Curriculum in Toxicology and Environmental Medicine, North Carolina Jaycee Burn Center, Department of Surgery, Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Curriculum in Toxicology and Environmental Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Int J Mol Sci. 2021 Sep 18;22(18):10083. doi: 10.3390/ijms221810083.
Severe burn injury is a devastating form of trauma that results in persistent immune dysfunction with associated morbidity and mortality. The underlying drivers of this immune dysfunction remain elusive, and there are no prognostic markers to identify at-risk patients. Extracellular vesicles (EVs) are emerging as drivers of immune dysfunction as well as biomarkers. We investigated if EVs after burn injury promote macrophage activation and assessed if EV contents can predict length of hospital stay. EVs isolated early from mice that received a 20% total body surface area (TBSA) burn promoted proinflammatory responses in cultured splenic macrophages. Unbiased LC-MS/MS proteomic analysis of early EVs (<72 h post-injury) from mice and humans showed some similarities including enrichment of acute phase response proteins such as CRP and SAA1. Semi-unbiased assessment of early human burn patient EVs found alterations consistent with increased proinflammatory signaling and loss of inhibition of CRP expression. In a sample of 50 patients with large burn injury, EV SAA1 and CRP were correlated with TBSA injury in both sexes and were correlated with length of hospital stay in women. These findings suggest that EVs are drivers of immune responses after burn injury and their content may predict hospital course.
严重烧伤是一种毁灭性的创伤形式，会导致持续的免疫功能障碍，并伴有发病率和死亡率。这种免疫功能障碍的根本驱动因素仍不清楚，也没有预后标志物来识别高危患者。细胞外囊泡 (EVs) 作为免疫功能障碍的驱动因素和生物标志物正在出现。我们研究了烧伤后 EV 是否促进巨噬细胞激活，并评估了 EV 含量是否可以预测住院时间。从接受 20%总体表面积 (TBSA) 烧伤的小鼠中早期分离的 EV 促进了培养的脾巨噬细胞的促炎反应。对来自小鼠和人类的早期 EV（<72 小时伤后）进行的无偏见 LC-MS/MS 蛋白质组学分析显示出一些相似之处，包括急性反应蛋白（如 CRP 和 SAA1）的富集。对早期人类烧伤患者 EV 的半无偏见评估发现，与促炎信号增加和 CRP 表达抑制丧失一致的改变。在 50 名大面积烧伤患者的样本中，EV SAA1 和 CRP 在两性中均与 TBSA 损伤相关，并且与女性的住院时间相关。这些发现表明 EV 是烧伤后免疫反应的驱动因素，其含量可能预测住院过程。
