PTX3 as a potential biomarker of acute lung injury: supporting evidence from animal experimentation
PTX3 as a potential biomarker of acute lung injury: supporting evidence from animal experimentation
复制标题
DOI：
10.1007/s00134-009-1720-0
复制
发表时间：
2010-02-01
影响因子：
38.9
通讯作者：
Liu, Mingyao
中科院分区：
文献类型：
--
作者：
He, Xiaolin;Han, Bing;Liu, Mingyao
在脓毒症或急性呼吸窘迫综合征患者中已发现长正五聚蛋白3（PTX 3）表达增加。组织因子（TF）活化在急性肺损伤的发病机制中起重要作用。本研究采用脂多糖（lipopolysaccharide，LPS）诱导小鼠急性肺损伤模型，观察肺组织中PTX 3表达、TF活化与肺损伤的关系。用抗人组织因子单克隆抗体治疗人组织因子基因敲入（hTF-KI）小鼠的肺损伤，Balb/c小鼠用递增剂量的LPS攻击。24 h后，支气管肺泡灌洗液中PTX 3蛋白水平随肺损伤程度增加而升高，并与组织因子（TF）活性相关。LPS（5 mg/kg）灌胃后6 h，进一步观察PTX 3和TF的表达和分布。在LPS攻击后6小时，用抗人TF单克隆抗体治疗显着减弱LPS诱导的肺损伤、肺泡纤维蛋白沉积和炎性细胞浸润。结论：PTX 3可能是反映肺损伤严重程度和提供有效治疗的生物标志物。PTX 3和TF之间的相互作用可能是介导肺损伤的潜在机制。
Increased expression of long pentraxin 3 (PTX3) has been found in patients with sepsis or acute respiratory distress syndrome. Tissue factor (TF) activation plays an important role in the pathogenesis of acute lung injury. The present study sought to determine the relationship between PTX3 expression and TF activation in acute lung injury.Lung injury was induced by intratracheal instillation of lipopolysaccharide (LPS) in mice, and the PTX3 expression, TF activation and lung injury were determined. We also treated the lung injury with an anti-human tissue factor monoclonal antibody in human tissue factor knock-in (hTF-KI) mice.Balb/c mice were challenged with increasing doses of LPS. After 24 h, PTX3 protein in the bronchioalveolar lavage fluid was increased in parallel with the severity of lung injury, and correlated with tissue factor (TF) activity. The expression and distribution of PTX3 and TF were further documented in detail 6 h after LPS (5 mg/kg) instillation. Treatment with anti-human TF monoclonal antibody dramatically attenuated LPS-induced lung injury, alveolar fibrin deposition and inflammatory cell infiltration in "humanized" hTF-KI mice 6 h after LPS challenge. The PTX3 expression was significantly decreased by the anti-coagulant therapy.These results support the clinical finding that PTX3 may be a useful biomarker to the reflect severity of lung injury and provide effective therapies. The interplay between PTX3 and TF could be a potential mechanism that mediates lung injury.