title: Increased expression of factor XIII-A in patients with chronic rhinosinusitis with nasal polyps.
abstract: BACKGROUND
  Profound edema or formation of a pseudocyst containing plasma proteins is a prominent characteristic of nasal polyps (NP). However, the mechanisms underlying NP retention of plasma proteins in the submucosa remain unclear. Recently, we reported that impairment of fibrinolysis causes excessive fibrin deposition in NP and this might be involved in the retention of plasma proteins. Although the coagulation cascade plays a critical role in fibrin clot formation at extravascular sites, the expression and role of coagulation factors in NP remain unclear.
  
  
  OBJECTIVE
  The objective of this study was to investigate the expression of coagulation factors in patients with chronic rhinosinusitis (CRS).
  
  
  METHODS
  Sinonasal tissues were collected from patients with CRS and control subjects. We assayed mRNA for factor XIII-A (FXIII-A) by using real-time PCR and measured FXIII-A protein by means of ELISA, immunohistochemistry, and immunofluorescence.
  
  
  RESULTS
  FXIII-A mRNA levels were significantly increased in NP tissue from patients with CRS with NP (P < .001) compared with uncinate tissue from patients with CRS or control subjects. Similarly, FXIII-A protein levels were increased in NP. Immunofluorescence analysis revealed that FXIII-A expression in inflammatory cells and FXIII-A(+) cell numbers were significantly increased in NP. Most FXIII-A staining was observed within CD68(+)/CD163(+) M2 macrophages in NP. Levels of FXIII-A correlated with markers of M2 macrophages, suggesting that M2 macrophages are major FXIIIA-producing cells in NP.
  
  
  CONCLUSIONS
  Overproduction of FXIII-A by M2 macrophages might contribute to the excessive fibrin deposition in the submucosa of NP, which might contribute to the tissue remodeling and pathogenesis of CRS with NP.
authors.affiliation: Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill; Division of Otorhinolaryngology Head and Neck Surgery, Department of Sensory and Locomotor Medicine, University of Fukui, Fukui, Japan.
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Takabayashi
authors.affiliation: Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kato
authors.affiliation: Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill.
authors.forename: Anju T
authors.initials: AT
authors.lastname: Peters
authors.affiliation: Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill.
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Hulse
authors.affiliation: Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill.
authors.forename: Lydia A
authors.initials: LA
authors.lastname: Suh
authors.affiliation: Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill.
authors.forename: Roderick
authors.initials: R
authors.lastname: Carter
authors.affiliation: Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill.
authors.forename: James
authors.initials: J
authors.lastname: Norton
authors.affiliation: Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill.
authors.forename: Leslie C
authors.initials: LC
authors.lastname: Grammer
authors.affiliation: Department of Otolaryngology, Northwestern University Feinberg School of Medicine, Chicago, Ill.
authors.forename: Bruce K
authors.initials: BK
authors.lastname: Tan
authors.affiliation: Department of Otolaryngology, Northwestern University Feinberg School of Medicine, Chicago, Ill.
authors.forename: Rakesh K
authors.initials: RK
authors.lastname: Chandra
authors.affiliation: Department of Otolaryngology, Northwestern University Feinberg School of Medicine, Chicago, Ill.
authors.forename: David B
authors.initials: DB
authors.lastname: Conley
authors.affiliation: Department of Otolaryngology, Northwestern University Feinberg School of Medicine, Chicago, Ill.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Kern
authors.affiliation: Division of Otorhinolaryngology Head and Neck Surgery, Department of Sensory and Locomotor Medicine, University of Fukui, Fukui, Japan.
authors.forename: Shigeharu
authors.initials: S
authors.lastname: Fujieda
authors.affiliation: Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill; Department of Otolaryngology, Northwestern University Feinberg School of Medicine, Chicago, Ill. Electronic address: rpschleimer@northwestern.edu.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Schleimer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002908:Chronic Disease; D026122:Factor XIIIa / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009298:Nasal Polyps / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D012220:Rhinitis / Q000378:metabolism*; D012852:Sinusitis / Q000378:metabolism*; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D012333:RNA, Messenger; D026122:Factor XIIIa
keywords: CRS; CRS with nasal polyps; CRS without nasal polyps; CRSsNP; CRSwNP; Chronic rhinosinusitis; FXIII-A; FXIII-B; Factor XIII-A; Factor XIII-B; M2 macrophages; MMR; Macrophage mannose receptor; NP; Nasal polyps; STAB1; Stabilin 1; Tissue plasminogen activator; UT; Uncinate tissue; coagulation cascade; factor XIII-A (FXIII-A); fibrin; nasal polyps; t-PA
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