Erlich J, Fearns C, Mathison J, Ulevitch R J, Mackman N
Departments of Immunology and Vascular Biology, The Scripps Research Institute, La Jolla, California, USA.
Infect Immun. 1999 May;67(5):2540-6. doi: 10.1128/IAI.67.5.2540-2546.1999.
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.
组织因子（TF）是凝血蛋白酶级联反应的主要激活剂，在脓毒症致死过程中起作用。尽管有多项研究分析了内毒素血症动物模型中TF的表达情况，但对于不同组织中被诱导表达TF的细胞类型仍存在争议。在本研究中，我们对两种内毒素血症兔模型中TF mRNA和蛋白表达的诱导情况进行了详细分析，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印迹分析表明，脂多糖（LPS）可增加脑、肺和肾中TF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表明，TF mRNA和蛋白表达在肾小球中增加，并在肾小管上皮细胞中诱导表达。TF和vWF的双重染色未能在LPS处理动物的内皮细胞中显示TF表达。这些结果表明，在LPS处理的兔中，许多不同细胞类型均可诱导TF表达，这可能在内毒素血症期间导致局部纤维蛋白沉积和组织损伤。
