Osthoff Michael, Trendelenburg Marten
Department of Infectious Diseases, University Hospital Basel, Petersgraben 4, 4031 Basel, Switzerland.
Laboratory of Clinical Immunology, Department of Biomedicine, University Hospital Basel, Petersgraben 4, 4031 Basel, Switzerland ; Clinic for Internal Medicine, University Hospital Basel, Petersgraben 4, 4031 Basel, Switzerland.
Biomed Res Int. 2013;2013:962695. doi: 10.1155/2013/962695. Epub 2013 Dec 10.
Contrast-induced nephropathy (CIN) is the third leading cause of acute renal failure in hospitalized patients. Endothelial dysfunction, renal medullary ischemia, and tubular toxicity are regarded as the most important factors in the pathogenesis of CIN. Mannose-binding lectin (MBL), a pattern recognition protein of the lectin pathway of complement, has been found to aggravate and mediate tissue damage during experimental renal ischemia/reperfusion (I/R) injury which was alleviated by inhibition with C1 inhibitor, a potent MBL, and lectin pathway inhibitor. In this paper, we highlight the potential role of MBL in the pathogenesis of human CIN. In experimental I/R models, MBL was previously found to induce tubular cell death independent of the complement system. In addition, after binding to vascular endothelial cells, MBL and its associated serine proteases were able to trigger a proinflammatory reaction and contribute to endothelial dysfunction. In humans, urinary MBL was increased after administration of contrast media and in individuals with CIN. Moreover, individuals with normal/high MBL levels were at increased risk to develop radiocontrast-induced renal dysfunction. Hence, MBL and the lectin pathway seem to be a promising target given that a licensed, powerful, human recombinant inhibitor exits to be added to the scarce armamentarium currently available for prophylaxis of CIN.
造影剂肾病（CIN）是住院患者急性肾衰竭的第三大主要病因。内皮功能障碍、肾髓质缺血和肾小管毒性被认为是CIN发病机制中最重要的因素。甘露糖结合凝集素（MBL）是补体凝集素途径的一种模式识别蛋白，已发现在实验性肾缺血/再灌注（I/R）损伤期间，它会加重并介导组织损伤，而用C1抑制剂（一种有效的MBL和凝集素途径抑制剂）抑制可减轻这种损伤。在本文中，我们强调了MBL在人类CIN发病机制中的潜在作用。在实验性I/R模型中，先前发现MBL可独立于补体系统诱导肾小管细胞死亡。此外，MBL与其相关的丝氨酸蛋白酶结合后，能够引发促炎反应并导致内皮功能障碍。在人类中，使用造影剂后以及CIN患者的尿液中MBL会升高。此外，MBL水平正常/较高的个体发生放射性造影剂诱导的肾功能障碍的风险增加。因此，鉴于有一种已获许可的、强大的人重组抑制剂，MBL和凝集素途径似乎是一个有前景的靶点，可被添加到目前用于预防CIN的稀缺手段中。
