title: Excessive fibrin deposition in nasal polyps caused by fibrinolytic impairment through reduction of tissue plasminogen activator expression.
abstract: BACKGROUND
  Nasal polyps (NPs) are characterized by intense edema or formation of pseudocysts filled with plasma proteins, mainly albumin. However, the mechanisms underlying NP retention of plasma proteins in their submucosa remain unclear.
  
  
  OBJECTIVE
  We hypothesized that formation of a fibrin mesh retains plasma proteins in NPs. We assessed the fibrin deposition and expression of the components of the fibrinolytic system in patients with chronic rhinosinusitis (CRS).
  
  
  METHODS
  We assessed fibrin deposition in nasal tissue from patients with CRS and control subjects by means of immunofluorescence. Fibrinolytic components, d-dimer, and plasminogen activators were measured using ELISA, real-time PCR, and immunohistochemistry. We also performed gene expression and protein quantification analysis in cultured airway epithelial cells.
  
  
  RESULTS
  Immunofluorescence data showed profound fibrin deposition in NP compared with uncinate tissue (UT) from patients with CRS and control subjects. Levels of the cross-linked fibrin cleavage product protein, d-dimer, were significantly decreased in NP compared with UT from patients with CRS and control subjects, suggesting reduced fibrinolysis (P < 0.05). Expression levels of tissue plasminogen activator (t-PA) mRNA and protein were significantly decreased in NP compared with UT from patients with CRS and control subjects (P < 0.01). Immunohistochemistry demonstrated clear reduction of t-PA in NP, primarily in the epithelium and glands. Th2 cytokine-stimulated cultured airway epithelial cells showed down-regulation of t-PA, suggesting a potential Th2 mechanism in NP.
  
  
  CONCLUSIONS
  A Th2-mediated reduction of t-PA might lead to excessive fibrin deposition in the submucosa of NP, which might contribute to the tissue remodeling and pathogenesis of CRS with nasal polyps.
authors.affiliation: Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Takabayashi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kato
authors.forename: Anju T
authors.initials: AT
authors.lastname: Peters
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Hulse
authors.forename: Lydia A
authors.initials: LA
authors.lastname: Suh
authors.forename: Roderick
authors.initials: R
authors.lastname: Carter
authors.forename: James
authors.initials: J
authors.lastname: Norton
authors.forename: Leslie C
authors.initials: LC
authors.lastname: Grammer
authors.forename: Seong H
authors.initials: SH
authors.lastname: Cho
authors.forename: Bruce K
authors.initials: BK
authors.lastname: Tan
authors.forename: Rakesh K
authors.initials: RK
authors.lastname: Chandra
authors.forename: David B
authors.initials: DB
authors.lastname: Conley
authors.forename: Robert C
authors.initials: RC
authors.lastname: Kern
authors.forename: Shigeharu
authors.initials: S
authors.lastname: Fujieda
authors.forename: Robert P
authors.initials: RP
authors.lastname: Schleimer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001798:Blood Proteins / Q000378:metabolism; D015536:Down-Regulation / Q000502:physiology; D004487:Edema / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism; D005260:Female; D005337:Fibrin / Q000378:metabolism*; D005342:Fibrinolysis / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D006801:Humans; D008297:Male; D008875:Middle Aged; D009297:Nasal Mucosa / Q000378:metabolism; D009298:Nasal Polyps / Q000378:metabolism*; D018418:Th2 Cells / Q000378:metabolism; D010959:Tissue Plasminogen Activator / Q000378:metabolism*; D055815:Young Adult
chemical_list: D001798:Blood Proteins; D005337:Fibrin; D010959:Tissue Plasminogen Activator