Periglomerular accumulation of dendritic cells in rat crescentic glomerulonephritis.
BACKGROUND
An increased number of major histocompatibility complex (MHC) class II-positive cells (OX-6+ cells) were observed in the glomerulus and periglomerular interstitium during the course of anti-glomerular basement membrane (anti-GBM) crescentic glomerulonephritis (GN) in WKY rats. This study aimed to demonstrate that periglomerular OX-6+ cells are dendritic cells (DCs) and to clarify their roles in the pathogenesis of this GN.


METHODS
Kidney sections were stained with the OX-6 and the rat DC marker OX-62 by immunohistochemistry, and periglomerular OX-6+ cells were observed by immunoelectron microscopy. Renal mRNA expression for CXCL12 was examined by reverse transcriptase polymerase chain reaction (RT-PCR) and in situ hybridization, and that for IL-1beta was examined by in situ hybridization.


RESULTS
Immunohistochemistry revealed that most periglomerular OX-6+ cells in this GN were ED-1-negative. OX-62+ cells were observed sparsely in normal kidney interstitium, and considerably more frequently in periglomerular interstitium in this GN. Immunoelectron microscopy confirmed the periglomerular OX-6+ED-1- cells had DC morphology. The increased expression of CXCL12 mRNA in the diseased glomerulus was shown by RT-PCR. By in situ hybridization, CXCL12 mRNA-expressing glomerular cells were the parietal and visceral epithelial cells, which were close to the site of periglomerular OX-6+ cell localization. The intense expression of IL-1beta mRNA by periglomerular cells was demonstrated by in situ hybridization.


CONCLUSIONS
The periglomerular distribution of OX-6+ED-1- DCs was demonstrated in anti-GBM crescentic GN in WKY rats. These DCs might be accumulated in periglomerular interstitium by CXCL12, and play a role in the initiation and progression of this GN by producing IL-1beta.
Fujinaka
Hidehiko
H
Department of Structural Pathology, Institute of Nephrology, Niigata University Graduate School of Medical and Dental Sciences, Niigata - Japan. dext007@hotmail.com
Nameta
Masaaki
M
Kovalenko
Pavel
P
Matsuki
Asako
A
Kato
Nobutaka
N
Nishimoto
Goro
G
Yoshida
Yutaka
Y
Yaoita
Eishin
E
Naito
Makoto
M
Kihara
Itaru
I
Tomizawa
Shuichi
S
Yamamoto
Tadashi
T
D000818:Animals; D003713:Dendritic Cells; D005921:Glomerulonephritis / Q000473:pathology*; D007678:Kidney Glomerulus; D051381:Rats; D011921:Rats, Inbred WKY