The development of nasal polyp disease involves early nasal mucosal inflammation and remodelling

PLoS One. 2013 Dec 10;8(12):e82373. doi: 10.1371/journal.pone.0082373. eCollection 2013.

Abstract

Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by both a chronic inflammation and tissue remodelling; as indicated by extracellular matrix protein deposition, basement membrane thickening, goblet cell hyperplasia and subepithelial edema, with reduced vessels and glands. Although remodelling is generally considered to be consequence of persistent inflammation, the chronological order and relationship between inflammation and remodelling in polyp development is still not clear. The aim of our study was therefore to investigate the pathological features prevalent in the development of nasal polyps and to elucidate the chronological order and relationship between inflammation and remodelling, by comparing specific markers of inflammation and remodelling in early stage nasal polyps confined to the middle turbinate (refer to as middle turbinate CRSwNP) obtained from 5 CRSwNP patients with bilateral polyposis, mature ethmoidal polyps from 6 CRSwNP patients, and normal nasal mucosal tissue from 6 control subjects. Middle turbinate CRSwNP demonstrated significantly more severe epithelial loss compared to mature ethmoidal polyps and normal nasal mucosa. The epithelial cell junction molecules E-cadherin, ZO-1 and occludin were also expressed in significantly lower amounts in mature ethmoidal polyps compared to healthy mucosa. Middle turbinate CRSwNP were further characterized by significantly increased numbers of subepithelial eosinophils and M2 type macrophages, with a distinct lack of collagen and deposition of fibronectin in polyp part. In contrast, the turbinate area of the middle turbinate CRSwNP was characterized by an increase in TGF-β activated myofibroblasts expressing α-SMA and vimentin, an increase in the number of pSmad2 positive cells, as well as increased deposition of collagen. These findings suggest a complex network of processes in the formation of CRSwNP; including gross epithelial damage and repair reactions, eosinophil and macrophage cell infiltration, and tissue remodelling. Furthermore, remodelling appears to occur in parallel, rather than subsequent to inflammation.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers / metabolism
  • Cadherins / metabolism
  • Collagen / metabolism
  • Female
  • Humans
  • Inflammation / metabolism
  • Inflammation / pathology
  • Macrophages / metabolism
  • Macrophages / pathology
  • Male
  • Nasal Mucosa / metabolism*
  • Nasal Mucosa / pathology*
  • Nasal Polyps / metabolism*
  • Nasal Polyps / pathology*
  • Smad2 Protein / metabolism
  • Transforming Growth Factor beta / metabolism
  • Vimentin / metabolism
  • Zonula Occludens-1 Protein / metabolism

Substances

  • Biomarkers
  • Cadherins
  • SMAD2 protein, human
  • Smad2 Protein
  • TJP1 protein, human
  • Transforming Growth Factor beta
  • Vimentin
  • Zonula Occludens-1 Protein
  • Collagen

Grants and funding

This work was supported by grants to Claus Bachert from the Flemish Scientific Research Board, Nr. A12/5-HB-KH3 and G.0436.04, the Global Allergy and Asthma European Network and the Interuniversity Attraction Poles Programme–Belgian State–Belgian Science Policy, Nr. IAP P6/35, and from the European Commission’s Seventh Framework programme under grant agreement 260895 (PREDICTA) and by grants to SXL from the National Natural Science Foundation of China (grant NO. 81271058)and Ph.D. Programs Foundation of Ministry of Education of China (NO.20100181110024). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.