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 journalArticlepeer-review

106 Scopus citations

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)
Pages (from-to)584-592.e4
JournalJournal of Allergy and Clinical Immunology
Volume132
Issue number3
DOIs
StatePublished - Sep 2013

Funding

Supported by National Institutes of Health grants R37HL068546-27 , R01HL078860 , and RO1AI072570 and the Ernest S. Bazley Trust . Disclosure of potential conflict of interest: A. Kato and B.K. Tan have received grants from the National Institutes of Health (NIH) . A. T. Peters has received payments for lectures from Baxter . L. C. Grammer has received a grant and travel support from the NIH ; has received a Bazley Foundation grant; has consultant arrangements with Astellas Pharmaceuticals; is employed by Northwestern University and Northwestern Medical Faculty Foundation; has received grants from the NIH , the Food Allergy Network, and S&C Electric ; has received payment for lectures from the American Academy of Allergy, Asthma & Immunology ; and has received royalties from Lippincott, UpToDate, BMJ, and Elsevier . R. P. Schleimer has received grants from the NIH and has consultant arrangements with Intersect ENT, GlaxoSmithKline, Allakos, and Aurasense. The rest of the authors declare that they have no relevant conflicts of interest.

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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