The Idiopathic Pulmonary Fibrosis Honeycomb Cyst Contains A Mucocilary Pseudostratified Epithelium

Max A Seibold,Steve D Groshong,Marvin I Schwarz,Gregory P Cosgrove,Cydney Urbanek,Kevin K Brown,David A Schwartz,Susan D Reynolds,Russell W Smith,Mauricio Rojas

doi:10.1371/journal.pone.0058658

Max A Seibold, Steve D Groshong + Show 8 more

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https://doi.org/10.1371/journal.pone.0058658

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Journal: PloS one	Publication Date: Mar 20, 2013
Citations: 218	License type: CC BY 4.0

Affiliation: University of Colorado Denver, National Jewish Health

Abstract

BackgroundWe 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.MethodsImmunofluorescence 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).ResultsMUC5B-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.ConclusionsThe 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.

Highlights

Alveolar scaring is a pathological hallmark of Idiopathic Pulmonary Fibrosis/Usual Interstitial Pneumonia (IPF/UIP) and this histological change parallels the disease-associated decrease in lung function
This risk allele was associated with increased mucin 5B (MUC5B) expression in unaffected subjects and mRNA levels were 37-fold greater in those who were homozygous for the polymorphism [8]
Study Population De-identified formalin-fixed paraffin-embedded lower lobe lung tissue and data from 22 subjects with a diagnosis of IPF/UIP were obtained from the Lung Tissue Research Consortium (LTRC) which is supported by the National Heart, Lung, and Blood Institute (NHLBI) (Table 1)

Summary

Introduction

Alveolar scaring is a pathological hallmark of Idiopathic Pulmonary Fibrosis/Usual Interstitial Pneumonia (IPF/UIP) and this histological change parallels the disease-associated decrease in lung function. We identified a common polymorphism in the mucin 5B (MUC5B) promoter that was associated with a markedly increased risk of developing both familial and sporadic IPF/UIP [8,9]. This risk allele was associated with increased MUC5B expression in unaffected subjects and mRNA levels were 37-fold greater in those who were homozygous for the polymorphism [8]. 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

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Conclusion