Local activation of the tissue factor-factor VIIa pathway in patients with pneumonia and the effect of inhibition of this pathway in murine pneumococcal pneumonia
Local activation of the tissue factor-factor VIIa pathway in patients with pneumonia and the effect of inhibition of this pathway in murine pneumococcal pneumonia
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DOI：
10.1097/01.ccm.0000218807.20570.c2
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发表时间：
2006-06-01
影响因子：
8.8
通讯作者：
van der Poll, Tom
中科院分区：
文献类型：
--
作者：
Rijneveld, Anita W.;Weijer, Sebastiaan;van der Poll, Tom
目的：组织因子（TF）-因子VIIa（FVIIa）复合物不仅是激活凝血功能所必需的，而且还影响脓毒症时的炎症反应。本研究的目的是确定TF-FVIIa在肺炎链球菌引起的肺炎中的作用，肺炎链球菌是社区获得性肺炎中最重要的致病微生物，也是败血症的主要原因。设计：一项对照的体内实验室研究。患者和受试者，单侧社区获得性肺炎患者和雌性BALB/c小鼠。社区获得性肺炎患者行双侧支气管肺泡灌洗。在小鼠中，通过鼻内接种S.测量和主要结果：单侧社区获得性肺炎患者显示，与未感染部位相比，从感染部位获得的支气管肺泡灌洗液中FVIIa、可溶性TF和凝血酶-抗凝血酶复合物浓度升高。小鼠感染S.肺炎性肺炎显示肺中TF表达和纤维蛋白沉积增加以及支气管肺泡灌洗液中凝血酶-抗凝血酶复合物水平升高; rNAPc 2抑制TF-FVIIa减弱肺中的促凝血反应，但不影响宿主防御，如肺炎球菌的生长和存活不变所反映的。这些数据表明，TF-FVIIa活性有助于肺炎球菌肺炎期间肺部凝血的激活，但在该小鼠模型中，nut在抗菌宿主防御中是否发挥重要作用。
Objective: The tissue factor (TF)-factor Vila (FVIIa) complex not only is essential for activation of blood coagulation but also affect the inflammatory response during sepsis. The objective of this study was to determine the role of TF-FVIIa in pneumonia caused by Streptiococcus pneumoniae, the most important causative organism in community-acquired pneumonia and a major cause of sepsis.Design: A controlled, in vivo laboratory study.Setting: Research laboratory of a health sciences university. Patients and Subjects.,Patients with unilateral community-acquired pneumonia and female BALB/c mice.Interventions. Bilateral bronchoalveolar lavage was performed in patents with community-acquired pneumonia. In mice, pneumonia was induced by intranasal inoculation with S. pneumoniae with or without concurrent inhibition of TF-FVIIa by subcutaneous injections of recombinant nematode anticoagulant protein (rNAPc2).Measurements and Main Results: Patients with unilateral community-acquired pneumonia demonstrated elevated concentrations of FVIIa, soluble TF, and thrombin-antithrombin complexes in bronchoalveolar lavage fluid obtained from the infected site compared with the uninfected site. Mice with S. pneumoniae pneumonia displayed increased TF expression and fibrin deposits in lungs together with elevated thrombin-antithrombin complex levels in bronchoalveolar lavage fluid; inhibition of TF-FVIIa by rNAPc2 attenuated the procoagulant response in the lung but did not affect host defense, as reflected by an unaltered outgrowth of pneumococci and an unchanged survival.Conclusions., These data suggest that TF-FVIIa activity contributes to activation of coagulation in the lung during pneumococcal pneumonia but does nut play an important role in the antibacterial host defense in this murine model.