학술논문

Voltage-gated potassium channel Kvl.3 blocker as a potential treatment for rat anti-glomerular basement membrane glomerulonephritis
Document Type
Author abstract
Report
Source
American Journal of Physiology (Consolidated). Dec 2010, Vol. 299 Issue 6, pF1258, 12 p.
Subject
Health aspects
Research
Risk factors
Care and treatment
Physiological aspects
Genetic aspects
T cells -- Health aspects
T cells -- Research
Glomerulonephritis -- Risk factors
Glomerulonephritis -- Care and treatment
Glomerulonephritis -- Research
Potassium channels -- Physiological aspects
Potassium channels -- Genetic aspects
Potassium channels -- Research
Language
English
ISSN
0002-9513
Abstract
The voltage-gated potassium channel Kvl.3 has been recently identified as a molecular target that allows the selective pharmacological suppression of effector memory T cells ([T.sub.EM]) without affecting the function of naive T cells (TN) and central memory T cells ([T.sub.CM]). We found that Kvl.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.sup.+] T cells and some of the [CD8.sup.+] T cells had the [T.sub.EM] phenotype ([CD45RC.sup.-][CD62L.sup.-]). Double immunofluorescence staining using mononuclear cell suspensions isolated from anti-GBM GN kidney showed that Kvl.3 was expressed on T cells and some macrophages. We therefore investigated whether the Kvl.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.sub.EM] and some macrophages expressing Kvl.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. WKY rats; crescentic glomerulonephritis; flow cytometric analysis doi: 10.1152/ajprenal.00374.2010

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