scholarly journals Increased oxygen radical and eicosanoid formation in immune-mediated mesangial cell injury

1992 ◽  
Vol 42 (1) ◽  
pp. 69-74 ◽  
Author(s):  
Gerhard P. Oberle ◽  
Jan. Niemeyer ◽  
Friedrich Thaiss ◽  
Wilhelm Schoeppe ◽  
Rolf A.K. Stahl
1990 ◽  
Vol 38 (2) ◽  
pp. 273-281 ◽  
Author(s):  
Rolf A.K. Stahl ◽  
Friedrich Thaiss ◽  
Sabine Kahf ◽  
Wilhelm Schoeppe ◽  
Udo M. Helmchen

2007 ◽  
Vol 292 (6) ◽  
pp. F1761-F1770 ◽  
Author(s):  
Sebastian Martini ◽  
Stephanie Krämer ◽  
Tanja Loof ◽  
Yingrui Wang-Rosenke ◽  
Ute Daig ◽  
...  

FTY720 is a novel immune modulator whose primary action is blood lymphocyte depletion through interaction with sphingosine-1-phosphate (S1P) receptors. The present study analyzes the effect of FTY720 on both the early mesangial cell injury and the subsequent matrix expansion phase of experimental mesangioproliferative glomerulonephritis. Disease was induced by injection of OX-7 anti-thy1 antibody into male Wistar rats. In both protocols, FTY720 administration (0.3 mg/kg body wt) resulted in a selective and very marked reduction in blood lymphocyte count. In the injury experiment, the S1P receptor modulator was given starting 5 days before and continued until 1 day after antibody injection. FTY720 did not significantly affect the degree of anti-thy1-induced mesangial cell lysis and glomerular-inducible nitric oxide production. In the matrix expansion experiment, FTY720 treatment was started 1 day after antibody injection and continued until day 7. In this protocol, the S1P modulator reduced proteinuria, histological matrix expansion, and glomerular protein expression of TGF-β1, fibronectin, and PAI-1. Glomerular collagen III staining intensity was decreased. FTY720 reduced markedly glomerular lymphocyte number per cross section and to a lesser degree macrophage infiltration. In conclusion, FTY720 significantly limits TGF-β1 overexpression and matrix protein expression following induction of acute anti-thy glomerulonephritis, involving reductions in blood and glomerular lymphocyte numbers. The results suggest that lymphocytes actively contribute to matrix expansion in experimental mesangioproliferative glomerulonephritis. Our study expands on findings on FTY720's beneficial effects on tubulointerstitial and functional disease progression previously reported in anti-thy1-induced chronic glomerulosclerosis.


Author(s):  
Boyang Xu ◽  
Li Zhu ◽  
Qingsong Wang ◽  
Yanfeng Zhao ◽  
Meng Jia ◽  
...  

Abstract Background IgA nephropathy (IgAN) is characterized by predominant IgA deposition in the glomerular mesangium. Previous studies proved that renal-deposited IgA in IgAN came from circulating IgA1-containing complexes (CICs). Methods To explore the composition of CICs in IgAN, we isolated CICs from IgAN patients and healthy controls, and then quantitatively analyzed them by mass spectrometry. Meanwhile, the isolated CICs were used to treat human mesangial cells to monitor mesangial cell injury. Taken together the proteins content and injury effects, the key constituent in CICs was identified. Then, the circulating levels of identified key constituent-IgA complex were detected in an independent population by an in-house-developed ELISA. Results By comparing the proteins of CICs between IgAN patients and controls, we found that 14 proteins showed significantly different levels. Among them, alpha-1-microglobulin content in CICs was associated with not only in vitro mesangial cell proliferation and MCP-1 secretion but also in vivo eGFR levels and tubulointerstitial lesions in IgAN patients. Moreover, we found alpha-1-microglobulin was prone to bind aberrant glycosylated IgA1. Additionally, an elevated circulating IgA-alpha-1-microglobulin complex levels were detected in an independent IgAN population, and IgA-alpha-1-microglobulin complex levels were correlated with hypertension, eGFR levels and Oxford-T scores in these IgAN patients. Conclusions Our results suggest that the IgA-alpha-1-microglobulin complex is an important constituent in CICs, and that circulating IgA-alpha-1-microglobulin complex detection might serve as a potential noninvasive biomarker detection method for IgAN.


2020 ◽  
Vol 382 (3) ◽  
pp. 627-638 ◽  
Author(s):  
Li-Hua Zhang ◽  
Bin Xiao ◽  
Miao Zhong ◽  
Qiao Li ◽  
Jian-Ying Chen ◽  
...  

Blood ◽  
2006 ◽  
Vol 107 (3) ◽  
pp. 1184-1191 ◽  
Author(s):  
Nobuyoshi Hanaoka ◽  
Tatsuya Kawaguchi ◽  
Kentaro Horikawa ◽  
Shoichi Nagakura ◽  
Hiroaki Mitsuya ◽  
...  

AbstractThe mechanism by which paroxysmal nocturnal hemoglobinuria (PNH) clones expand is unknown. PNH clones harbor PIGA mutations and do not synthesize glycosylphosphatidylinositol (GPI), resulting in deficiency of GPI-linked membrane proteins. GPI-deficient blood cells often expand in patients with aplastic anemia who sustain immune-mediated marrow injury putatively induced by cytotoxic cells, hence suggesting that the injury allows PNH clones to expand selectively. We previously reported that leukemic K562 cells preferentially survived natural killer (NK) cell-mediated cytotoxicity in vitro when they acquired PIGA mutations. We herein show that the survival is ascribable to the deficiency of stress-inducible GPI-linked membrane proteins ULBP1 and ULBP2, which activate NK and T cells. The ULBPs were detected on GPI-expressing but not on GPI-deficient K562 cells. In the presence of antibodies to either the ULBPs or their receptor NKG2D on NK cells, GPI-expressing cells were as less NK sensitive as GPI-deficient cells. NK cells therefore spared ULBP-deficient cells in vitro. The ULBPs were identified only on GPI-expressing blood cells of a proportion of patients with PNH but none of healthy individuals. Granulocytes of the patients partly underwent killing by autologous cytotoxic cells, implying ULBP-associated blood cell injury. In this setting, the lack of ULBPs may allow immunoselection of PNH clones.


Renal Failure ◽  
2018 ◽  
Vol 40 (1) ◽  
pp. 364-370 ◽  
Author(s):  
Lu Gan ◽  
Xiaozhao Li ◽  
Mengyuan Zhu ◽  
Chen Chen ◽  
Huimin Luo ◽  
...  

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Lina Wu ◽  
Qingzhu Wang ◽  
Feng Guo ◽  
Xiaojun Ma ◽  
Hongfei Ji ◽  
...  

Nephron ◽  
1996 ◽  
Vol 74 (1) ◽  
pp. 197-203 ◽  
Author(s):  
Pravin C. Singhal ◽  
Calvin Q. Pan ◽  
Sushil Sagar ◽  
E. Valderrama ◽  
Rolf A.K. Stahl

PLoS ONE ◽  
2015 ◽  
Vol 10 (2) ◽  
pp. e0117400 ◽  
Author(s):  
Xinxing Lu ◽  
Qiuling Fan ◽  
Li Xu ◽  
Lin Li ◽  
Yuan Yue ◽  
...  

1992 ◽  
Vol 42 (2) ◽  
pp. 480-487 ◽  
Author(s):  
Hugh R. Brady ◽  
Mark D. Denton ◽  
Wladimiro Jimenez ◽  
Shoichiro Takata ◽  
Deborah Palliser ◽  
...  

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