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Toxicologic Pathology
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Journal Article

Alterations in Glomerular Anionic Sites in Canine Anti-Glomerular Basement Membrane Nephritis with Onset of Severe Proteinuria

Jiro Sugimoto

Mitsubishi Kasei Corporation, Research Center and Department of Veterinary Pathology, School of Veterinary Medicine, Azabu University

Masahiko Wasaki

Mitsubishi Kasei Corporation, Research Center and Department of Veterinary Pathology, School of Veterinary Medicine, Azabu University

Kinji Shirota

Mitsubishi Kasei Corporation, Research Center and Department of Veterinary Pathology, School of Veterinary Medicine, Azabu University

Yasuo Nomura

Mitsubishi Kasei Corporation, Research Center and Department of Veterinary Pathology, School of Veterinary Medicine, Azabu University

Rabbit anti-glomerular basement membrane serum (AGBM) or normal rabbit serum (NRS) were given intravenously (2 ml/kg body weight) to 8 male beagle dogs. Light and transmission electron microscopy and immunofluorescence were performed on the kidneys on day 7 postinjection. Alterations of anionic sites (ASs) of glomerular basement membrane (GBM) in peripheral, proximal, and paramesangial portions were studied quantitatively by electron microscopy using polyethyleneimine (PEI; molecular weight = 1,800) as a cationic probe. Severe or mild proteinuria developed on day 1 and continued until day 6 postinjection. On day 7 after AGBM injection, the number of PEI granules per 1,000 nm length of the lamina rara externa of GBM in all portions was significantly less than that in NRS-treated dogs (10.48 ± 1.78 versus 14.19 ± 2.35 granules per 1,000 nm of GBM in peripheral portion, 10.81 ± 1.91 versus 14.97 ± 1.35 granules per 1,000 nm of GBM in proximal portion, 8.44 ± 1.76 vs 13.43 ± 2.10 granules per 1,000 nm of GBM in paramesangial portion; p < 0.001). These results indicate that a reduction glomerular AS occurs in AGBM-treated dogs in association with severe or mild proteinuria and alterations in glomerular ASs might play an important role in the pathogenesis of proteinuria in the canine anti-GBM nephritis in addition to morphological changes.

Key Words: Glomerulonephritis • polyethyleneimine

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Toxicologic Pathology, Vol. 22, No. 3, 316-323 (1994)
DOI: 10.1177/019262339402200309
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