Hematopoietic and nonhematopoietic cell tissue factor activates the coagulation cascade in endotoxemic mice
Hematopoietic and nonhematopoietic cell tissue factor activates the coagulation cascade in endotoxemic mice
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DOI：
10.1182/blood-2009-12-259267
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发表时间：
2010-08-05
期刊：
影响因子：
20.3
通讯作者：
Mackman, Nigel
中科院分区：
文献类型：
--
作者：
Pawlinski, Rafal;Wang, Jian-Guo;Mackman, Nigel
组织因子（TF）是凝血级联反应的主要激活剂。在内毒素血症期间，TF表达导致弥散性血管内凝血。然而，不同类型细胞表达TF对凝血激活的相对贡献尚未确定。在这项研究中，我们研究了选择性抑制TF表达或TF基因（F3）的细胞类型特异性缺失对内毒素血症小鼠模型凝血激活的影响。我们发现，抑制TF对造血或非造血细胞降低血浆凝血酶-抗凝血酶（达特）水平8小时后，管理的细菌脂多糖（LPS）。此外，在骨髓细胞（TFflox/flox，LysM（Cre）小鼠）或内皮细胞（EC）和造血细胞（TFflox/flox，Tie-2（Cre）小鼠）中缺乏TF基因的内毒素血症小鼠中，血浆达特水平显著降低。然而，单独缺失内皮细胞中的TF基因对LPS诱导的血浆达特水平没有影响。在血管平滑肌细胞中缺乏TF的小鼠中观察到类似的结果。最后，我们发现小鼠血小板不表达TF前mRNA或mRNA。我们的数据表明，在小鼠内毒素血症模型中，凝血级联反应的激活是由髓系细胞和未鉴定的非造血细胞类型表达的TF启动的。（血。2010;116（5）：806-814）
Tissue factor (TF) is the primary activator of the coagulation cascade. During endo-toxemia, TF expression leads to disseminated intravascular coagulation. However, the relative contribution of TF expression by different cell types to the activation of coagulation has not been defined. In this study, we investigated the effect of either a selective inhibition of TF expression or cell type-specific deletion of the TF gene (F3) on activation of coagulation in a mouse model of endotoxemia. We found that inhibition of TF on either hematopoietic or nonhematopoietic cells reduced plasma thrombin-antithrombin (TAT) levels 8 hours after administration of bacterial lipopolysaccharide (LPS). In addition, plasma TAT levels were significantly reduced in endotoxemic mice lacking the TF gene in either myeloid cells (TFflox/flox, LysM(Cre) mice) or in both endothelial cells (ECs) and hematopoietic cells (TFflox/flox, Tie-2(Cre) mice). However, deletion of the TF gene in ECs alone had no effect on LPS-induced plasma TAT levels. Similar results were observed in mice lacking TF in vascular smooth muscle cells. Finally, we found that mouse platelets do not express TF pre-mRNA or mRNA. Our data demonstrate that in a mouse model of endotoxemia activation of the coagulation cascade is initiated by TF expressed by myeloid cells and an unidentified nonhematopoietic cell type(s). (Blood. 2010;116(5):806-814)