Anti-perforin antibody treatment ameliorates experimental crescentic glomerulonephritis in WKY rats.

Anti-perforin antibody treatment ameliorates experimental crescentic glomerulonephritis in WKY rats. Research Abstract Details 

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Anti-perforin antibody treatment ameliorates experimental crescentic glomerulonephritis in WKY rats. Abstract Text:

H Fujinaka,T Yamamoto,L Feng,M Nameta,G Garcia,S Chen,Ag A El-shemi,K Ohshiro,K Katsuyama,Y Yoshida,E Yaoita,C B Wilson,H Fujinaka,T Yamamoto,L Feng,M Nameta,G Garcia,S Chen,Ag A El-shemi,K Ohshiro,K Katsuyama,Y Yoshida,E Yaoita,C B Wilson,

The depletion of CD8+ cells has been shown to prevent the initiation and progression of antiglomerular basement membrane (GBM) crescentic glomerulonephritis (GN) in Wistar-Kyoto (WKY) rats. In this study, we asked whether CD8+ cells produce their effects by perforin/granzyme-mediated or by Fas ligand (FasL)-mediated pathways. The glomerular mRNA expression of perforin and granzyme B corresponded with the number of CD8+ cells, whereas that of granzyme A, Fas, and FasL did not. The enhanced mRNA level of perforin and granzyme B was not evident in CD8+-depleted rats. The number of apoptotic cells in the glomeruli was significantly increased at day 3. Perforin mRNA was found in cells infiltrating the glomerulus by in situ hybridization and by using dual-staining immunohistochemistry perforin protein was found in glomerular CD8+ cells. We found that perforin was readily visualized at the inner surface of the glomerular capillaries by immunoelectron microscopy. Based on these results, we treated animals with a perforin antibody in vivo and found that it significantly reduced the amount of proteinuria, frequency of crescentic glomeruli, and the number of glomerular monocytes and macrophages, although the number of glomerular CD8+ cells was not changed. Our results suggest that CD8+ cells play a role in glomerular injury as effector cells in part through a perforin/granzyme-mediated pathway in the anti-GBM WKY rat model of crescentic GN.

Anti-perforin antibody treatment ameliorates experimental crescentic glomerulonephritis in WKY rats. Publishing Authors By Initials

H Fujinaka,T Yamamoto,L Feng,M Nameta,G Garcia,S Chen,AA El-shemi,K Ohshiro,K Katsuyama,Y Yoshida,E Yaoita,CB Wilson,H Fujinaka,T Yamamoto,L Feng,M Nameta,G Garcia,S Chen,AA El-shemi,K Ohshiro,K Katsuyama,Y Yoshida,E Yaoita,CB Wilson,

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Anti-perforin antibody treatment ameliorates experimental crescentic glomerulonephritis in WKY rats. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Kidney international

VOLUME: 72

Page Numbers: 823-30

Journal Abbreviation: Kidney Int.

ISSN: 0085-2538

DAY: 11

MONTH: 07

YEAR: 2007

Anti-perforin antibody treatment ameliorates experimental crescentic glomerulonephritis in WKY rats. Information

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LANGUAGE: eng

NlmUniqueID: 323470

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Grant and Affiliation Information for Anti-perforin antibody treatment ameliorates experimental crescentic glomerulonephritis in WKY rats.

AFFILIATION: Department of Structural Pathology, Institute of Nephrology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan. dext007@hotmail.com

Country: United States

AGENCY: United States NIDDK

GRANT: DK 20043

ACRONYM: DK

MEDLINETA: Kidney Int

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