Peritubular capillary injury during the progression of experimental glomerulonephritis in rats.
The functional and morphologic changes occurring in the peritubular capillaries (PTC) of the kidney during the progression of renal disease are not yet completely understood. In this study, the features of PTC disruption observed in a rat anti-glomerular basement membrane-induced glomerulonephritis (GN) model were characterized. Contributions to the progression of the disease made by other interstitial components, including ED-1-positive macrophages and CD3-positive T cells, were also investigated. Within 7 d of inducing GN, severe necrotizing glomerular injuries were observed. Thrombomodulin staining revealed that within 3 to 8 wk, there was a significant (P < 0.001) decline in the number of PTC, accompanied by a marked accumulation of macrophages, T cells, and fibrotic material. By the end of this period, most PTC were severely damaged or lost, and tubulointerstitial scarring was noted in the affected areas. Furthermore, PTC endothelial cell apoptosis occurred concomitantly, as shown by application of terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling methods and electron microscopy. It was presumed that the PTC injury was mediated possibly by the infiltrating macrophages and T cells, which, together with destruction of the PTC structure, correlated significantly with the impairment of renal function. These findings suggest that PTC disruption and the subsequent regression of the capillary network may contribute to the development of the tubulointerstitial injury largely responsible for the renal dysfunction in progressive GN.
Ohashi
Ryuji
R
Department of Pathology, Nippon Medical School, Tokyo, Japan.
Kitamura
Hiroshi
H
Department of Pathology, Nippon Medical School, Tokyo, Japan.
Yamanaka
Nobuaki
N
Department of Pathology, Nippon Medical School, Tokyo, Japan.
D000818:Animals; D002196:Capillaries / Q000473:pathology*; D016923:Cell Death; D004195:Disease Models, Animal; D018450:Disease Progression; D005921:Glomerulonephritis / Q000473:pathology* / Q000503:physiopathology; D007677:Kidney Function Tests; D007684:Kidney Tubules / Q000098:blood supply* / Q000293:injuries; D008297:Male; D051381:Rats; D011921:Rats, Inbred WKY; D018709:Statistics, Nonparametric