Development of progressive glomerulosclerosis in experimental chronic serum sickness.
A rat model of chronic serum sickness was used to study the pathogenesis of progressive glomerulosclerosis complicating experimental immune-complex glomerulonephritis. Chronic serum sickness was induced by immunising rats with bovine serum albumin followed by intraperitoneal administration of the antigen. Early lesions consisted of mesangial deposits of rat immunoglobulins, followed later by transient subendothelial and persistent subepithelial immune aggregates. On the basis of the peak level of proteinuria around day 80, three groups of rats were distinguished: I physiological proteinuria; II 50-500 mg/24 h; and III greater than 500 mg/24 h. The animals were killed at day 220 and the presence of mesangial proliferation, epithelial proliferation, and synechiae, as well as focal glomerulosclerosis was scored. It appeared that all and only proteinuric animals developed progressive glomerulosclerosis, although all three groups of animals passed through a phase with mesangial and subendothelial immune deposits. A strong correlation was found between the degree of proteinuria and the proportion of glomeruli affected. We conclude that the combination of mesangial and subendothelial deposits on the one hand and subepithelial deposits associated with increased protein loss on the other constitute a conditio sine qua non for the development of progressive glomerulosclerosis in this model. The use of specific antibodies to investigate the composition of the sclerotic lesions showed the presence of laminin and type IV collagen, but not of types I and III collagen in sclerotic areas of glomeruli. This indicates that the development of progressive glomerulosclerosis in this model is due to an increased production of glomerular basement membrane components by presumably solely glomerular cells after the occurrence of immunological glomerular injury.
Hogendoorn
P C
PC
Department of Pathology, University of Leiden, The Netherlands.
Bruijn
J A
JA
Gelok
E W
EW
Van den Broek
L J
LJ
Fleuren
G J
GJ
D000818:Animals; D002908:Chronic Disease; D004195:Disease Models, Animal; D005260:Female; D005921:Glomerulonephritis / Q000473:pathology*; D005923:Glomerulosclerosis, Focal Segmental / Q000209:etiology / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D007105:Immune Complex Diseases; D007668:Kidney / Q000276:immunology / Q000473:pathology; D007678:Kidney Glomerulus / Q000276:immunology / Q000473:pathology; D011507:Proteinuria / Q000150:complications / Q000276:immunology; D051381:Rats; D011919:Rats, Inbred Strains; D012713:Serum Sickness / Q000150:complications* / Q000276:immunology / Q000473:pathology