首页> 外文期刊>American Journal of Physiology >Free circulating active elastase contributes to chronic inflammation in patients on hemodialysis
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Free circulating active elastase contributes to chronic inflammation in patients on hemodialysis

机译:自由循环活性弹性酶在血液透析患者中有助于慢性炎症

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Atherosclerosis and cardiovascular complications are prevalent among patients undergoing chronic hemodialysis (HD). In this population, peripheral polymor-phonuclear leukocytes (PMNLs) are primed, releasing proinflamma-tory mediators such as elastase. Elastase is normally inhibited by a specific inhibitor, avoiding undesirable degradation of cellular and extracellular components. This study tested the hypothesis that in states of noninfectious inflammation, elastase is released by PMNLs and acts in an uncontrolled manner to inflict vascular damage. Blood was collected from patients undergoing HD and healthy controls (HC). PMNL intracellular and surface expressions of elastase were determined by quantitative real-time PCR, Western blotting, and flow cytometry. The elastase activity was evaluated using a fluorescent substrate. The levels of serum α1-anlitrypsin (α1-AT), the natural elastase inhibitor, were determined by Western blot. Free active elastase was elevated in HD sera, whereas the levels of α1-AT were decreased compared with HC. The levels of the intracellular elastase enzyme and its activity were lower in HD PMNLs despite similar expression levels of elastase mRNA. Elastase binding to PMNL cell surface was higher in HD compared with HC. The increased circulating levels of free active elastase released from primed HD PMNLs together with the higher cell surface-bound enzymes and the lower levels of α1-AT result in the higher elastase activity in HD sera. This exacerbated elastase activity could lead to the endothelial dysfunction, as hypothesized. In addition, it suggests that free circulating elastase can serve as a new biomarker and therapeutic target to reduce inflammation and vascular complications in patients on hemodialysis.
机译:在接受慢性血液透析(HD)的患者中,动脉粥样硬化和心血管并发症是普遍的。在该群体中,外周聚合物 - 晶术白细胞(PMNL)被灌注,释放促胰酶等植物介质。 elastase通常被特异性抑制剂抑制,避免了细胞和细胞外组分的不希望的降解。本研究测试了假设,即在非缺陷炎症状态下,弹性蛋酶通过PMNLS释放并以不受控制的方式作用,以造成血管损伤。从接受HD和健康对照(HC)的患者中收集血液。通过定量实时PCR,Western印迹和流式细胞术测定弹性蛋白酶的PMNL细胞外和表面表达。使用荧光基底评价弹性蛋白酶活性。通过Western印迹测定血清α1-脂素(α1-AT),天然弹性蛋白酶抑制剂的水平。自由活性弹性酶在高清血清中升高,而与HC相比,α1-α的水平降低。尽管弹性蛋白酶mRNA的表达水平相似,但细胞内弹性蛋白酶和其活性的水平较低。与HC相比,HD的弹性蛋白酶与PMN1细胞表面的结合较高。从灌注的HD PMN1释放的游离活性弹性蛋白酶的循环水平增加以及较高的细胞表面结合酶和较低水平的α1-得到的HD血清中的较高弹性蛋白酶活性。这种加剧的弹性蛋白酶活性可能导致内皮功能障碍,如假设。此外,它表明自由循环弹性蛋白酶可以作为新的生物标志物和治疗靶标,以减少血液透析患者患者的炎症和血管并发症。

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