Amara Umme, Kalbitz Miriam, Perl Mario, Flierl Michael A, Rittirsch Daniel, Weiss Manfred, Schneider Marion, Gebhard Florian, Huber-Lang Markus
Department of Traumatology, Hand, Plastic and Reconstructive Surgery, University Hospital Ulm, Germany.
Shock. 2010 Jun;33(6):568-75. doi: 10.1097/SHK.0b013e3181c799d4.
As a crucial element of innate immunity, the complement cascade becomes activated after severe trauma. Regulation of the complement cascade and protection against complement-mediated tissue destruction is provided by a selection of soluble and membrane-bound complement regulatory proteins (CRegs). To date, the leukocyte expression profile of CRegs in multiple injured patients is unknown. In the present study, expression of CRegs and the C5a receptor (CD88) was analyzed on neutrophils, monocytes, and lymphocytes by flow cytometry. Whole blood samples were obtained from healthy volunteers (n = 16) or multiple injured patients (n = 12) on admission in the emergency department and 4, 12, 24, 120, and 240 h after trauma. The content of CRegs and CD88 on leukocytes was significantly altered posttrauma: CD55 (decay accelerating factor) displayed a time-dependent, elevated expression pattern on neutrophils and monocytes, but not on lymphocytes. CD59 (membrane attack complex inhibitor) expression was significantly increased on neutrophils and monocytes at the time of admission and after 5 to 10 days in lymphocytes. CD46 (membrane cofactor protein) was significantly down-regulated in all three cell types posttrauma. CD35 (complement receptor 1) expression on neutrophils was initially decreased, whereas monocytes presented a significant increase in CD35 expression. CD35 on lymphocyte remained unchanged throughout the observation period. CD88 expression was considerably reduced on leukocytes between 0 and 240 h after injury. CD59, CD46, and CD88 expression values on neutrophils reversely correlated with severity of injury. In summary, expression profiles of CRegs and CD88 on leukocytes are specifically altered after polytrauma in humans, indicating a trauma-induced "complementopathy."
作为固有免疫的关键要素，补体级联反应在严重创伤后被激活。一系列可溶性和膜结合补体调节蛋白（CRegs）可对补体级联反应进行调节，并防止补体介导的组织破坏。迄今为止，多发伤患者中CRegs的白细胞表达谱尚不清楚。在本研究中，通过流式细胞术分析了中性粒细胞、单核细胞和淋巴细胞上CRegs及C5a受体（CD88）的表达。在急诊科对健康志愿者（n = 16）或多发伤患者（n = 12）入院时以及创伤后4、12、24、120和240小时采集全血样本。创伤后白细胞上CRegs和CD88的含量发生了显著变化：CD55（衰变加速因子）在中性粒细胞和单核细胞上呈现出随时间依赖性升高的表达模式，但在淋巴细胞上未出现此现象。CD59（膜攻击复合物抑制剂）在入院时中性粒细胞和单核细胞上的表达显著增加，在淋巴细胞中则在5至10天后增加。创伤后所有三种细胞类型中CD46（膜辅因子蛋白）均显著下调。中性粒细胞上CD35（补体受体1）的表达最初下降，而单核细胞中CD35表达显著增加。淋巴细胞上的CD35在整个观察期内保持不变。损伤后0至240小时白细胞上CD88的表达显著降低。中性粒细胞上CD59、CD46和CD88的表达值与损伤严重程度呈负相关。总之，多发伤后人白细胞上CRegs和CD88的表达谱发生了特异性改变，表明存在创伤诱导的“补体病”。
