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Heparin-coated cardiopulmonary bypass circuits selectively deplete the pattern recognition molecule ficolin-2 of the lectin complement pathway in vivo

机译:肝素包裹的心肺旁路回路选择性地耗尽体内凝集素补体途径的模式识别分子ficolin-2

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摘要

The complement system can be activated via the lectin pathway by the recognition molecules mannose-binding lectin (MBL) and the ficolins. Ficolin-2 exhibits binding against a broad range of ligands, including biomaterials in vitro, and low ficolin-2 levels are associated with increased risk of infections. Thus, we investigated the biocompatibility of the recognition molecules of the lectin pathway in two different types of cardiopulmonary bypass circuits. Bloods were drawn at five time-points before, during and postoperatively from 30 patients undergoing elective cardiac surgery. Patients were randomized into two groups using different coatings of cardiopulmonary bypass circuits, Phisio® (phosphorylcholine polymer coating) and Bioline® (albumin-heparin coating). Concentrations of MBL, ficolin-1, −2 and −3 and soluble C3a and terminal complement complex (TCC) in plasma samples were measured. Ficolin-3-mediated complement activation potential was evaluated with C4, C3 and TCC as output. There was no significant difference between the two circuit materials regarding MBL, ficolin-1 and −3. In the Bioline® group the ficolin-2 levels decreased significantly after initiation of surgery (P < 0·0001) and remained reduced throughout the sampling period. This was not seen for Phisio®-coated circuits. Ficolin-3-mediated complement activation potential was reduced significantly in both groups after start of operation (P < 0·0001), whereas soluble C3a and TCC in the samples were increased (P < 0·0001). Ficolin-2 was depleted from plasma during cardiac surgery when using heparin-coated bypass circuits and did not reach baseline level 24 h postoperation. These findings may have implications for the postoperative susceptibility to infections in patients undergoing extracorporeal circulation procedures.
机译:补体系统可以通过凝集素途径被识别分子甘露糖结合凝集素(MBL)和纤维蛋白素激活。 Ficolin-2表现出对广泛范围的配体(包括体外生物材料)的结合,而Ficolin-2的水平低与感染风险增加相关。因此,我们研究了两种不同类型的体外循环回路中凝集素途径识别分子的生物相容性。在30例接受择期心脏手术的患者的术前,术中和术后五个时间点抽血。使用不同的心肺旁路回路涂层将患者分为两组,分别为Phisio®(磷酸胆碱聚合物涂层)和Bioline®(白蛋白-肝素涂层)。测量血浆样品中MBL,ficolin-1,-2和-3以及可溶性C3a和末端补体复合物(TCC)的浓度。用C4,C3和TCC作为输出评估Ficolin-3介导的补体激活潜能。两种电路材料在MBL,ficolin-1和-3之间没有显着差异。在Bioline®组中,手术开始后Ficolin-2的水平显着下降(P <0·0001),并在整个采样期间保持下降。对于Phisio®涂层电路,这是看不到的。手术开始后两组中Ficolin-3介导的补体激活潜能均显着降低(P <0·0001),而样品中的可溶性C3a和TCC升高(P <0·0001)。当使用肝素涂层旁路回路进行心脏手术时,Ficolin-2的血浆消耗de尽,术后24h未达到基线水平。这些发现可能对接受体外循环程序的患者术后易感性有影响。

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