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Humoral immune processes mediate alterations in glomerular basement membrane (GBM) permeability by two mechanisms. One requires complement and polymorphonuclear leukocytes and the second is complement- and polymorphonuclear leukocyte-independent. The structural basis for enhanced GBM permeability induced by anti-GBM antibody is not clear. Experimental anti-GBM glomerulopathy was induced in guinea pigs by immunization with human GBM in complete Freund's adjuvant. Control animals received injections of complete Freund's adjuvant alone. Light, immunofluorescent, and electron microscopic studies were done on eight heavily proteinuric animals, four immunized nonproteinuric animals, three controls, and two normal animals. All animals that received injections of GBM had intense linear deposits of gamma2 anti-GBM antibody. Complement deposition was not demonstrable in vivo, and anti-GBM antibody deposits did not fix complement in vitro. Histologic abnormalities in proteinuric animals were confined to the GBM, which was of variable density and had a characteristic beaded thickening, with numerous areas of electron lucency most prominent in the outer aspect of GBM in peripheral portions of capillary loops. The inner margin and endothelium were normal. Ultrastructural tracer studies with ferritin demonstrated increased permeability confined to portions of GBM demonstrating ultrastructural lesions. The urine protein excreted by animals with ultrastructural GBM lesions was largely albumin. The absence of complement deposition accompanying anti-GBM antibody deposits in vivo and the unique GBM lesion in this model differ from the findings in nephritis induced by most heterologous nephrotoxic antibodies and suggest that GBM injury in this model is mediated by autologous antibody through complement-independent mechanisms. The selective proteinuria and ultrastructural lesions suggest a derangement in glomerular permeability functionally localized to the epithelial side of the GBM and could reflect an antibody-mediated abnormality in GBM biosynthesis.
W G Couser, and
B H Spargo, and
M M Stilmant, and
E J Lewis
August 1973,
Laboratory investigation; a journal of technical methods and pathology,
W G Couser, and
B H Spargo, and
M M Stilmant, and
E J Lewis
January 2013,
Journal of veterinary science,
W G Couser, and
B H Spargo, and
M M Stilmant, and
E J Lewis
October 1974,
British medical journal,
W G Couser, and
B H Spargo, and
M M Stilmant, and
E J Lewis
June 1976,
The American journal of pathology,
W G Couser, and
B H Spargo, and
M M Stilmant, and
E J Lewis
January 1986,
American journal of kidney diseases : the official journal of the National Kidney Foundation,
W G Couser, and
B H Spargo, and
M M Stilmant, and
E J Lewis
September 1977,
Veterinary pathology,
W G Couser, and
B H Spargo, and
M M Stilmant, and
E J Lewis
January 1974,
Advances in nephrology from the Necker Hospital,
W G Couser, and
B H Spargo, and
M M Stilmant, and
E J Lewis
January 1994,
The Journal of clinical investigation,
W G Couser, and
B H Spargo, and
M M Stilmant, and
E J Lewis
May 2007,
Journal of comparative pathology,
W G Couser, and
B H Spargo, and
M M Stilmant, and
E J Lewis
June 1966,
Die Naturwissenschaften,
