Department of Biomedicine, Physiology, Aarhus University, Ole Worms Alle 3, build 1170, 8000, Aarhus C, Denmark.
Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Crit Care. 2018 Aug 2;22(1):181. doi: 10.1186/s13054-018-2100-3.
Pore-forming proteins released from bacteria or formed as result of complement activation are known to produce severe cell damage. Inhibition of purinergic P2X receptors markedly reduces damage inflicted by cytolytic bacterial toxin and after complement activation in both erythrocytes and monocytes. P2X expression generally shows variation throughout the population. Here, we investigate correlation between P2X receptor abundance in blood cell plasma membranes and haematocrit during sepsis, in patients admitted to the emergency department (ED) or intensive care unit (ICU).
Patients admitted to the ED and successively transferred to ICU with the diagnosis sepsis (< 2 systemic inflammatory response syndrome (SIRS) criteria and suspected infection), were grouped as either blood pathogen-positive (14 patients) or blood pathogen-negative (20 patients). Blood samples drawn at ICU admission were analysed for P2X and P2X receptor abundance using indirect flow cytometry.
Here, we find inverse correlation between P2X receptor expression and change in haematocrit (r - 0.80) and haemoglobin (r - 0.78) levels from admission to ED to arrival at ICU in patients with pathogen-positive sepsis. This correlation was not found in patients without confirmed bacteraemia. Patients with high P2X expression had a significantly greater change in both haematocrit (- 0.59 ± 0.36) and haemoglobin levels (- 0.182 ± 0.038 mg/dl) per hour, during the first hours after hospital admission compared to patients with low P2X expression (0.007 ± 0.182 and - 0.020 ± 0.058 mg/dl, respectively).
High levels of P2X are correlated with more pronounced reduction in haematocrit and haemoglobin in patients with confirmed bacteraemia. This supports previous in vitro findings of P2X activation as a significant component in cell damage caused by pore-forming bacterial toxins and complement-dependent major attack complex. These data suggest a new potential target for future therapeutics in initial stages of sepsis.
已知从细菌释放或作为补体激活结果形成的孔形成蛋白会导致严重的细胞损伤。嘌呤能 P2X 受体的抑制可显著减少细胞溶菌细菌毒素和补体激活后在红细胞和单核细胞中造成的损伤。P2X 的表达在人群中普遍存在差异。在这里，我们研究了脓毒症期间血细胞质膜中 P2X 受体丰度与血细胞比容之间的相关性，在急诊室 (ED) 或重症监护病房 (ICU) 入院的患者中。
将诊断为脓毒症的 ED 入院并随后转入 ICU 的患者（<2 个全身炎症反应综合征 (SIRS) 标准和疑似感染）分为血病原体阳性（14 例）或血病原体阴性（20 例）。在 ICU 入院时采集的血液样本使用间接流式细胞术分析 P2X 和 P2X 受体丰度。
在这里，我们发现与血病原体阳性脓毒症患者从 ED 入院到 ICU 到达时的血细胞比容（r=-0.80）和血红蛋白（r=-0.78）水平变化呈负相关。在没有确认菌血症的患者中未发现这种相关性。高 P2X 表达的患者在入院后最初几小时内，血细胞比容（-0.59±0.36）和血红蛋白水平（-0.182±0.038 mg/dl）的变化明显更大，而低 P2X 表达的患者（分别为 0.007±0.182 和-0.020±0.058 mg/dl）。
在确认菌血症的患者中，高水平的 P2X 与血细胞比容和血红蛋白更明显的降低相关。这支持了先前关于 P2X 激活作为孔形成细菌毒素和补体依赖性主要攻击复合物引起的细胞损伤的重要组成部分的体外发现。这些数据表明，在脓毒症的早期阶段，新的潜在治疗靶点。
