henle's loop and proximal tubules reacted with anti-AA antibodies. The part of the membrane of cytoplasmic vesicles that contained amyloi d fibrils was patchily stained in the thin segment of Henle's loop. Cu rious anti-AA positive membrane assembling structures (MAS), which wer e composed of twisted membranes,filaments or elongated vesicles, were detected in the cytoplasm of the proximal and collecting tubules. Thes e MAS were associated with the pits of the plasma membrane and were un detectable by conventional electron microscopy. In the interstitial ca pillaries, endothelial pits facing the exterior contained bundles of a myloid fibrils. The findings suggest that tubular epithelia and inters titial endothelia play a role in amyloid fibrillogenesis in the kidney . In the tubular cytoplasm, reabsorbed SAA appears to form MAS which f use with the basal plasma membrane and presumably then release complet e amyloid fibrils extracellularly. Thus, amyloid fibrillogenesis may t ake place on the intracytoplasmic membranes in renal tubules.