Center for Experimental Medical Research (CeRMS), University of Torino, Via Santena 5, Torino 10126, Italy.
Crit Care. 2010;14(1):R4. doi: 10.1186/cc8835. Epub 2010 Jan 11.
A pro-apoptotic effect of circulating mediators on renal tubular epithelial cells has been involved in the pathogenesis of sepsis-associated acute kidney injury (AKI). Adsorption techniques have been showed to efficiently remove inflammatory cytokines from plasma. The aim of this study was to evaluate the efficiency of the hydrophobic resin Amberchrom CG161 M to adsorb from septic plasma soluble mediators involved in tubular injury.
We enrolled in the study 10 critically ill patients with sepsis-associated AKI and we evaluated the effects of their plasma on granulocyte adhesion, apoptosis and functional alterations of cultured human kidney tubular epithelial cells. We established an in vitro model of plasma adsorption and we studied the protective effect of unselective removal of soluble mediators by the Amberchrom CG161 M resin on septic plasma-induced tubular cell injury.
Plasma from septic patients induced granulocyte adhesion, apoptosis and altered polarity in tubular cells. Plasma adsorption significantly decreased these effects and abated the concentrations of several soluble mediators. The inhibition of granulocyte adhesion to tubular cells was associated with the down-regulation of ICAM-1 and CD40. Resin adsorption inhibited tubular cell apoptosis induced by septic plasma by down-regulating the activation of caspase-3, 8, 9 and of Fas/death receptor-mediated signalling pathways. The alteration of cell polarity, morphogenesis, protein reabsorption and the down-regulation of the tight junction molecule ZO-1, of the sodium transporter NHE3, of the glucose transporter GLUT-2 and of the endocytic receptor megalin all induced by septic plasma were significantly reduced by resin adsorption.
Septic plasma induced a direct injury of tubular cells by favouring granulocyte adhesion, by inducing cell apoptosis and by altering cell polarity and function. All these biological effects are related to the presence of circulating inflammatory mediators that can be efficiently removed by resin adsorption with a consequent limitation of tubular cell injury.
循环介质对肾小管上皮细胞的促凋亡作用与脓毒症相关急性肾损伤（AKI）的发病机制有关。吸附技术已被证明可有效地从血浆中去除炎症细胞因子。本研究旨在评估疏水性树脂 Amberchrom CG161 M 从脓毒症血浆中吸附参与肾小管损伤的可溶性介质的效率。
我们纳入了 10 名患有脓毒症相关 AKI 的危重病患者，并评估了他们的血浆对粒细胞黏附、凋亡和培养的人肾小管上皮细胞功能改变的影响。我们建立了血浆吸附的体外模型，并研究了 Amberchrom CG161 M 树脂对脓毒症血浆诱导的肾小管细胞损伤的非选择性去除可溶性介质的保护作用。
脓毒症患者的血浆诱导粒细胞黏附、凋亡和改变肾小管细胞极性。血浆吸附显著降低了这些作用，并降低了几种可溶性介质的浓度。粒细胞黏附至肾小管细胞的抑制与 ICAM-1 和 CD40 的下调有关。树脂吸附通过下调半胱天冬酶-3、8、9 和 Fas/死亡受体介导的信号通路的激活，抑制由脓毒症血浆诱导的肾小管细胞凋亡。树脂吸附还显著减少了细胞极性、形态发生、蛋白质重吸收以及紧密连接分子 ZO-1、钠转运体 NHE3、葡萄糖转运体 GLUT-2 和内吞受体 megalin 的下调，这些改变均由脓毒症血浆诱导。
脓毒症血浆通过促进粒细胞黏附、诱导细胞凋亡和改变细胞极性和功能，直接损伤肾小管细胞。所有这些生物学效应都与循环炎症介质的存在有关，这些介质可通过树脂吸附有效地去除，从而限制肾小管细胞损伤。
