Trauma triggers a rapid innate immune response to aid the clearance of damaged/necrotic cells and their released damage-associated molecular pattern (DAMP). Here, we monitored the expression of EMR2/ADGRE2, involved in the functional regulation of innate immune cells, on circulating neutrophils in very severely and moderately/severely injured patients up to 240 h after trauma. Notably, neutrophilic EMR2 showed a uniform, injury severity- and type of injury-independent posttraumatic course in all patients. The percentage of EMR2+ neutrophils and their EMR2 level increased and peaked 48 h after trauma. Afterwards, they declined and normalized in some, but not all, patients. Circulating EMR2+ compared to EMR2− neutrophils express less CD62L and more CD11c, a sign of activation. Neutrophilic EMR2 regulation was verified in vitro. Remarkably, it increased, depending on extracellular calcium, in controls as well. Cytokines, enhanced in patients immediately after trauma, and sera of patients did not further affect this neutrophilic EMR2 increase, whereas apoptosis induction disrupted it. Likely the damaged/necrotic cells/DAMPs, unavoidable during neutrophil culture, stimulate the neutrophilic EMR2 increase. In summary, the rapidly increased absolute number of neutrophils, especially present in very severely injured patients, together with upregulated neutrophilic EMR2, may expand our in vivo capacity to react to and finally clear damaged/necrotic cells/DAMPs after trauma.

中文翻译：

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创伤后 GPCR EMR2/ADGRE2 对循环中性粒细胞粘附的增加与损伤严重程度无关

创伤会触发快速的先天免疫反应，以帮助清除受损/坏死的细胞及其释放的损伤相关分子模式 (DAMP)。在这里，我们监测了极重度和中度/重度损伤患者循环中性粒细胞中 EMR2/ADGRE2 的表达，参与先天免疫细胞的功能调节，直至创伤后 240 小时。值得注意的是，所有患者的中性粒细胞 EMR2 表现出一致的、与损伤严重程度和类型无关的创伤后病程。EMR2+中性粒细胞的百分比及其EMR2水平增加并在创伤后48小时达到峰值。之后，一些（但不是全部）患者的症状下降并恢复正常。与 EMR2− 相比，循环 EMR2+ 中性粒细胞表达较少的 CD62L 和更多的 CD11c，这是激活的标志。中性粒细胞 EMR2 调节已在体外得到验证。值得注意的是，在对照组中，它的增加也取决于细胞外钙。创伤后患者体内立即增强的细胞因子和患者血清并没有进一步影响中性粒细胞 EMR2 的增加，而细胞凋亡诱导则破坏了这种增加。中性粒细胞培养过程中不可避免的受损/坏死细胞/DAMP 可能会刺激中性粒细胞 EMR2 增加。总之，中性粒细胞绝对数量的迅速增加，尤其是在严重受伤的患者中，加上中性粒细胞 EMR2 的上调，可能会扩大我们体内对创伤后受损/坏死细胞/DAMP 做出反应并最终清除的能力。