A protein toxin from the sea anemone Phyllodiscus semoni targets the kidney and causes a severe renal injury with predominant glomerular endothelial damage
A protein toxin from the sea anemone Phyllodiscus semoni targets the kidney and causes a severe renal injury with predominant glomerular endothelial damage
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DOI：
10.2353/ajpath.2007.060984
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发表时间：
2007-08-01
影响因子：
6
通讯作者：
Matsuo, Seiichi
中科院分区：
文献类型：
--
作者：
Mizuno, Masashi;Nozaki, Masatoshi;Matsuo, Seiichi
海葵Phyllodiscus semoni的毒液会导致人类爆发性皮炎，很少会导致急性肾衰竭。在这里，我们调查是否从包囊提取的毒液（PsTX-T）是肾毒性时，静脉注射给药的大鼠和PsTX-T是否诱导补体系统的激活。虽然小剂量PsTX-T在大鼠中诱导了与患者中所见病理相似的急性肾小管坏死，但在每只动物给予0.03 mg PsTX-T后24小时，肾脏显示肾小球损伤，伴有肾小球内皮损伤、血栓形成、系膜溶解和肾小球基底膜部分破裂，并伴有严重的肾小管坏死，类似于严重溶血性尿毒症综合征的典型肾小球表现。早期损伤伴随着特异性PsTX-T结合、大量补体C3 b和膜攻击复合物在损伤区域的肾小球中沉积以及肾小球补体调节因子表达的降低。通过证明全身性补体抑制减少肾损伤，证实了补体的致病作用。分离的肾毒性成分，115 kd的蛋白毒素（PsTX-115），被证明会导致相同的肾脏病理。PsTX-T和PsTX-115通过诱导补体激活具有高度肾毒性作用的证明表明，抑制补体可用于预防由P. semoni毒液蛰入后的急性肾损伤。
Envenomation by the sea anemone Phyllodiscus semoni causes fulminant dermatitis and, rarely, acute renal failure in humans. Here, we investigated whether the venom extracted from the nematocysts (PsTX-T) was nephrotoxic when administered intravenously in rats and whether PsTX-T induced activation of the complement system. Although small dose of PsTX-T induced acute tubular necrosis in rats resembling pathology seen in patients, kidneys displayed glomerular injury with glomerular endothelial damage, thrombus formation, mesangiolysis, and partial rupture of glomerular basement membrane, accompanied by severe tubular necrosis at 24 hours after administration of 0.03 mg of PsTX-T per animal, similar to the glomerular findings typical of severe hemolytic uremic syndrome. The early stage injury was accompanied by specific PsTX-T binding, massive complement C3b, and membrane attack complex deposition in glomeruli in the regions of injury and decreased glomerular expression of complement regulators. A pathogenic role for complement was confirmed by demonstrating that systemic complement inhibition reduced renal injury. The isolated nephrotoxic component, a 115-kd protein toxin (PsTX-115), was shown to cause identical renal pathology. The demonstration that PsTX-T and PsTX-115 were highly nephrotoxic acting via induction of complement activation suggests that inhibition of complement might be used to prevent acute renal damage following envenomation by P.semoni.