EVALUATION OF COMPONENTS OF THE EXTRACELLULAR PURINERGIC SIGNALING SYSTEM IN HUMAN SEPSIS.
EVALUATION OF COMPONENTS OF THE EXTRACELLULAR PURINERGIC SIGNALING SYSTEM IN HUMAN SEPSIS.
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人类脓毒症细胞外嘌呤能信号系统组件的评估。
DOI：
10.1097/shk.0000000000002230
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发表时间：
2024
期刊：
影响因子：
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通讯作者：
Haskó,György
中科院分区：
文献类型：
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作者：
Lovászi,Marianna;Németh,ZoltánH;Kelestemur,Taha;Sánchez,ItzelV;Antonioli,Luca;Pacher,Pál;Wagener,Gebhard;Haskó,György
细胞外嘌呤如三磷酸腺苷（ATP）、三磷酸尿苷（UTP）和二磷酸尿苷（UDP）以及ATP降解产物腺苷是具有生物活性的信号分子，其在脓毒症的代谢应激部位积累。它们通过结合并激活白细胞表面的P1或腺苷和P2受体而具有强效的免疫调节作用。在这里，我们评估的水平细胞外嘌呤，其受体，代谢酶，和细胞转运蛋白在白细胞中的脓毒症patients.MethodsPeripheral blood mononuclear cells（PBMC），中性粒细胞，血浆中分离出血液中获得的脓毒症患者和健康对照组。从细胞中分离核糖核酸，并测量嘌呤能受体、酶和转运蛋白的mRNA水平。腺苷三磷酸，UTP，UDP，和腺苷水平进行了评价plasma.ResultsAdenosine triphosphate的水平较低，脓毒症患者比健康人，和其他嘌呤水平是两组之间的可比性。P1和P2受体的水平在两个患者组之间没有差异。与健康对照组相比，脓毒症患者外周血单个核细胞中三磷酸二磷酸外核苷水解酶（NTPDase）1或CD39的mRNA水平升高，而NTPDase 2、3和8的mRNA水平降低。脓毒症患者外周血单个核细胞CD73 mRNA表达低于健康人。与健康受试者相比，脓毒症受试者PBMC中平衡核苷转运蛋白（ENT）1 mRNA浓度较高，ENT 2、3和4 mRNA浓度较低。与健康受试者相比，脓毒症受试者PBMC中浓缩核苷转运蛋白（CNT）1 mRNA水平较高，而CNT2、3和4的mRNA水平无差异。我们未能检测到的嘌呤能受体，酶和转运蛋白在中性粒细胞的败血症与健康subjects.ConclusionBecause的mRNA水平的差异CD39降解ATP的腺苷酸（AMP），较低的ATP水平在败血症的个人可能是由于增加CD39的表达。这种ATP降解的增加并没有导致腺苷水平的增加，这可以通过将AMP转化为腺苷的CD73的表达减少来解释。总之，我们的研究结果表明，在人类脓毒症的外周血单个核细胞的嘌呤能系统的组件的差异调节。
ObjectiveExtracellular purines such as adenosine triphosphate (ATP), uridine triphosphate (UTP), and uridine diphosphate (UDP) and the ATP degradation product adenosine are biologically active signaling molecules, which accumulate at sites of metabolic stress in sepsis. They have potent immunomodulatory effects by binding to and activating P1 or adenosine and P2 receptors on the surface of leukocytes. Here we assessed the levels of extracellular purines, their receptors, metabolic enzymes, and cellular transporters in leukocytes of septic patients.MethodsPeripheral blood mononuclear cells (PBMCs), neutrophils, and plasma were isolated from blood obtained from septic patients and healthy control subjects. Ribonucleic acid was isolated from cells, and mRNA levels for purinergic receptors, enzymes, and transporters were measured. Adenosine triphosphate, UTP, UDP, and adenosine levels were evaluated in plasma.ResultsAdenosine triphosphate levels were lower in septic patients than in healthy individuals, and levels of the other purines were comparable between the two groups. Levels of P1 and P2 receptors did not differ between the two patient groups. mRNA levels of ectonucleoside triphosphate diphosphohydrolase (NTPDase) 1 or CD39 increased, whereas those of NTPDase2, 3, and 8 decreased in PBMCs of septic patients when compared with healthy controls. CD73 mRNA was lower in PBMCs of septic than in healthy individuals. Equilibrative nucleoside transporter (ENT) 1 mRNA concentrations were higher and ENT2, 3, and 4 mRNA concentrations were lower in PBMCs of septic subjects when compared with healthy subjects. Concentrative nucleoside transporter (CNT) 1 mRNA levels were higher in PBMCs of septic versus healthy subjects, whereas the mRNA levels of CNT2, 3, and 4 did not differ. We failed to detect differences in mRNA levels of purinergic receptors, enzymes, and transporters in neutrophils of septic versus healthy subjects.ConclusionBecause CD39 degrades ATP to adenosine monophosphate (AMP), the lower ATP levels in septic individuals may be the result of increased CD39 expression. This increased degradation of ATP did not lead to increased adenosine levels, which may be explained by the decreased expression of CD73, which converts AMP to adenosine. Altogether, our results demonstrate differential regulation of components of the purinergic system in PBMCs during human sepsis.