Ultrastructural localization of anionic and cationic ferritin in the rat glomerular basement membrane in protein‐overload proteinuria

Abstract

The penetration into the glomerular basement membrane of anionic and cationic ferritin has been studied in rats made proteinuric by intraperitoneal administration of bovine serum albumin. In comparison with control animals anionic ferritin penetrated the glomerular basement membrane to a much greater extent in proteinuric rats. Some ferritin particles were observed in small invaginations of the epithelial cell membrane adjacent to the glomerular basement membrane and incorporated in pinocytotic vesicles within the epithelial cell cytoplasm. This was not seen in control animals. Cationic ferritin distribution in the glomerular basement membrane was similar in control and proteinuric rats suggesting that the increased anionic ferritin penetration observed occurs without any reduction in fixed anionic charge.

Podocyte is the major culprit accounting for the progression of chronic renal disease

“…Evidence for the rupture of lysosomal elements, spillage of lysosomal enzymes, and subsequent dissolution of such a podocyte has also been presented previously (Shirato et al, 1996). Moreover, as seen in our studies and in those from others (Farquhar and Palade, 1961;Bliss and Brewer, 1984), podocytes filled with lysosomal elements consistently display additional injuries, such as foot process effacement and formation of pseudocysts.…”

“…Since the classic experimental study by Farquhar and Palade (1961), podocytes densely filled with absorption granules have been encountered in many experimental glomerular diseases, including all models of FSGS (Kretzler et al, 1994;Kriz et al, 1995Kriz et al, , 1998aShirato et al, 1996;Bliss and Brewer, 1984) and are well known in the pathology of human cases. Evidence for the rupture of lysosomal elements, spillage of lysosomal enzymes, and subsequent dissolution of such a podocyte has also been presented previously (Shirato et al, 1996).…”

Immunocytochemical investigation of the in vivo endocytosis by renal tubular epithelial cells

“…Upon introduction into the circulation, the cationized BSA-DNP was filtered at the level of the glomerular wall and was found to bind to the laminae rarae interna and externa as previously shown for this and other cationic probes (Bliss and Brewer, 1984;Cohen et al, 1983;Kanwar and Farquhar, 1979;Rennke and Venkatachalam, 1977). Such a pattern reflects the distribution of GBM anionic charges (Kanwar and Farquhar, 1979;Russo et al, 1993).…”

Progression of chronic renal failure in focal segmental glomerulosclerosis: consequence of podocyte damage or of tubulointerstitial fibrosis?

“…The degenerative process, again as indicated by the name, starts in the glomerulus as a segmental injury that may proceed to global sclerosis and loss of the entire nephron. In animal models mimicking the histopathology of human FSGS [1,2,3,4,5,6,7], the committed lesion initiating the segmental injury has been shown to consist of the formation of a tuft adhesion to Bowman's capsule (BC). As shown in these studies, the degeneration of a nephron occurs according to the following sequence of events which crucially involves the podocyte.…”

“…Within a list of possible factors damaging a podocyte under the conditions of FSGS development, an exuberant lysosomal uptake of proteins passing through a nearby damaged filter A [42,43] is ranked prominently. Since the classic experimental study by Farquhar and Palade in 1961 [44], podocytes densely filled with absorption granules have been encountered in many experimental glomerular diseases, including all models of FSGS [3,5,6,7,43,45], and are well known in the pathology of human cases. Evidence for the rupture of lysosomal elements, spillage of lysosomal enzymes and subsequent dissolution of such podocytes has also been presented previously [43].…”