Lipopolysaccharide induction of tissue factor expression in rabbits
Lipopolysaccharide induction of tissue factor expression in rabbits
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DOI：
10.1128/iai.67.5.2540-2546.1999
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发表时间：
1999-05-01
影响因子：
3.1
通讯作者：
Mackman, N
中科院分区：
文献类型：
--
作者：
Erlich, J;Fearns, C;Mackman, N
组织因子（Tissue factor， TF）是凝血蛋白酶级联的主要激活因子，在败血症中具有致死性。尽管有一些研究分析了内毒素血症动物模型中TF的表达，但关于在不同组织中诱导表达TF的细胞类型仍然存在争议。在本研究中，我们对两种兔内毒素血症模型中TF mRNA和蛋白表达的诱导进行了详细分析，以更好地了解可能导致局部纤维蛋白沉积和弥散性血管内凝血的细胞类型。Northern blot分析显示，脂多糖（LPS）增加了TF在脑、肺和肾中的表达。原位杂交显示，在形态学上鉴定为肺上皮细胞和脑星形胶质细胞的细胞中，TF mRNA表达增加。在肾脏中，原位杂交实验和免疫组织化学分析显示，TF mRNA和蛋白在肾小球中表达升高，并在肾小管上皮中诱导表达。在lps处理的动物内皮细胞中，TF和vWF的双重染色未能显示TF的表达。这些结果表明，在LPS处理的家兔中，TF在许多不同类型的细胞中被诱导表达，这可能有助于内毒素血症时局部纤维蛋白沉积和组织损伤。
Tissue factor (TF) is the major activator of the coagulation protease cascade and contributes to lethality in sepsis, Despite several studies analyzing TF expression in animal models of endotoxemia, there remains debate about the cell types that are induced to express TF in different tissues. In this study, we performed a detailed analysis of the induction of TF mRNA and protein expression in two rabbit models of endotoxemia to better understand the cell types that may contribute to local fibrin deposition and disseminated intravascular coagulation. Northern blot analysis demonstrated that lipopolysaccharide (LPS) increased TF expression in the brain, lung, and kidney. In situ hybridization showed that TF mRNA expression was increased in cells identified morphologically as epithelial cells in the lung and as astrocytes in the brain. In the kidney, In situ hybridization experiments and immunohistochemical analysis showed that TF mRNA and protein expression was increased in renal glomeruli and induced in tubular epithelium. Dual staining for TF and vWF failed to demonstrate TF expression in endothelial cells in LPS-treated animals. These results demonstrate that TF expression is induced in many different cell types in LPS treated rabbits, which may contribute to local fibrin deposition and tissue injury during endotoxemia.