Differential expression of tissue factor mRNA and protein expression in murine sepsis - The role of the granulocyte revisited
Differential expression of tissue factor mRNA and protein expression in murine sepsis - The role of the granulocyte revisited
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DOI：
10.1160/th05-07-0512
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发表时间：
2006-02-01
影响因子：
6.7
通讯作者：
ten Cate, H
中科院分区：
文献类型：
--
作者：
de Waard, V;Hansen, HR;ten Cate, H
组织因子（TF）是一种跨膜蛋白，对凝血级联反应的启动至关重要。已报道TF在内毒素（脂多糖，LPS）介导的内毒素血症的进展中起重要作用，内毒素血症在许多组织中诱导，如肾、脾和肺。我们开发并验证了一种兔抗鼠TF肽抗血清，用于在鼠脓毒症模型中定位TF蛋白。TF蛋白分布进行了比较，TF mRNA和纤维蛋白沉积物，最终产生的促凝血TF活性的本地化。内毒素血症6小时后，在肾皮质-髓质交界处的肾小管区观察到明显的LPS介导的TF mRNA诱导，TF活性增加。然而，在脾脏中，TF mRNA在LPS注射后滤泡间区域被诱导，对应于同一区域TF蛋白的增加。脾脏中TF蛋白阳性细胞群主要为粒细胞，但在这些细胞内未观察到TF mRNA表达。基于这些观察结果和脾切除术后TF蛋白阳性粒细胞的存在，我们假设粒细胞摄取TF运输到其他位置，以启动纤维蛋白形成或诱导促炎基因表达后与因子VIIa的相互作用。
Tissue factor (TF) is a transmembrane protein,which is essential for initiation of the coagulation cascade. TF has been reported to play an important role in the progression of endotoxin (lipopolysaccharide, LPS)-mediated endotoxemia, being induced in numerous tissues, such as kidney, spleen and lung. We developed and validated a rabbit anti-murine TF peptide antiserum to localize TF protein in a murine sepsis model. TF protein distribution was compared to localization of TF mRNA and fibrin deposits, the ultimate resultant of procoagulant TF activity. Evident LPS-mediated TF mRNA induction was observed in the tubular area at the cortico-medullar junction in the kidney, and TF activity was increased after 6 hours of endotoxemia. In the spleen, however,TF mRNA was induced in the interfollicular region upon LPS injection, corresponding to increased TF protein in the same area. The clusters of TF-protein positive cells in the spleen are predominantly granulocytes, but no TF mRNA expression was observed within these cells. Based on these observations and the presence of TF-protein positive granulocytes after splenectomy,we hypothesize that granulocytes take-up TF for transport to other locations in order to initiate fibrin formation or to induce pro-inflammatory gene expression upon interaction with factor VIIa.