Fang Catherine W H, Yao Yong-Ming, Shi Zhi-Guo, Yu Yan, Wu Ye, Lu Lian-Rong, Sheng Zhi-Yong
Department of Microbiology and Immunology, Trauma Research Center, Postgraduate Medical College, Beijing, People's Republic of China.
J Trauma. 2002 Nov;53(5):957-67. doi: 10.1097/00005373-200211000-00024.
We hypothesized that lipopolysaccharide-binding protein (LBP) and lipopolysaccharide receptor CD14 would present a pair of key molecules in pathophysiologic alterations induced by low concentrations of endotoxin after trauma. The aim of this study was to investigate the relationship between endotoxin translocation and tissue LBP/CD14 messenger ribonucleic acid (mRNA) expression after burn injury, and to define the potential role of LBP/CD14 in mediating inflammatory mediator induction, as well as the pathogenesis of organ damage.
Wistar rats were subjected to a 35% full-thickness scald injury, and tissue samples from liver, kidneys, lungs, and intestine were collected to measure LBP/CD14 and tumor necrosis factor-alpha (TNF-alpha) mRNA expression. Peritoneal macrophages were harvested by peritoneal lavage to determine CD14 mRNA expression.
It was found that endotoxin levels in liver, spleen, and lung increased markedly after thermal injury, with the highest level in liver. Both tissue LBP and CD14 mRNA expression increased markedly after burns, peaking at 12 hours, and then decreasing gradually. At 48 hours, LBP gene expression had a tendency to the baseline level, whereas CD14 mRNA expression increased again. Likewise, CD14 mRNA levels were up-regulated markedly in peritoneal macrophages. Conversely, gene expression of TNF-alpha in tissues elevated markedly after acute insults. There were positive correlations between lipopolysaccharide levels and LBP/CD14 mRNA as well as TNF-alpha mRNA expression in tissues. Similar results were also obtained between CD14, TNF-alpha mRNA expression in liver tissue and liver function parameters, and between pulmonary TNF-alpha mRNA and myeloperoxidase activities (p < 0.01).
Thermal injury per se can markedly up-regulate both LBP and CD14 gene expression in various organs. Excessive LBP and CD14 mRNA expression might be associated with enhanced synthesis and release of TNF-alpha stimulated by endotoxin translocation after major burns.
我们推测脂多糖结合蛋白（LBP）和脂多糖受体CD14是创伤后低浓度内毒素诱导的病理生理改变中的一对关键分子。本研究旨在探讨烧伤后内毒素移位与组织LBP/CD14信使核糖核酸（mRNA）表达之间的关系，并确定LBP/CD14在介导炎症介质诱导以及器官损伤发病机制中的潜在作用。
将Wistar大鼠进行35%全层烫伤，收集肝脏、肾脏、肺和肠道的组织样本以检测LBP/CD14和肿瘤坏死因子-α（TNF-α）mRNA表达。通过腹腔灌洗收集腹腔巨噬细胞以测定CD14 mRNA表达。
发现热损伤后肝脏、脾脏和肺中的内毒素水平显著升高，其中肝脏中的水平最高。烧伤后组织LBP和CD14 mRNA表达均显著增加，在12小时达到峰值，然后逐渐下降。在48小时时，LBP基因表达有恢复至基线水平的趋势，而CD1 mRNA表达再次升高。同样，腹腔巨噬细胞中的CD14 mRNA水平也显著上调。相反，急性损伤后组织中TNF-α的基因表达显著升高。组织中脂多糖水平与LBP/CD14 mRNA以及TNF-α mRNA表达之间存在正相关。在肝组织中CD14、TNF-α mRNA表达与肝功能参数之间，以及肺组织中TNF-α mRNA与髓过氧化物酶活性之间也获得了相似的结果（p<0.01）。
热损伤本身可显著上调各器官中LBP和CD14基因的表达。LBP和CD14 mRNA的过度表达可能与严重烧伤后内毒素移位刺激TNF-α的合成和释放增加有关。
