title: The idiopathic pulmonary fibrosis honeycomb cyst contains a mucocilary pseudostratified epithelium.
abstract: BACKGROUND
  We previously identified a MUC5B gene promoter-variant that is a risk allele for sporadic and familial Idiopathic Pulmonary Fibrosis/Usual Interstitial Pneumonia (IPF/UIP). This allele was strongly associated with increased MUC5B gene expression in lung tissue from unaffected subjects. Despite the strong association of this airway epithelial marker with disease, little is known of mucin expressing structures or of airway involvement in IPF/UIP.
  
  
  METHODS
  Immunofluorescence was used to subtype mucus cells according to MUC5B and MUC5AC expression and to identify ciliated, basal, and alveolar type II (ATII) cells in tissue sections from control and IPF/UIP subjects. Staining patterns were quantified for distal airways (Control and IPF/UIP) and in honeycomb cysts (HC).
  
  
  RESULTS
  MUC5B-expressing cells (EC) were detected in the majority of control distal airways. MUC5AC-EC were identified in half of these airways and only in airways that contained MUC5B-EC. The frequency of MUC5B+ and MUC5AC+ distal airways was increased in IPF/UIP subjects. MUC5B-EC were the dominant mucus cell type in the HC epithelium. The distal airway epithelium from control and IPF/UIP subjects and HC was populated by basal and ciliated cells. Most honeycombing regions were distinct from ATII hyperplasic regions. ATII cells were undetectable in the overwhelming majority of HC.
  
  
  CONCLUSIONS
  The distal airway contains a pseudostratified mucocilary epithelium that is defined by basal epithelial cells and mucus cells that express MUC5B predominantly. These data suggest that the HC is derived from the distal airway.
authors.affiliation: Center for Genes, Environment and Health, National Jewish Health, Denver, Colorado, United States of America.
authors.forename: Max A
authors.initials: MA
authors.lastname: Seibold
authors.forename: Russell W
authors.initials: RW
authors.lastname: Smith
authors.forename: Cydney
authors.initials: C
authors.lastname: Urbanek
authors.forename: Steve D
authors.initials: SD
authors.lastname: Groshong
authors.forename: Gregory P
authors.initials: GP
authors.lastname: Cosgrove
authors.forename: Kevin K
authors.initials: KK
authors.lastname: Brown
authors.forename: Marvin I
authors.initials: MI
authors.lastname: Schwarz
authors.forename: David A
authors.initials: DA
authors.lastname: Schwartz
authors.forename: Susan D
authors.initials: SD
authors.lastname: Reynolds
mesh_terms: D000328:Adult; D056809:Alveolar Epithelial Cells / Q000473:pathology; D016022:Case-Control Studies; D003560:Cysts / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D055271:Mucin 5AC / Q000235:genetics / Q000378:metabolism*; D055257:Mucin-5B / Q000235:genetics / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation
chemical_list: C524678:MUC5AC protein, human; C524578:MUC5B protein, human; D055271:Mucin 5AC; D055257:Mucin-5B