Increased neutrophil adenosine a3 receptor expression is associated with hemorrhagic shock and injury severity in trauma patients.
Increased neutrophil adenosine a3 receptor expression is associated with hemorrhagic shock and injury severity in trauma patients.
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DOI：
10.1097/shk.0b013e318231ee2e
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发表时间：
2011-11
期刊：
影响因子：
--
通讯作者：
Junger WG
中科院分区：
文献类型：
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作者：
Bulger EM;Tower CM;Warner KJ;Garland T;Cuschieri J;Rizoli S;Rhind S;Junger WG
高渗盐水（HS）已被研究作为失血性休克和败血症后的免疫调节剂。中性粒细胞 (PMN) 对 HS 的反应受 ATP 释放的调节，ATP 转化为腺苷并激活腺苷受体。与 A3 腺苷受体结合可促进 PMN 激活，而 A3 受体的抑制可提高 HS 复苏的功效。先前尚未在受伤患者中评估过 PMN A3 受体的表达。全血是在受伤后 2 小时内从 10 名健康志愿者和 60 名受伤患者身上获取的。纳入标准为钝性损伤或穿透性损伤，并有低血容量性休克的证据（SBP≤90mmHg且基础赤字≥6mEq/L或需要输血）；或严重创伤性脑损伤 (TBI) 的证据，包括初始格拉斯哥昏迷评分 (GCS) ≤ 8 或头部 CT 扫描（头部 AIS≥ 3）或现场插管或急诊科的 TBI 证据。通过流式细胞术评估A3受体表达。 PMN 也在体外暴露于 fMLP 或 HS (20-40 mM)。收集的临床数据包括入院生理学、损伤严重程度（ISS 评分）、多器官衰竭的发生情况和生存率。在正常志愿者中，< 1% 的 PMN 在细胞表面表达 A3 受体。受伤患者中 A3 受体表达显着较高，且表达水平与损伤严重程度（ISS ≥ 25：A3 阳性 PMN 36.6% vs. ISS <25：16.2%；p=0.019）和低血容量休克程度（SBP≤90：A3 阳性 PMN 43.8% vs. SBP>90：20.6%；p=0.008）相关。 fMLP 或 HS 刺激会增加正常志愿者中 A3 的表达，但仅限于 ISS < 25 或无低血容量休克的患者。 PMN 表面的 A3 受体表达因损伤而上调，表达水平升高与损伤严重程度和低血容量性休克相关。高渗盐水会增加健康志愿者和较轻损伤患者的 PMN A3 表达。
Hypertonic saline (HS) has been investigated as an immune modulator following hemorrhagic shock and sepsis. The neutrophil (PMN) response to HS is regulated by the release of ATP, which is converted to adenosine and activates adenosine receptors. Binding to A3 adenosine receptors promotes PMN activation and inhibition of A3 receptors improves the efficacy of HS resuscitation. A3 receptor expression of PMN has not been previously evaluated in injured patients. Whole blood was obtained from 10 healthy volunteers and 60 injured patients within 2 hrs of injury. Inclusion criteria were blunt or penetrating injury with evidence of hypovolemic shock (SBP ≤ 90 mmHg and base deficit ≥6 mEq/L or need for blood transfusion); or evidence of severe traumatic brain injury (TBI) including initial Glasgow coma score (GCS) ≤ 8 or evidence of TBI on Head CT scan (Head AIS≥ 3) or intubation in the field or ED. A3 receptor expression was assessed by flow cytometry. PMN were also exposed to fMLP or HS (20-40 mM) in vitro. Clinical data was collected including admission physiology, injury severity (ISS scores), development of multiple organ failure, and survival. In normal volunteers, < 1% of PMN expressed A3 receptors on the cell surface. A3 receptor expression was significantly higher in injured patients and the level of expression correlated with the severity of injury (ISS ≥ 25: A3 positive PMN 36.6% vs. ISS <25: 16.2%; p=0.019) and degree of hypovolemic shock (SBP≤ 90: A3 positive PMN 43.8% vs. SBP>90: 20.6%; p=0.008). Stimulation with fMLP or HS increased A3 expression in normal volunteers, but only in patients with ISS< 25 or without hypovolemic shock. A3 receptor expression on the surface of PMN is up-regulated by injury and increased expression levels are associated with greater injury severity and hypovolemic shock. Hypertonic saline increases A3 expression of PMN from healthy volunteers and less severely injured patients.