Journal article
Gel-forming mucins form distinct morphologic structures in airways
Proceedings of the National Academy of Sciences - PNAS, Vol.114(26), pp.6842-6847
06/27/2017
DOI: 10.1073/pnas.1703228114
PMCID: PMC5495256
PMID: 28607090
Abstract
Mucus propelled by cilia is key for removing particulates from lungs by mucociliary transport. The major structural components of airway mucus are two gel-forming mucins, MUC5B and MUC5AC. These mucins exhibit distinct morphologic structures. MUC5B is secreted by submucosal glands in the form of strands. MUC5AC is secreted by goblet cells as threads and thin sheets. After emerging onto the airway surface, the two mucins associate to form MUC5B strands partially covered with MUC5AC. These distinct morphologic structures likely enable efficient mucociliary transport. In cystic fibrosis, strands become entangled, MUC5B often fills submucosal gland ducts, and MUC5AC sheets are larger, are more abundant, and overlie strands. Disrupted anion secretion in cystic fibrosis alters mucin morphology, which will impair mucociliary transport.
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.
Details
- Title: Subtitle
- Gel-forming mucins form distinct morphologic structures in airways
- Creators
- Lynda S Ostedgaard - Department of Internal Medicine, Pappajohn Biomedical Institute, Roy J. and Lucille A. Carver College of MedicineThomas O Moninger - Department of Internal Medicine, Pappajohn Biomedical Institute, Roy J. and Lucille A. Carver College of MedicineJames D McMenimen - Department of Internal Medicine, Pappajohn Biomedical Institute, Roy J. and Lucille A. Carver College of MedicineNicholas M Sawin - Department of Internal Medicine, Pappajohn Biomedical Institute, Roy J. and Lucille A. Carver College of MedicineConnor P Parker - Department of Internal Medicine, Pappajohn Biomedical Institute, Roy J. and Lucille A. Carver College of MedicineIan M Thornell - Department of Internal Medicine, Pappajohn Biomedical Institute, Roy J. and Lucille A. Carver College of MedicineLinda S Powers - Department of Internal Medicine, Pappajohn Biomedical Institute, Roy J. and Lucille A. Carver College of MedicineNicholas D Gansemer - Department of Internal Medicine, Pappajohn Biomedical Institute, Roy J. and Lucille A. Carver College of MedicineDrake C Bouzek - Department of Internal Medicine, Pappajohn Biomedical Institute, Roy J. and Lucille A. Carver College of MedicineDaniel P Cook - Department of Internal Medicine, Pappajohn Biomedical Institute, Roy J. and Lucille A. Carver College of MedicineDavid K Meyerholz - Department of Pathology, Roy J. and Lucille A. Carver College of MedicineMahmoud H Abou Alaiwa - Department of Internal Medicine, Pappajohn Biomedical Institute, Roy J. and Lucille A. Carver College of MedicineDavid A Stoltz - Department of Internal Medicine, Pappajohn Biomedical Institute, Roy J. and Lucille A. Carver College of MedicineMichael J Welsh - Department of Internal Medicine, Pappajohn Biomedical Institute, Roy J. and Lucille A. Carver College of Medicine
- Resource Type
- Journal article
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.114(26), pp.6842-6847
- DOI
- 10.1073/pnas.1703228114
- PMID
- 28607090
- PMCID
- PMC5495256
- NLM abbreviation
- Proc Natl Acad Sci U S A
- ISSN
- 0027-8424
- eISSN
- 1091-6490
- Publisher
- National Academy of Sciences
- Grant note
- HL91842 / HHS | National Institutes of Health (NIH) WELSH15R0 / Cystic Fibrosis Foundation (CFF) HL51670 / HHS | National Institutes of Health (NIH) HL117744 / HHS | National Institutes of Health (NIH)
- Alternative title
- Morphologic appearance of airway mucin
- Language
- English
- Date published
- 06/27/2017
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Neurology; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Stead Family Department of Pediatrics; Pathology; Anesthesia; Neurosurgery; Internal Medicine
- Record Identifier
- 9984025414102771
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