Role of intrinsic renal cells versus infiltrating cells in glomerular crescent formation.
BACKGROUND
Studies were undertaken to characterize the cellular composition that occurs in glomeruli and the tubulointerstitium of a passive model of complement-independent crescentic nephritis in mice.


METHODS
Glomerulonephritis was induced by the injection of antibody to whole rabbit glomeruli, and tissue was examined histologically at 7, 14 and 28 days.


RESULTS
Mice developed proteinuria, glomerular crescents, and progressive glomerulosclerosis and tubulointerstitial fibrosis. The majority of the cells within the crescents appeared to be intrinsic ezrin-positive epithelial cells of visceral or parietal origin. Many of the ezrin positive cells were proliferating and expressing the PDGF receptor. Despite expression of the macrophage adhesive protein, osteopontin, the early crescents were devoid of infiltrating macrophages, T cells or myofibroblasts, which could be explained by the finding that the Bowman's capsule remained intact. Tubulointerstitial damage also occurred, and included tubular dilation and atrophy, periglomerular and patchy interstitial infiltration and interstitial fibrosis with increased interstitial deposition of type IV collagen and laminin. Interstitial infiltrating cells included macrophages, CD4+ T lymphocytes, CD8+ T lymphocytes, and activated myofibroblasts. Tubular osteopontin expression was increased in the areas of tubulointerstitial damage and was associated with interstitial macrophage infiltration.


CONCLUSIONS
We describe an experimental model of complement-independent murine crescentic nephritis associated with tubulointerstitial injury. Proliferating glomerular epithelial cells are the main cellular components of the crescents in this model.
Department of Medicine, University of Washington School of Medicine, Seattle, USA.
V
V
Ophascharoensuk
J W
JW
Pippin
K L
KL
Gordon
S J
SJ
Shankland
W G
WG
Couser
R J
RJ
Johnson
D000818:Animals; D002455:Cell Division; D004847:Epithelial Cells / Q000473:pathology; D005455:Fluorescent Antibody Technique; D005921:Glomerulonephritis / Q000209:etiology*; D007678:Kidney Glomerulus / Q000473:pathology*; D007684:Kidney Tubules / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D053495:Osteopontin; D011817:Rabbits; D012756:Sheep; D012795:Sialoglycoproteins / Q000096:biosynthesis
D012795:Sialoglycoproteins; C506896:Spp1 protein, mouse; D053495:Osteopontin