Voltage-gated potassium channel Kv1.3 blocker as a potential treatment for rat anti-glomerular basement membrane glomerulonephritis.
The voltage-gated potassium channel Kv1.3 has been recently identified as a molecular target that allows the selective pharmacological suppression of effector memory T cells (T(EM)) without affecting the function of naïve T cells (T(N)) and central memory T cells (T(CM)). We found that Kv1.3 was expressed on glomeruli and some tubules in rats with anti-glomerular basement membrane glomerulonephritis (anti-GBM GN). A flow cytometry analysis using kidney cells revealed that most of the CD4(+) T cells and some of the CD8(+) T cells had the T(EM) phenotype (CD45RC(-)CD62L(-)). Double immunofluorescence staining using mononuclear cell suspensions isolated from anti-GBM GN kidney showed that Kv1.3 was expressed on T cells and some macrophages. We therefore investigated whether the Kv1.3 blocker Psora-4 can be used to treat anti-GBM GN. Rats that had been given an injection of rabbit anti-rat GBM antibody were also injected with Psora-4 or the vehicle intraperitoneally. Rats given Psora-4 showed less proteinuria and fewer crescentic glomeruli than rats given the vehicle. These results suggest that T(EM) and some macrophages expressing Kv1.3 channels play a critical role in the pathogenesis of crescentic GN and that Psora-4 will be useful for the treatment of rapidly progressive glomerulonephritis.
Hyodo
Toshitake
T
Dept. of Nephrology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan. dr20015@ndmc.ac.jp
Oda
Takashi
T
Kikuchi
Yuichi
Y
Higashi
Keishi
K
Kushiyama
Taketoshi
T
Yamamoto
Kojiro
K
Yamada
Muneharu
M
Suzuki
Shigenobu
S
Hokari
Ryota
R
Kinoshita
Manabu
M
Seki
Shuhji
S
Fujinaka
Hidehiko
H
Yamamoto
Tadashi
T
Miura
Soichiro
S
Kumagai
Hiroo
H
D000818:Animals; D001323:Autoantibodies; D001485:Basement Membrane / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D005363:Ficusin / Q000627:therapeutic use*; D005921:Glomerulonephritis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D007678:Kidney Glomerulus / Q000276:immunology*; D051664:Kv1.3 Potassium Channel / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D051381:Rats; D011921:Rats, Inbred WKY; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
C499898:5-(4-phenylbutoxy)psoralen; D001323:Autoantibodies; D016207:Cytokines; D051664:Kv1.3 Potassium Channel; C051951:antiglomerular basement membrane antibody; D005363:Ficusin
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