Yang Ce, Gao Jie, Dong Hong, Zhu Pei-Fang, Wang Zheng-Guo, Jiang Jian-Xin
State Key Laboratory of Trauma, Burns and Combined Injury, Department 4, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China.
J Trauma. 2008 Dec;65(6):1471-7. doi: 10.1097/TA.0b013e318166d279.
Previous studies in our laboratory have demonstrated the downregulation of surface expression of scavenger receptor (SR) and upregulation of CD14 in the presence of endotoxemia, which directly correlates to the excessive inflammatory response in lung injuries. This study aims to analyze the dynamics of the expressions of SR and CD14 in traumatic endotoxemia, and to investigate the receptor mechanism of immunomodulator, carboxymethyl-beta-1, 3-glucan (CMG), on the protection of traumatic infections.
By using a sublethal fracture plus endotoxemia model, experimental mice were assigned to sham group (Sham), trauma group (T), traumatic endotoxemia group (TE), and traumatic endotoxemia plus CMG group (TE + C). Alveolar macrophages were isolated from each group. Expressions of SR and CD14 were examined at the cell and tissue levels by immunohistochemistry assay. The effects of CMG on the phagocytosis of alveolar macrophages, tissue injury, and mortality were also determined.
Expressions of SR and CD14 in lungs and livers decreased and increased, respectively. Alteration of SR and CD14 levels was more evident in lungs than in livers in posttraumatic endotoxemia. CMG up-regulated the SR expression in lipopolysaccharide-stimulated alveolar macrophages, alleviated the tissue injury, reduced mice mortality, and increased the opsonin-independent phagocytosis of Staphylococcus aureus, which was inhibited by SR mono-antibody.
Significant correlation was found between inflammatory responses and the imbalance between SR and CD14 in posttraumatic endotoxemia. The more dramatic changes in lungs might be related to the sequential preferred injury in uncontrolled inflammation. CMG could be a promising bioactive reagent in immunomodulating sepsis.
我们实验室之前的研究表明，在内毒素血症存在的情况下，清道夫受体（SR）的表面表达下调，而CD14表达上调，这与肺损伤中过度的炎症反应直接相关。本研究旨在分析创伤性内毒素血症中SR和CD14表达的动态变化，并研究免疫调节剂羧甲基-β-1,3-葡聚糖（CMG）对创伤性感染的保护作用的受体机制。
采用亚致死性骨折加内毒素血症模型，将实验小鼠分为假手术组（Sham）、创伤组（T）、创伤性内毒素血症组（TE）和创伤性内毒素血症加CMG组（TE + C）。从每组中分离肺泡巨噬细胞。通过免疫组织化学分析在细胞和组织水平检测SR和CD14的表达。还测定了CMG对肺泡巨噬细胞吞噬作用、组织损伤和死亡率的影响。
肺和肝中SR和CD14的表达分别降低和升高。创伤后内毒素血症中，肺中SR和CD14水平的变化比肝中更明显。CMG上调脂多糖刺激的肺泡巨噬细胞中SR的表达，减轻组织损伤，降低小鼠死亡率，并增加金黄色葡萄球菌的非调理素依赖性吞噬作用，而SR单克隆抗体可抑制这种作用。
创伤后内毒素血症中炎症反应与SR和CD14失衡之间存在显著相关性。肺中更显著的变化可能与失控性炎症中的顺序性优先损伤有关。CMG可能是一种有前景的免疫调节脓毒症的生物活性试剂。
