Gel-forming mucins form distinct morphologic structures in airways

Lynda S. Ostedgaard, Thomas O. Moninger, James D. McMenimen, Nicholas M. Sawin, Connor P. Parker, Ian M. Thornell, Linda S. Powers, Nicholas D. Gansemer, Drake C. Bouzek, Daniel P. Cook, David K. Meyerholz, Mahmoud H.Abou Alaiwa, David A. Stoltz, Michael J. Welsh

Research output: Contribution to journalArticlepeer-review

88 Scopus citations

Abstract

Gel-forming mucins, the primary macromolecular components of airway mucus, facilitate airway clearance by mucociliary transport. In cystic fibrosis (CF) altered mucus properties impair mucociliary transport. Airways primarily secrete two closely related gel-forming mucins, MUC5B and MUC5AC. However, their morphologic structures and associations in airways that contain abundant submucosal glands and goblet cells are uncertain. Moreover, there is limited knowledge about mucins in airways not affected by inflammation, infection, or remodeling or in CF airways. Therefore, we examined airways freshly excised from newborn non-CF pigs and CF pigs before secondary manifestations develop. We found that porcine submucosal glands produce MUC5B, whereas goblet cells produce predominantly MUC5AC plus some MUC5B. We found that MUC5B emerged from submucosal gland ducts in the form of strands composed of multiple MUC5B filaments. In contrast, MUC5AC emerged from goblet cells as wispy threads and sometimes formed mucin sheets. In addition, MUC5AC often partially coated the MUC5B strands. Compared with non-CF, MUC5B more often filled CF submucosal gland ducts. MUC5AC sheets also accumulated in CF airways overlying MUC5B strands. These results reveal distinct morphology and interactions for MUC5B and MUC5AC and suggest that the two mucins make distinct contributions to mucociliary transport. Thus, they provide a framework for understanding abnormalities in disease.

Original languageEnglish
Pages (from-to)6842-6847
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume114
Issue number26
DOIs
StatePublished - Jun 27 2017

Keywords

  • Asthma
  • COPD
  • Cystic fibrosis
  • Lung
  • Mucus

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