title: Tissue factor and tissue factor pathway inhibitor in nasal mucosa and nasal secretions of chronic rhinosinusitis with nasal polyp.
abstract: 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.
authors.affiliation: Department of Otorhinolaryngology, Shiga University of Medical Science, Otsu, Shiga, Japan.
authors.forename: Shino
authors.initials: S
authors.lastname: Shimizu
authors.forename: Takao
authors.initials: T
authors.lastname: Ogawa
authors.forename: Kumiko
authors.initials: K
authors.lastname: Takezawa
authors.forename: Ichiro
authors.initials: I
authors.lastname: Tojima
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kouzaki
authors.forename: Takeshi
authors.initials: T
authors.lastname: Shimizu
mesh_terms: D000328:Adult; D000368:Aged; D000990:Antithrombin III / Q000378:metabolism; D002478:Cells, Cultured; D002908:Chronic Disease; D004804:Eosinophils / Q000166:cytology; D004847:Epithelial Cells; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D006490:Hemostatics / Q000378:metabolism; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008074:Lipoproteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009077:Mucins / Q000378:metabolism; D009297:Nasal Mucosa / Q000378:metabolism* / Q000473:pathology; D009298:Nasal Polyps / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism; D011237:Predictive Value of Tests; D012220:Rhinitis / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D012680:Sensitivity and Specificity; D012852:Sinusitis / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D013917:Thrombin / Q000378:metabolism; D013925:Thromboplastin / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics*
chemical_list: D005819:Genetic Markers; D006490:Hemostatics; D008074:Lipoproteins; D009077:Mucins; C046193:antithrombin III-protease complex; C051928:lipoprotein-associated coagulation inhibitor; D007073:Immunoglobulin E; D000990:Antithrombin III; D013925:Thromboplastin; D010447:Peptide Hydrolases; D013917:Thrombin