Neutrophils are vital to both the inflammatory cascade and tissue repair after an injury. Neutrophil heterogeneity is well established but there is less evidence for significant, different functional roles for neutrophil subsets. OLFM4 (Olfactomedin-4) is expressed by a subset of neutrophils, and high expression of OLFM4 is associated with worse outcomes in patients with sepsis and acute respiratory distress syndrome. We hypothesized that an increased number of OLFM4⁺ neutrophils would occur in trauma patients with worse clinical outcomes. To test this, we prospectively enrolled patients who suffered a blunt traumatic injury. Blood was collected at the time of admission, Day 3, and Day 7 and analyzed for the percentage of neutrophils expressing OLFM4. We found that a subset of patients who suffered blunt traumatic injury upregulated their percentage of OLFM4⁺ neutrophils. Those who upregulated their OLFM4 had an increased length of stay, days in the ICU, and ventilator days. A majority of these patients also suffered from hemorrhagic shock. To establish a potential role for OLFM4⁺ neutrophils, we used a murine model of hemorrhagic shock because mice also express OLFM4 in a subset of neutrophils. These studies demonstrated that wild type mice had higher concentrations of cytokines in the plasma and myeloperoxidase in the lungs compared with OLFM4-null mice. In addition, we used an anti-OLFM4 antibody, which when given to wild type mice led to the reduction of myeloperoxidase in the lungs of mice. These findings suggest that OLFM4⁺ neutrophils are a unique subset of neutrophils that affect the inflammatory response after tissue injury.

中性粒细胞对于损伤后的炎症级联反应和组织修复都至关重要。中性粒细胞异质性已得到充分证实，但中性粒细胞亚群的显着不同功能作用的证据较少。OLFM4 (Olfactomedin-4) 由一部分中性粒细胞表达，OLFM4的高表达与脓毒症和急性呼吸窘迫综合征患者的不良预后相关。我们假设增加的 OLFM4 ⁺中性粒细胞会出现在临床结果较差的创伤患者中。为了测试这一点，我们前瞻性地招募了遭受钝性外伤的患者。在入院时、第 3 天和第 7 天采集血液，并分析表达 OLFM4 的中性粒细胞的百分比。我们发现，一部分遭受钝性外伤的患者上调了 OLFM4 ⁺中性粒细胞的百分比。那些上调 OLFM4 的人住院时间、ICU 天数和呼吸机天数增加。这些患者中的大多数还患有失血性休克。为 OLFM4 ^{+建立潜在角色}中性粒细胞，我们使用小鼠失血性休克模型，因为小鼠也在中性粒细胞亚群中表达 OLFM4。这些研究表明，与 OLFM4 缺失小鼠相比，野生型小鼠血浆中的细胞因子和肺中的髓过氧化物酶浓度更高。此外，我们使用了一种抗 OLFM4 抗体，当给予野生型小鼠时，它会导致小鼠肺部的髓过氧化物酶减少。这些发现表明 OLFM4 ⁺中性粒细胞是影响组织损伤后炎症反应的独特中性粒细胞亚群。