title: Experimental glomerular endothelial injury in vivo.
abstract: The microvascular endothelium of the kidney glomerulus is injured in Shiga-like toxigenic bacterial infection, genetic or acquired loss of complement regulatory protein function, and allo-immune responses of solid-organ or bone marrow transplantation. Existing models of diseases with glomerular endothelial cell (EC) injury, collectively grouped as thrombotic microangiopathies, are problematic, impeding investigation of the mechanisms of microvascular defense and repair. To develop a model of glomerular endothelial injury in the mouse, we conjugated the M. oreades lectin to the cytotoxin, saporin, (LS) to selectively injure the glomerular endothelium. Injury of the microvasculature was evaluated by light, immunofluorescence, and electron microscopy, and by quantitative RT-PCR of cell-type specific transcripts. Renal function was evaluated by quantitation of serum creatinine. The toxin conjugate induced apoptosis of microvascular ECs in vitro, and subtle histologic features of thrombotic microangiopathy in vivo that were enhanced by co-injection of 50 μg/kg LPS. Among LS/LPS-treated animals, loss of glomerular EC staining correlated with decreased expression of EC-specific transcripts, and impaired kidney function. Selective injury of the glomerular microvasculature with LS toxin conjugate and LPS elicits histologic features of thrombotic microangiopathy and acute kidney failure.
authors.affiliation: Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: George
authors.initials: G
authors.lastname: Haddad
authors.forename: Lin Fu
authors.initials: LF
authors.lastname: Zhu
authors.forename: David C
authors.initials: DC
authors.lastname: Rayner
authors.forename: Allan G
authors.initials: AG
authors.lastname: Murray
mesh_terms: D000818:Animals; D017209:Apoptosis; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000293:injuries* / Q000382:microbiology / Q000473:pathology; D005260:Female; D005337:Fibrin / Q000378:metabolism; D007678:Kidney Glomerulus / Q000098:blood supply* / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D055806:Microvessels / Q000473:pathology; D051437:Renal Insufficiency / Q000150:complications; D013927:Thrombosis / Q000150:complications
chemical_list: D005337:Fibrin