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.
journal_name
Proc Natl Acad Sci U S Aauthors
Ostedgaard LS,Moninger TO,McMenimen JD,Sawin NM,Parker CP,Thornell IM,Powers LS,Gansemer ND,Bouzek DC,Cook DP,Meyerholz DK,Abou Alaiwa MH,Stoltz DA,Welsh MJdoi
10.1073/pnas.1703228114subject
Has Abstractpub_date
2017-06-27 00:00:00pages
6842-6847issue
26eissn
0027-8424issn
1091-6490pii
1703228114journal_volume
114pub_type
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