Sturm Ramona, Heftrig David, Mörs Katharina, Wagner Nils, Kontradowitz Kerstin, Jurida Katrin, Marzi Ingo, Relja Borna
Department of Trauma, Hand and Reconstructive Surgery, University Hospital, Goethe University Frankfurt, 60590 Frankfurt, Germany.
Department of Trauma, Hand and Reconstructive Surgery, University Hospital, Goethe University Frankfurt, 60590 Frankfurt, Germany.
Immunobiology. 2017 Feb;222(2):301-307. doi: 10.1016/j.imbio.2016.09.010. Epub 2016 Sep 29.
Phagocytizing leukocytes (granulocytes and monocytes) play a fundamental role in immunological defense against pathogens and clearance of cellular debris after tissue injury due to trauma. According to the "two-hit hypothesis", phagocytes become primed due to/after trauma. Subsequently, a secondary stimulus may lead to their exaggerated response. This immune dysfunction can result in serious infectious complications, also depending on trauma injury pattern. Here, we investigated the phagocytizing capacity of leukocytes, and its correlation to trauma injury pattern.
MATERIAL/METHODS: Peripheral whole blood was taken daily from 29 severely injured trauma patients (TP, Injury Severity Score, ISS≥28) for ten days (1-10) following admission to the emergency department (ED). Sixteen healthy volunteers served as controls (HV). Samples were incubated with opsonized Staphylococcus aureus labelled with pHrodo fluorescent reagent and the percentage of phagocytizing activity was assessed by flow cytometry. Abbreviated Injury Scales (AIS)≥3 of head, chest and extremities were used for injury pattern analysis.
Overall distribution of active phagocytes (out of 100% phagocytizing leukocytes) in TP included granulocytes with 28.6±1.5% and monocytes with 59.3±1.9% at ED, and was comparable to HV (31.5±1.6% granulocytes and 60.1±1.6% monocytes). The percentage of phagocytizing granulocytes increased significantly after D2 (39.1±1.2%), while the percentage of phagocytizing monocytes (52.0±1.2%, p<0.05) decreased after D2. These changes persisted during the whole time course. Phagocytizing activity of granulocytes (27.9±2.8%) and monocytes (55.2±3.3%) was significantly decreased at ED compared to HV (42.4±4.1% and 78.1±3.1%, respectively). After D2 up to D10, phagocytizing activity was significantly enhanced in granulocytes. Phagocytizing activity of monocytes remained decreased on D1 and has risen continuously during the ten days time course to values comparable to HV. No significant differences in phagocytosis could be associated to certain injury pattern.
Our data demonstrate that the increasing percentage of phagocytizing granulocytes may indicate their enhanced mobilization out of bone marrow persisting until post-injury day 10. Furthermore, an initially decreased phagocytizing activity of granulocytes is strongly increased in the 10-days post-injury course. The altered activity of phagocytes due to injury could not be linked to any trauma injury pattern, and emerged rather as a general characteristic of phagocytes after severe trauma.
吞噬性白细胞(粒细胞和单核细胞)在针对病原体的免疫防御以及创伤所致组织损伤后细胞碎片的清除过程中发挥着重要作用。根据“二次打击假说”,吞噬细胞在创伤后或因创伤而处于预激活状态。随后,二次刺激可能导致其反应过度。这种免疫功能障碍可能会导致严重的感染并发症,其发生也取决于创伤损伤模式。在此,我们研究了白细胞的吞噬能力及其与创伤损伤模式的相关性。
材料/方法:从29例重伤创伤患者(TP,损伤严重度评分,ISS≥28)入院急诊部(ED)后的十天(第1 - 10天)每天采集外周全血。16名健康志愿者作为对照(HV)。样本与用pHrodo荧光试剂标记的经调理的金黄色葡萄球菌一起孵育,通过流式细胞术评估吞噬活性百分比。使用头部、胸部和四肢的简明损伤定级标准(AIS)≥3进行损伤模式分析。
TP中活性吞噬细胞(占100%吞噬性白细胞)的总体分布在ED时包括粒细胞占28.6±1.5%,单核细胞占59.3±1.9%,与HV相当(粒细胞占31.5±1.6%,单核细胞占60.1±1.6%)。吞噬性粒细胞百分比在第2天后显著增加(39.1±1.2%),而吞噬性单核细胞百分比在第2天后下降(52.0±1.2%,p<0.05)。这些变化在整个时间过程中持续存在。与HV相比,ED时粒细胞(27.9±2.8%)和单核细胞(55.2±3.3%)的吞噬活性显著降低(分别为42.4±4.1%和78.1±3.1%)。在第2天至第10天,粒细胞的吞噬活性显著增强。单核细胞的吞噬活性在第1天仍降低,并在十天时间过程中持续上升至与HV相当的值。吞噬作用方面无显著差异与特定损伤模式相关。
我们的数据表明,吞噬性粒细胞百分比的增加可能表明其从骨髓中的动员增强,这种增强一直持续到伤后第10天。此外,粒细胞最初降低的吞噬活性在伤后十天过程中大幅增加。因损伤导致的吞噬细胞活性改变与任何创伤损伤模式均无关联,而是作为严重创伤后吞噬细胞的一个普遍特征出现。