4.5 Article

Mucus composition abnormalities in sinonasal mucosa of chronic rhinosinusitis with and without nasal polyps

Journal

INFLAMMATION
Volume 44, Issue 5, Pages 1937-1948

Publisher

SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s10753-021-01471-6

Keywords

mucus; lysozyme; mucins; hypoxia-inducible factor; chronic rhinosinusitis

Funding

  1. National Medical Research Council, Singapore [NMRC/CIRG/1458/2016]
  2. Major Research Development Program of Shandong Province [2016GSF201084]
  3. National Nature Science Foundation of China [81873692]
  4. European Allergy and Clinical Immunology (EAACI) Research Fellowship 2019

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The study found differences in nasal mucus composition between healthy individuals and chronic rhinosinusitis patients, which may contribute to the pathology of chronic nasal diseases, mainly reflected in glandular hyperplasia and goblet cell hyperplasia.
Mucus secretion and its composition are vital in the maintenance of airway health, among which hypoxia-inducible factors (HIFs) are thought to be involved in the regulation of mucin synthesis and regulation. Nasal mucus composition difference between healthy individuals and chronic rhinosinusitis (CRS) patients may contribute to the pathology of chronic nasal diseases, but so far, their role has yet to be completely understood. Nasal biopsy specimens were obtained from 24 healthy subjects and 99 patients with CRS without (CRSsNP, n=36) or with (CRSwNP, n=63) nasal polyps. Immunohistochemical (IHC) and immunofluorescent (IF) staining, quantitative real-time PCR, and western blot were performed to compare the nasal mucus composition between the subjects. Areas of the serous gland and mucous gland were both significantly increased in CRSsNP patients. In CRSwNP patients, a decrease in submucosal gland density and a marked increase in goblet cells were observed. The major gel-forming mucins in the sinonasal mucosa of CRSsNP and CRSwNP are MUC5B and MUC5AC respectively. Mucous cells are found in a higher proportion in both CRSsNP and CRSwNP. The proportion of MUC5AC-positive goblet cells was increased in CRSwNP. The mRNA level of HIF-2 alpha was significantly increased in CRS, and both HIF-1 alpha and HIF-2 alpha were expressed in serous cell but not mucous cell. Over secretion and altered composition of mucus are observed in sinonasal mucosa of CRS, which was mainly associated with glandular hyperplasia in CRSsNP and goblet cell hyperplasia in CRSwNP. Mucus abnormality compromised both non-specific and specific antimicrobial capabilities in the sinonasal mucosa. HIF expression may contribute to differences in mucin synthesis and serous gland regulation, which needs further investigation to understand the pathology of CRS.

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