Increased expression of factor XIII-A in patients with chronic rhinosinusitis with nasal polyps

Tetsuji Takabayashi, Atsushi Kato, Anju T. Peters, Kathryn E. Hulse, Lydia A. Suh, Roderick Carter, James Norton, Leslie C. Grammer, Bruce K. Tan, Rakesh K. Chandra, David B. Conley, Robert C. Kern, Shigeharu Fujieda, Robert P. Schleimer*

*Corresponding author for this work

Research output: Contribution to journalArticle

39 Citations (Scopus)

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. Conclusion: 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.

Original languageEnglish (US)
JournalJournal of Allergy and Clinical Immunology
Volume132
Issue number3
DOIs
StatePublished - Jan 1 2013

Fingerprint

Factor XIII
Nasal Polyps
Fibrin
Macrophages
Blood Proteins
Blood Coagulation Factors
Fluorescent Antibody Technique
Messenger RNA
Fibrinolysis
Real-Time Polymerase Chain Reaction
Edema
Proteins

Keywords

  • Chronic rhinosinusitis
  • M2 macrophages
  • coagulation cascade
  • factor XIII-A (FXIII-A)
  • fibrin
  • nasal polyps

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

@article{46547d2110ab4425bcf45f6df2db9319,
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. Conclusion: 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.",
keywords = "Chronic rhinosinusitis, M2 macrophages, coagulation cascade, factor XIII-A (FXIII-A), fibrin, nasal polyps",
author = "Tetsuji Takabayashi and Atsushi Kato and Peters, {Anju T.} and Hulse, {Kathryn E.} and Suh, {Lydia A.} and Roderick Carter and James Norton and Grammer, {Leslie C.} and Tan, {Bruce K.} and Chandra, {Rakesh K.} and Conley, {David B.} and Kern, {Robert C.} and Shigeharu Fujieda and Schleimer, {Robert P.}",
year = "2013",
month = "1",
day = "1",
doi = "10.1016/j.jaci.2013.02.003",
language = "English (US)",
volume = "132",
journal = "Journal of Allergy and Clinical Immunology",
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Increased expression of factor XIII-A in patients with chronic rhinosinusitis with nasal polyps. / Takabayashi, Tetsuji; Kato, Atsushi; Peters, Anju T.; Hulse, Kathryn E.; Suh, Lydia A.; Carter, Roderick; Norton, James; Grammer, Leslie C.; Tan, Bruce K.; Chandra, Rakesh K.; Conley, David B.; Kern, Robert C.; Fujieda, Shigeharu; Schleimer, Robert P.

In: Journal of Allergy and Clinical Immunology, Vol. 132, No. 3, 01.01.2013.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Increased expression of factor XIII-A in patients with chronic rhinosinusitis with nasal polyps

AU - Takabayashi, Tetsuji

AU - Kato, Atsushi

AU - Peters, Anju T.

AU - Hulse, Kathryn E.

AU - Suh, Lydia A.

AU - Carter, Roderick

AU - Norton, James

AU - Grammer, Leslie C.

AU - Tan, Bruce K.

AU - Chandra, Rakesh K.

AU - Conley, David B.

AU - Kern, Robert C.

AU - Fujieda, Shigeharu

AU - Schleimer, Robert P.

PY - 2013/1/1

Y1 - 2013/1/1

N2 - 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. Conclusion: 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.

AB - 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. Conclusion: 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.

KW - Chronic rhinosinusitis

KW - M2 macrophages

KW - coagulation cascade

KW - factor XIII-A (FXIII-A)

KW - fibrin

KW - nasal polyps

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