Department of Neurological Surgery, University of Miami, Miami, FL 33136, USA.
Diabetes Research Institute, University of Miami; Miami, FL 33136, USA.
Cells. 2019 Jan 18;8(1):69. doi: 10.3390/cells8010069.
Approximately 30% of traumatic brain injured patients suffer from acute lung injury or acute respiratory distress syndrome. Our previous work revealed that extracellular vesicle (EV)-mediated inflammasome signaling plays a crucial role in the pathophysiology of traumatic brain injury (TBI)-induced lung injury. Here, serum-derived EVs from severe TBI patients were analyzed for particle size, concentration, origin, and levels of the inflammasome component, an apoptosis-associated speck-like protein containing a caspase-recruiting domain (ASC). Serum ASC levels were analyzed from EV obtained from patients that presented lung injury after TBI and compared them to EV obtained from patients that did not show any signs of lung injury. EVs were co-cultured with lung human microvascular endothelial cells (HMVEC-L) to evaluate inflammasome activation and endothelial cell pyroptosis. TBI patients had a significant increase in the number of serum-derived EVs and levels of ASC. Severe TBI patients with lung injury had a significantly higher level of ASC in serum and serum-derived EVs compared to individuals without lung injury. Only EVs isolated from head trauma patients with gunshot wounds were of neural origin. Delivery of serum-derived EVs to HMVEC-L activated the inflammasome and resulted in endothelial cell pyroptosis. Thus, serum-derived EVs and inflammasome proteins play a critical role in the pathogenesis of TBI-induced lung injury, supporting activation of an EV-mediated neural-respiratory inflammasome axis in TBI-induced lung injury.
约 30%的创伤性脑损伤患者患有急性肺损伤或急性呼吸窘迫综合征。我们之前的工作表明，细胞外囊泡（EV）介导的炎症小体信号在创伤性脑损伤（TBI）引起的肺损伤的病理生理学中起着关键作用。在这里，分析了来自严重 TBI 患者的血清源性 EV 的粒径、浓度、来源以及炎症小体成分（一种包含半胱天冬酶募集结构域的凋亡相关斑点样蛋白）的水平。分析了 TBI 后出现肺损伤的患者从 EV 中获得的血清 ASC 水平，并将其与未显示任何肺损伤迹象的患者从 EV 中获得的血清 ASC 水平进行比较。将 EV 与人肺微血管内皮细胞（HMVEC-L）共培养，以评估炎症小体的激活和内皮细胞焦亡。TBI 患者的血清源性 EV 数量和 ASC 水平显著增加。与没有肺损伤的个体相比，有肺损伤的严重 TBI 患者的血清和血清源性 EV 中的 ASC 水平明显更高。只有来自头部创伤伴枪伤患者的 EV 具有神经来源。将血清源性 EV 递送至 HMVEC-L 激活了炎症小体并导致内皮细胞焦亡。因此，血清源性 EV 和炎症小体蛋白在 TBI 引起的肺损伤发病机制中起着关键作用，支持在 TBI 引起的肺损伤中激活 EV 介导的神经-呼吸炎症小体轴。
