Tissue factor deficiency increases alveolar hemorrhage and death in influenza A virus-infected mice.

Tissue factor deficiency increases alveolar hemorrhage and death in influenza A virus-infected mice.
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DOI:
10.1111/jth.13307
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发表时间:
2016-06
期刊:
Journal of thrombosis and haemostasis : JTH
影响因子:
--
通讯作者:
Mackman N
Mackman N
中科院分区:
其他
文献类型:
--
作者:
Antoniak S;Tatsumi K;Hisada Y;Milner JJ;Neidich SD;Shaver CM;Pawlinski R;Beck MA;Bastarache JA;Mackman N

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甲型流感病毒 (IAV) 感染是一种常见的呼吸道感染,在全世界范围内造成相当大的发病率和死亡率。研究组织因子 (TF) 遗传缺陷对甲型流感感染小鼠模型的影响。野生型小鼠、低组织因子 (LTF) 小鼠和不同细胞类型中 TF 基因缺失的小鼠均被小鼠适应的 A/Puerto Rico/8/34 H1N1 IAV 株感染。测量肺部的TF表达,收集支气管肺泡灌洗液(BALF)以测量细胞外囊泡TF、凝血激活、肺泡出血和炎症。野生型小鼠的IAV感染增加了肺TF的表达,激活了BALF中的凝血和炎症,同时也导致了肺泡出血。 LTF小鼠和肺上皮细胞TF选择性缺陷小鼠的TF基础水平较低,感染后未能增加TF表达;与对照组相比,这两种小鼠品系出现更多的肺泡出血和死亡。相反,删除骨髓细胞或内皮细胞和造血细胞中的 TF 并不会增加 IAV 感染后的肺泡出血或死亡。这些结果表明,肺中尤其是上皮细胞中的 TF 表达是 IAV 感染后维持肺泡止血所必需的。我们的研究表明,需要 TF 依赖性凝血激活来限制甲型流感感染后的肺泡出血和死亡。
Influenza A virus (IAV) infection is a common respiratory tract infection that causes considerable morbidity and mortality worldwide. To investigate the effect of a genetic deficiency of tissue factor (TF) in a mouse model of influenza A infection. Wild-type mice, low tissue factor (LTF) mice and mice with the TF gene deleted in different cell types were infected with a mouse-adapted A/Puerto Rico/8/34 H1N1 strain of IAV. TF expression was measured in the lungs, and bronchoalveolar lavage fluid (BALF) was collected to measure extracellular vesicle TF, activation of coagulation, alveolar hemorrhage and inflammation. IAV infection of wild-type mice increased lung TF expression, activation of coagulation and inflammation in the BALF, but also led to alveolar hemorrhage. LTF mice and mice with a selective deficiency of TF in lung epithelial cells had low basal levels of TF and failed to increase TF expression after infection; these two strains of mice had more alveolar hemorrhage and death compared with controls. In contrast, deletion of TF in either myeloid cells or endothelial cells and hematopoietic cells did not increase alveolar hemorrhage or death after IAV infection. These results indicate that TF expression in the lung, particularly in epithelial cells, is required to maintain alveolar hemostasis after IAV infection. Our study indicates that TF-dependent activation of coagulation is required to limit alveolar hemorrhage and death after influenza A infection.
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