Background: 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.
Methods: 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.
Results: 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.
Conclusions: By upregulating the coagulation system, TF and TFPI play an important role in the pathogenesis of CRSwNP.