Experimental model of focal sclerosis. II. Correlation with immunopathologic changes, macromolecular kinetics, and polyanion loss

J. A. Velosa, R. J. Glasser, T. E. Nevins, A. F. Michael

Research output: Contribution to journalArticlepeer-review

94 Scopus citations

Abstract

In a model of focal sclerosis induced by aminonucleoside administration to the rat, renal tissues were studied by immunofluorescence with respect to immunoprotein deposition and aggregated human IgG uptake. Glomerular polyanion, a negatively charged sialoprotein, was evaluated by colloidal iron staining. After an initial aminonucleoside dose, polyanion loss (PL) was demonstrated (7 and 14 days), associated with proteinuria, and was followed by recovery of polyanion (25 days) with reduction of proteinuria to normal levels. After a second aminonucleoside administration, focal sclerosis developed (52 and 75 days) and the following correlations were established: the pattern of immunoprotein deposition and PL was focal and segmental; the percentage of glomeruli with sclerosis was less than the percentage containing IgM and fibrin-related antigens (FRA) and was similar to the percentage with PL; there was a correspondence between the loci of focal sclerosis, IgM and FRA localization, and areas of PL; a direct correlation existed between PL and total urinary protein excretion (r = 0.83). Dual label immunofluorescence demonstrated IgM and FRA together in capillary walls and mesangium, FRA alone in extramembranous localization, and antihemophilic factor predominantly in capillary walls. Aggregated human IgG uptake evaluated 12, 24, and 72 hr after injection showed accumulation and persistence in the areas undergoing sclerosis. Irreversible epithelial cell injury may be the primary pathogenetic mechanism leading to proteinuria, FRA deposition, synechia, collapse of capillary loops, accumulation of protein aggregates in the mesangium and subendothelium, and focal sclerosis.

Original languageEnglish (US)
Pages (from-to)527-534
Number of pages8
JournalLaboratory Investigation
Volume36
Issue number5
StatePublished - Dec 1 1977

Fingerprint Dive into the research topics of 'Experimental model of focal sclerosis. II. Correlation with immunopathologic changes, macromolecular kinetics, and polyanion loss'. Together they form a unique fingerprint.

Cite this