Glomerular fibrinolytic activity in anti-GBM glomerulonephritis in rabbits.
Glomerular fibrinolytic activity in anti-GBM glomerulonephritis in rabbits.
复制标题
兔抗 GBM 肾小球肾炎中的肾小球纤溶活性。
作者：
Jim Malliaros;Jim Malliaros;S. Holdsworth;S. Holdsworth;Johann Wojta;Johann Wojta;Jonathan H. Erlich;Jonathan H. Erlich;P. Tipping;P. Tipping
纤维蛋白酶是严重增生性肾小球肾炎（GN）损伤的重要介质。正常肾小球表达纤维蛋白溶解活性，其可保护免于纤维蛋白沉积的损伤作用。肾小球纤维蛋白溶解活性（GFA）的变化可能在调节GN中纤维蛋白积聚中起重要作用。为了研究肾小球肾炎中与纤维蛋白沉积相关的GFA的变化，在兔中研究了自体相抗肾小球基底膜抗体（抗GBM GN）。与肾小球纤维蛋白沉积相关的净GFA显著降低（1.3 ± 0.8 ng纤维蛋白溶解/10（3）个肾小球/2小时，正常57.1 ± 25.4 ng纤维蛋白溶解/10（3）个肾小球/2小时，P < 0.02）。纤维蛋白相关性肾炎中GFA减少与组织型纤溶酶原激活物（tPA）表达减少、纤溶酶原激活物抑制物-1（派-1）表达增加和肾小球巨噬细胞浸润相关。在抗GBM诱导的GN（异源期）的纤维蛋白非依赖性模型中，在同等损伤（蛋白尿）下，净GFA增加（174 +/- 64 ng纤维蛋白溶解/10（3）肾小球/2小时）。这与tPA和uPA增加以及在没有显著的巨噬细胞浸润的情况下派-1降低有关。这些研究表明，GN中的纤维蛋白沉积与GFA的净减少相关，这归因于纤溶酶原激活物表达的减少和派-1的增加。GFA的减少可能会加重肾小球纤维蛋白沉积和随后的肾小球损伤。肾小球巨噬细胞流入和GFA减少之间的关联表明，这种变化可能是由巨噬细胞指导的。
Fibrin is an important mediator of injury in severe proliferative forms of glomerulonephritis (GN). Normal glomeruli express fibrinolytic activity, which may protect against the injurious effects of fibrin deposition. Changes in glomerular fibrinolytic activity (GFA) may play an important role in modulating fibrin accumulation in GN. To study the changes in GFA associated with fibrin deposition in GN, autologous phase anti-glomerular basement antibody initiated GN (anti-GBM GN) was studied in rabbits. Net GFA was significantly reduced in association with glomerular fibrin deposition (1.3 +/- 0.8 ng fibrin lysed/10(3) glomeruli/2 hr, normal 57.1 +/- 25.4 ng fibrin lysed/10(3) glomeruli/2 hr, P < 0.02). Reduced GFA in fibrin associated GN was associated with decreased expression of tissue type plasminogen activator (tPA) and increased expression of plasminogen activator inhibitor type-1 (PAI-1) and glomerular macrophage infiltration. In a fibrin independent model of anti-GBM induced GN (heterologous phase), with equivalent injury (proteinuria), net GFA was increased (174 +/- 64 ng fibrin lysed/10(3) glomeruli/2 hr). This was associated with increased tPA and uPA, and decreased PAI-1 in the absence of significant macrophage infiltration. These studies demonstrate that fibrin deposition in GN is associated with a net reduction of GFA, attributable to reduced expression of plasminogen activators and augmentation of PAI-1. Reduction of GFA may potentiate glomerular fibrin deposition and consequent glomerular injury. The association between glomerular macrophage influx and reduction in GFA suggests that this change may be directed by macrophages.
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反向纤维蛋白自显影：十二烷基硫酸钠-聚丙烯酰胺凝胶电泳后检测和部分表征蛋白酶抑制剂的方法。
影响因子：
2.9
作者：
Erickson,LA;Lawrence,DA;Loskutoff,DJ
通讯作者：
Loskutoff,DJ
影响因子：
15.9
作者：
HOLDSWORTH, SR;NEALE, TJ;WILSON, CB
通讯作者：
WILSON, CB
内皮细胞产生纤溶酶原激活剂的潜在抑制剂，可以被变性剂激活。
DOI：
--
发表时间：
1985
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Hekman,CM;Loskutoff,DJ
通讯作者：
Loskutoff,DJ
DOI：
--
发表时间：
1988-12
期刊：
The American journal of pathology
影响因子：
--
作者：
J. Pober
通讯作者：
J. Pober
DOI：
10.1161/01.atv.6.6.601
发表时间：
1986-11-01
期刊：
ARTERIOSCLEROSIS
影响因子：
--
作者：
TSUKADA, T;ROSENFELD, M;GOWN, AM
通讯作者：
GOWN, AM