Shimizu Shino, Ogawa Takao, Takezawa Kumiko, Tojima Ichiro, Kouzaki Hideaki, Shimizu Takeshi
Department of Otorhinolaryngology, Shiga University of Medical Science, Otsu, Shiga, Japan.
Am J Rhinol Allergy. 2015 Jul-Aug;29(4):235-42. doi: 10.2500/ajra.2015.29.4183.
Activation of the coagulation system with an increase in thrombin generation is involved in the pathogenesis of tissue remodeling in chronic rhinosinusitis (CRS). Tissue factor (TF) is an important protein for initiation of the extrinsic coagulation pathway, and TF pathway inhibitor (TFPI) is a regulator of TF-induced coagulation. This study was conducted to elucidate the roles of TF and TFPI in the pathogenesis of CRS.
Tissue localization of TF, TFPI, and fibrin was determined by immunostaining of nasal polyps and inferior turbinates obtained during endonasal surgery in patients with CRS with nasal polyp (CRSwNP). Nasal secretions were collected from patients with CRSwNP, allergic rhinitis, and from control patients. The concentrations of TF and TFPI were measured in nasal secretions from each group. The concentrations of TF and TFPI released into culture medium by normal human nasal epithelial cells treated with thrombin, protease-activated receptor 1 agonist peptide, or tumor necrosis factor α were also measured.
TF expression was localized in nasal epithelial cells and in infiltrating eosinophils of nasal mucosa. TFPI expression was localized in nasal epithelial cells, and fibrin deposition was observed in nasal secretions and the lamina propria of nasal polyps. Nasal secretions contained significant concentrations of TF and TFPI. The concentration of TFPI in nasal secretions correlated positively with thrombin activity and the concentration of thrombin-antithrombin III complex. Treatment with thrombin, protease-activated receptor 1 agonist peptide, or tumor necrosis factor α stimulated significant release of TF and TFPI from cultured nasal epithelial cells.
By upregulating the coagulation system, TF and TFPI play an important role in the pathogenesis of CRSwNP.
凝血系统激活伴凝血酶生成增加参与慢性鼻-鼻窦炎（CRS）组织重塑的发病机制。组织因子（TF）是启动外源性凝血途径的重要蛋白质，而组织因子途径抑制剂（TFPI）是TF诱导凝血的调节剂。本研究旨在阐明TF和TFPI在CRS发病机制中的作用。
通过对CRS伴鼻息肉（CRSwNP）患者鼻内镜手术中获取的鼻息肉和下鼻甲进行免疫染色，确定TF、TFPI和纤维蛋白的组织定位。收集CRSwNP患者、变应性鼻炎患者及对照患者的鼻腔分泌物。测定每组鼻腔分泌物中TF和TFPI的浓度。还测定了经凝血酶、蛋白酶激活受体1激动肽或肿瘤坏死因子α处理的正常人鼻上皮细胞释放到培养基中的TF和TFPI浓度。
TF表达定位于鼻黏膜上皮细胞和浸润的嗜酸性粒细胞。TFPI表达定位于鼻黏膜上皮细胞，在鼻腔分泌物和鼻息肉固有层观察到纤维蛋白沉积。鼻腔分泌物中含有显著浓度的TF和TFPI。鼻腔分泌物中TFPI浓度与凝血酶活性及凝血酶-抗凝血酶III复合物浓度呈正相关。凝血酶、蛋白酶激活受体1激动肽或肿瘤坏死因子α处理可刺激培养的鼻上皮细胞显著释放TF和TFPI。
通过上调凝血系统，TF和TFPI在CRSwNP的发病机制中起重要作用。
