The Development of Nasal Polyp Disease Involves Early Nasal Mucosal Inflammation and Remodelling

• Published in: PloS one Vol. 8; no. 12; p. e82373
• Main Authors: Meng, Juan, Zhou, Peng, Liu, Yafeng, Liu, Feng, Yi, Xuelian, Liu, Shixi, Holtappels, Gabriele, Bachert, Claus, Zhang, Nan
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 10.12.2013; Public Library of Science (PLoS)
• Subjects: Adult; Asthma; Biomarkers - metabolism; Bone; Bone morphogenetic proteins; Cadherins - metabolism; Collagen; Collagen - metabolism; Deposition; Disease; E-cadherin; Edema; Eosinophils; Epithelial cells; Extracellular matrix; Female; Fibroblasts; Fibronectin; Fibronectins; Gene expression; Glands; Hospitals; Humans; Hyperplasia; Infiltration; Inflammation; Inflammation - metabolism; Inflammation - pathology; Laboratories; Leukocytes (eosinophilic); Macrophages; Macrophages - metabolism; Macrophages - pathology; Male; Matrix protein; Medical schools; Membrane proteins; Mucosa; Nasal Mucosa - metabolism; Nasal Mucosa - pathology; Nasal Polyps - metabolism; Nasal Polyps - pathology; Nose; Otolaryngology; Patients; Polyposis; Polyps; Rhinosinusitis; Smad2 Protein - metabolism; Studies; Thickening; Transforming Growth Factor beta - metabolism; Transforming growth factors; Vimentin; Vimentin - metabolism; White people; Zonula occludens-1 protein; Zonula Occludens-1 Protein - metabolism; Belgium
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0082373

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.