scholarly journals Goblet Cell Hyperplasia Increases SARS-CoV-2 Infection in COPD

2020 ◽  
Author(s):  
Jaspreet K. Osan ◽  
Sattya N. Talukdar ◽  
Friederike Feldmann ◽  
Beth Ann DeMontigny ◽  
Kailey Jerome ◽  
...  

SummarySARS-CoV-2 has become a major problem across the globe, with approximately 50 million cases and more than 1 million deaths and currently no approved treatment or vaccine. Chronic obstructive pulmonary disease (COPD) is one of the underlying conditions in adults of any age that place them at risk for developing severe illness associated with COVID-19. We established an airway epithelium model to study SARS-CoV-2 infection in healthy and COPD lung cells. We found that both the entry receptor ACE2 and the co-factor transmembrane protease TMPRSS2 are expressed at higher levels on nonciliated goblet cell, a novel target for SARS-CoV-2 infection. We observed that SARS-CoV-2 infected goblet cells and induced syncytium formation and cell sloughing. We also found that SARS-CoV-2 replication was increased in the COPD airway epithelium likely due to COPD associated goblet cell hyperplasia. Our results reveal goblet cells play a critical role in SARS-CoV-2 infection in the lung.

2011 ◽  
Vol 224 (2) ◽  
pp. 203-211 ◽  
Author(s):  
Vasiliy V Polosukhin ◽  
Justin M Cates ◽  
William E Lawson ◽  
Aaron P Milstone ◽  
Anton G Matafonov ◽  
...  

2007 ◽  
Vol 117 (4) ◽  
pp. 978-988 ◽  
Author(s):  
Kwon-Sik Park ◽  
Thomas R. Korfhagen ◽  
Michael D. Bruno ◽  
Joseph A. Kitzmiller ◽  
Huajing Wan ◽  
...  

2005 ◽  
Vol 114 (12) ◽  
pp. 958-965 ◽  
Author(s):  
Maria T. Peña ◽  
Pawandeep K. Aujla ◽  
Kantilal M. Patel ◽  
George H. Zalzal ◽  
Mary C. Rose

Objectives: The purpose of this study was to analyze MUC5AC protein expression in sinus mucosal specimens of children with and without chronic sinusitis. Methods: Morphometric, histologic, and immunohistochemical analyses were carried out on sinus mucosa of 7 children with chronic sinusitis and 6 children without sinusitis. Results: MUC5AC protein was expressed in a subset of goblet cells in the surface epithelium, but not in the submucosal glands in either pediatric population. The number of goblet cells that expressed MUC5AC mucin was not significantly different in patients with and without chronic sinusitis. All specimens had similar numbers of goblet cells in the surface epithelium. Conclusions: The data demonstrate that neither goblet cell hyperplasia nor increased MUC5AC expression occurs in the sinus mucosa of children with chronic sinusitis. This suggests that in contrast to asthma, in which goblet cell hyperplasia is present in the lower respiratory tract, mucus hypersecretion in pediatric chronic sinusitis may involve other secretory cells, eg, submucosal glandular cells, and mucins secreted by these glandular cells.


2017 ◽  
Author(s):  
Joan Antoni Fernández-Blanco ◽  
Liisa Arike ◽  
Anna Ermund ◽  
Dalia Fakih ◽  
Ana M. Rodríguez-Piñeiro ◽  
...  

AbstractThe respiratory tract is normally kept essentially free of bacteria by cilia-mediated mucus transport, but in chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF) mucus accumulates due to goblet cell hyperplasia and mucin overexpression. To address mechanisms behind the mucus accumulation, the elastase-induced mouse model was utilized. The proteomes of bronchoalveolar lavage fluid from elastase-induced mice and COPD patients showed similarities to each other and to colonic mucus. Lung mucus showed a striated, laminated appearance in the elastase-induced mice, COPD and CF, resembling that observed for colonic mucus. Less mucus obstruction was observed in mice lacking the Muc5b mucin. The accumulated mucus plugs of the elastase-induced mice were possible to wash out, but a mucus layer covering the epithelium remained attached to the surface goblet cells also after hypertonic saline washings as widely used in CF therapy. The results suggest that the lung can convert its mucus system into an attached mucus layer that protects the epithelium, similarly to the colon.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Mohamad N. Ali ◽  
Michiko Mori ◽  
Tinne C. J. Mertens ◽  
Premkumar Siddhuraj ◽  
Jonas S. Erjefält ◽  
...  

Abstract Osteopontin (OPN) plays a role in inflammation via recruitment of neutrophils and tissue remodeling. In this study, we investigated the distribution of OPN-expressing cells in the airway epithelium of normal lung tissue and that from patients with chronic obstructive pulmonary disease (COPD). OPN was detected on the epithelial cell surface of small airways and in scattered cells within the epithelial cell layer. Staining revealed higher OPN concentrations in tissue showing moderate to severe COPD compared to that in controls. In addition, OPN expression was confined to goblet and club cells, and was absent from ciliated and basal cells as detected via immunohistochemistry. However, OPN expression was up-regulated in submerged basal cells cultures exposed to cigarette smoke (CS) extract. Cell fractioning of air-liquid interface cultures revealed increased OPN production from basal compartment cells compared to that in luminal fraction cells. Furthermore, both constitutive and CS-induced expression of OPN decreased during differentiation. In contrast, cultures stimulated with interleukin (IL)-13 to promote goblet cell hyperplasia showed increased OPN production in response to CS exposure. These results indicate that the cellular composition of the airway epithelium plays an important role in OPN expression and that these levels may reflect disease endotypes in COPD.


Author(s):  
Linsey E. Haswell ◽  
David Smart ◽  
Tomasz Jaunky ◽  
Andrew Baxter ◽  
Simone Santopietro ◽  
...  

1995 ◽  
Vol 311 (1) ◽  
pp. 293-297 ◽  
Author(s):  
M Tomita ◽  
H Itoh ◽  
N Ishikawa ◽  
A Higa ◽  
H Ide ◽  
...  

A cDNA encoding mouse intestinal trefoil factor (mITF) was successfully cloned and sequenced from the small intestine of C57BL/6 mouse by using the combination of reverse transcription-PCR and rapid amplification of cDNA ends methods. The gene was, similar to rat and human ITFs, mainly expressed in the small and large intestine. The mITF expression was up-regulated during the recovery phase after depletion of goblet cells in acetic acid-induced colitis. On the other hand, the expression in the jejunum was not altered, while goblet cell hyperplasia was induced by Nippostrongylus brasiliensis infection. These results suggest that the mITF expression did not simply correlate with the number of goblet cells. The mITF may play an important role in the maintenance and repair of mucosal function of the rectum. Additionally, the mITF in the jejunum may play a role in alteration of the physicochemical nature of goblet cell mucins, thereby affecting the establishment of intestinal helminths.


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