Th2 milieu facilitates excessive fibrin deposition in nasal polyp tissue
Published Online: March 29, 2013
Chronis rhinosinusitis (CRS) is one of the most common chronic diseases in adults in the United States. CRS is typically classified into 2 types: CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). Generally, the symptoms of CRSwNP are more severe and can persist despite medical treatment and surgical intervention. Intense edematous stroma or formation of pseudocyst filled with plasma proteins is a prominent characteristic of nasal polyps (NP). However, the mechanisms by which NP retain plasma proteins in the submucosa rather than allowing them to pass through the epithelial layer remain unclear.
In a study published recently in The Journal of Allergy & Clinical Immunology (JACI), Takabayashi and colleagues examined the expression of factor XIII-A (FXIII-A) in CRS. FXIIIA is a factor that cross links fibrin and is of interest in CRS based on a recent report from this same group that cross linked fibrin is accumulated within NP tissue. Sinonasal tissues were collected from patients with CRS and control subjects. They assayed mRNA for FXIII-A using real-time PCR and measured FXIII-A protein by means of ELISA, immunohistochemistry, and immunofluorescence.
The authors observed that FXIII-A mRNA levels were significantly increased in NP from patient with CRSwNP compared with uncinate tissue from patients with CRS or control subjects. Similarly, FXIII-A protein levels were increased in NP. Immunofluorescence analysis revealed 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 FXIII-A producing cells within NP.
The authors suggest that overproduction of FXIII-A by M2 macrophages might contribute to the excessive fibrin deposition, which in turn retains exuded plasma proteins and participates in tissue remodeling, intense edema or pseudocyst formation in submucosae of NP tissue. If this hypothesis is correct, strategies to reduce the activity of the coagulation cascade might have therapeutic value in the treatment of CRSwNP.
The Journal of Allergy and Clinical Immunology (JACI) is the official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.