Todoroki H, Nakamura S, Higure A, Okamoto K, Takeda S, Nagata N, Itoh H, Ohsato K
Department of Surgery 1, University of Occupational and Environmental Health, Kitakyushu, Japan.
Surgery. 2000 Feb;127(2):209-16. doi: 10.1067/msy.2000.103027.
Although tissue factor (TF) is involved in hemostasis, thrombogenesis, inflammation, and cellular immune response, its source in sepsis remains controversial. Recently, we found that, in addition to monocytes and endothelial cells, neutrophils may express TF in a rabbit model. The purpose of this study was to determine whether neutrophils could be a source of TF in a monkey model of sepsis.
TF messenger RNA (mRNA) and protein in neutrophils were assayed by in situ hybridization and immunohistochemistry in tissues obtained from monkeys after injection of lipopolysaccharide (LPS) (n = 3) and after injection of saline as a control (n = 2). Coagulation parameters were measured before and at 1.5 and 3 hours after injections.
In LPS-treated monkeys, TF mRNA and protein were induced not only in monocytes and endothelial cells, but also in neutrophils accumulating in the liver 3 hours after LPS injection. Thrombin-antithrombin III complex and fibrin degradation products D-dimer levels were significantly increased at 3 and 1.5 hours after LPS injection compared with controls.
Neutrophils are a source of TF and are implicated in direct activation of the coagulation cascade in the early phases of sepsis in the monkey. These results give important information for the treatment of sepsis.
尽管组织因子（TF）参与止血、血栓形成、炎症和细胞免疫反应，但其在脓毒症中的来源仍存在争议。最近，我们发现，在兔模型中，除单核细胞和内皮细胞外，中性粒细胞也可能表达TF。本研究的目的是确定在猴脓毒症模型中中性粒细胞是否可能是TF的来源。
通过原位杂交和免疫组织化学方法检测注射脂多糖（LPS）（n = 3）的猴及注射生理盐水作为对照（n = 2）的猴组织中中性粒细胞的TF信使核糖核酸（mRNA）和蛋白。在注射前及注射后1.5小时和3小时测量凝血参数。
在LPS处理的猴中，LPS注射3小时后，不仅单核细胞和内皮细胞中诱导产生TF mRNA和蛋白，而且肝脏中聚集的中性粒细胞也有诱导产生。与对照组相比，LPS注射后3小时和1.5小时凝血酶-抗凝血酶III复合物和纤维蛋白降解产物D-二聚体水平显著升高。
中性粒细胞是TF的来源，并且在猴脓毒症早期参与凝血级联反应的直接激活。这些结果为脓毒症的治疗提供了重要信息。
