Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Oct;61(4):544-546.
doi: 10.1165/rcmb.2019-0138LE.

Muc5b Enhances Murine Honeycomb-like Cyst Formation

Jonathan S Kurche  1 , Evgenia Dobrinskikh  1 , Corinne E Hennessy  1 , Jonathan Huber  1 , Alani Estrella  1 , Laura A Hancock  1 , Marvin I Schwarz  1 , Tsukasa Okamoto  2 , Carlyne D Cool  1 , Ivana V Yang  1 , Christopher M Evans  1 , David A Schwartz  1
Affiliations

Muc5b Enhances Murine Honeycomb-like Cyst Formation

Jonathan S Kurche et al. Am J Respir Cell Mol Biol. 2019 Oct.
No abstract available

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Wild-type mice develop Muc5b-filled honeycomb cysts (HCs) in response to lung injury. Antibodies used for immunohistochemistry included goat anti-mouse Muc5b (11765, 1:1000; Everest), rabbit anti-mouse pro-SPC (ab90716, 1:100; Abcam), and chicken anti-mouse Krt5 (Poly9059, 1:1000; BioLegend). Appropriate fluorescent secondary antibodies were obtained from Jackson ImmunoResearch, reconstituted at 1 mg/ml, and used at 1:200. (A) Muc5b protein is increased in response to productive influenza infection (28 d postinfection) or repeated bleomycin treatment (*P < 0.05 and ***P < 0.005). (B) Influenza A H1N1 (H1N1) infection does not lead to significant fibrosis compared with UV-irradiated control virus as measured by hydroxyproline, whereas repeated bleomycin injury leads to significant increases in hydroxyproline compared with saline-treated control (***P < 0.005). (C) H1N1 generates considerable airspace remodeling resembling honeycombing (Krt5 stained DAB) 75 days after infection (top left). Similar to what is observed in humans, H1N1 HCs are characterized by Krt5-basal cells surrounding dense mucociliary structures filled with Muc5b+ colloid and generally exclude type II pneumocytes (top right). HCs also develop in mice subjected to repeated bleomycin injury (bottom left). Repeat bleomycin injury–derived HCs are generally indistinguishable from H1N1-derived HCs (bottom right). Honeycomb structures are highlighted by red (DAB panels) and white (IF panels) asterisks. (D) Cysts in mice subjected to single-dose bleomycin persist in the absence of significant fibrosis. (E) In general, resolution of H1N1 injury involves more robust honeycombing than repeat or single-dose bleomycin.
Figure 2.
Figure 2.
Durable murine honeycombing varies with expression of Muc5b in the bleomycin, but not H1N1, models. HC were morphometrically quantified via unbiased stereology; initially a 350 micron grid was used to quantify the volume fraction of the cysts. Cystic areas were then randomly sampled using a 100 micron grid to determine cyst size. Lung volume was calculated using the Cavalieri method. (A) No significant differences were observed in cyst volume or number based on genotype among mice infected with H1N1. (B) Bleomycin-injured mice expressing Muc5b under control of the SPC promoter had a significant increase in cyst volume (P < 0.05). The overall number of cysts is independent of genotype (*P < 0.05, **P < 0.01, and ***P < 0.005). KO = knockout; WT = wild-type (see text for additional strain details).
See this image and copyright information in PMC

References

    1. Raghu G, Chen SY, Yeh WS, Maroni B, Li Q, Lee YC, et al. Idiopathic pulmonary fibrosis in US Medicare beneficiaries aged 65 years and older: incidence, prevalence, and survival, 2001-11. Lancet Respir Med. 2014;2:566–572. - PubMed
    1. Fingerlin TE, Murphy E, Zhang W, Peljto AL, Brown KK, Steele MP, et al. Genome-wide association study identifies multiple susceptibility loci for pulmonary fibrosis. Nat Genet. 2013;45:613–620. - PMC - PubMed
    1. Nakano Y, Yang IV, Walts AD, Watson AM, Helling BA, Fletcher AA, et al. Muc5b promoter variant rs35705950 affects muc5b expression in the distal airways in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2016;193:464–466. - PMC - PubMed
    1. Yang IV, Coldren CD, Leach SM, Seibold MA, Murphy E, Lin J, et al. Expression of cilium-associated genes defines novel molecular subtypes of idiopathic pulmonary fibrosis. Thorax. 2013;68:1114–1121. - PMC - PubMed
    1. Seibold MA, Smith RW, Urbanek C, Groshong SD, Cosgrove GP, Brown KK, et al. The idiopathic pulmonary fibrosis honeycomb cyst contains a mucocilary pseudostratified epithelium. PLoS One. 2013;8:e58658. - PMC - PubMed

Publication types

MeSH terms