Muc5b is mainly expressed and sialylated in the nasal olfactory epithelium whereas Muc5ac is exclusively expressed and fucosylated in the nasal respiratory epithelium

Objectives Several studies have reported that inducible nitric oxide synthase (iNOS) was expressed within the epithelial cell of the trachea in asthmic patients and asthmic model animals. However, neither appearance nor localization of iNOS in the nasal mucosa of allergic rhinitis has been examined. This research clarifies expression and the localization of iNOS in the nasal mucosa of allergic rhinitis by using the allergic model mice. Methods Allergic rhinitis was induced in male mice at 6 weeks of age using purified Japanese cedar pollen allergen (Cry j 1). Cry j 1 was injected 2 times into the abdomen (day 0 and 4) and administered intranasally for 7 consecutive days (day 9–15). On day 22, the expression and localization of iNOS in nasal mucosa of both allergic rhinitis model and control mice were examined by immunohistochemistry. Results In control mice, the expression of iNOS was localized in olfactory nerve, nasal gland beneath the respiratory epithelium and vascular endothelial cells. In allergic rhinitis group, the expression of iNOS was not only localized in olfactory nerve, nasal gland, and vascular endothelial cells, but also in olfactory epithelium and respiratory epithelium. Conclusions The expression of iNOS was increased in olfactory epithelium and respiratory epithelium of allergic rhinitis mice compared with controls.

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Evidence of SARS-CoV2 entry protein ACE2 in the human nose and olfactory bulb

10.1101/2020.07.15.204602 ◽

2020 ◽

Author(s):

M. Klingenstein ◽

S. Klingenstein ◽

P.H. Neckel ◽

A. F. Mack ◽

A. Wagner ◽

...

Keyword(s):

Olfactory Bulb ◽

Olfactory Epithelium ◽

Olfactory Receptor ◽

Respiratory Epithelium ◽

Olfactory Receptor Neurons ◽

Basal Cells ◽

Sustentacular Cells ◽

Glandular Cells ◽

Receptor Neurons ◽

Human Nose

ABSTRACTUsually, pandemic COVID-19 disease, caused by SARS-CoV2, presents with mild respiratory symptoms such as fever, cough but frequently also with anosmia and neurological symptom. Virus-cell fusion is mediated by Angiotensin-Converting Enzyme 2 (ACE2) and Transmembrane Serine Protease 2 (TMPRSS2) with their organ expression pattern determining viral tropism. Clinical presentation suggests rapid viral dissemination to central nervous system leading frequently to severe symptoms including viral meningitis. Here, we provide a comprehensive expression landscape of ACE2 and TMPRSS2 proteins across human, post-mortem nasal and olfactory tissue. Sagittal sections through the human nose complemented with immunolabelling of respective cell types represent different anatomically defined regions including olfactory epithelium, respiratory epithelium of the nasal conchae and the paranasal sinuses along with the hardly accessible human olfactory bulb. ACE2 can be detected in the olfactory epithelium, as well as in the respiratory epithelium of the nasal septum, the nasal conchae and the paranasal sinuses. ACE2 is located in the sustentacular cells and in the glandular cells in the olfactory epithelium, as well as in the basal cells, glandular cells and epithelial cells of the respiratory epithelium. Intriguingly, ACE2 is not expressed in mature or immature olfactory receptor neurons and basal cells in the olfactory epithelium. Similarly ACE2 is not localized in the olfactory receptor neurons albeit the olfactory bulb is positive. Vice versa, TMPRSS2 can also be detected in the sustentacular cells and the glandular cells of the olfactory epithelium.Our findings provide the basic anatomical evidence for the expression of ACE2 and TMPRSS2 in the human nose, olfactory epithelium and olfactory bulb. Thus, they are substantial for future studies that aim to elucidate the symptom of SARS-CoV2 induced anosmia of via the olfactory pathway.

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A Subset of Olfactory Sensory Neurons Express Forkhead Box J1-Driven eGFP

Chemical Senses ◽

10.1093/chemse/bjz060 ◽

2019 ◽

Vol 44 (9) ◽

pp. 663-671 ◽

Cited By ~ 1

Author(s):

Eric D Larson ◽

Shivani Pathak ◽

Vijay R Ramakrishnan ◽

Thomas E Finger

Keyword(s):

Olfactory Bulb ◽

Sensory Neurons ◽

Olfactory Epithelium ◽

Respiratory Epithelium ◽

Egfp Expression ◽

Olfactory Sensory Neurons ◽

Receptor Cells ◽

Forkhead Box ◽

Motile Cilia ◽

Vomeronasal Sensory Neurons

Abstract Forkhead box protein J1 (FOXJ1), a member of the forkhead family transcription factors, is a transcriptional regulator of motile ciliogenesis. The nasal respiratory epithelium, but not olfactory epithelium, is lined with FOXJ1-expressing multiciliated epithelial cells with motile cilia. In a transgenic mouse where an enhanced green fluorescent protein (eGFP) transgene is driven by the human FOXJ1 promoter, robust eGFP expression is observed not only in the multiciliated cells of the respiratory epithelium but in a distinctive small subset of olfactory sensory neurons in the olfactory epithelium. These eGFP-positive cells lie at the extreme apical part of the neuronal layer and are most numerous in dorsal-medial regions of olfactory epithelium. Interestingly, we observed a corresponding small number of glomeruli in the olfactory bulb wherein eGFP-labeled axons terminate, suggesting that the population of eGFP+ receptor cells expresses a limited number of olfactory receptors. Similarly, a subset of vomeronasal sensory neurons expresses eGFP and is distributed throughout the full height of the vomeronasal sensory epithelium. In keeping with this broad distribution of labeled vomeronasal receptor cells, eGFP-labeled axons terminate in many glomeruli in both anterior and posterior portions of the accessory olfactory bulb. These findings suggest that Foxj1-driven eGFP marks a specific population of olfactory and vomeronasal sensory neurons, although neither receptor cell population possess motile cilia.

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A Subset of Olfactory Sensory Neurons Express Forkhead Box J1-Driven eGFP

10.1101/643460 ◽

2019 ◽

Author(s):

Shivani Pathak ◽

Eric D. Larson ◽

Vijay R. Ramakrishnan ◽

Thomas E Finger

Keyword(s):

Olfactory Bulb ◽

Sensory Neurons ◽

Olfactory Epithelium ◽

Respiratory Epithelium ◽

Egfp Expression ◽

Olfactory Sensory Neurons ◽

Receptor Cells ◽

Forkhead Box ◽

Motile Cilia ◽

Vomeronasal Sensory Neurons

AbstractForkhead box protein J1 (Foxj1), a member of the forkhead family transcription factors, is a transcriptional regulator of motile ciliogenesis. The nasal respiratory epithelium, but not olfactory epithelium, is lined with FOXJ1-expressing multiciliated epithelial cells with motile cilia. Using a Foxj1-eGFP reporter mouse, we find robust eGFP expression not only in the multi-ciliated cells of the respiratory epithelium, but in a distinctive small subset of olfactory sensory neurons in the olfactory epithelium. These eGFP-positive cells lie at the extreme apical part of the neuronal layer and are most numerous in dorsal-medial regions of olfactory epithelium. Interestingly, we observed a corresponding small number of glomeruli in the olfactory bulb wherein eGFP-labeled axons terminate, suggesting that the population of eGFP+ receptor cells expresses a limited number of olfactory receptors. Similarly, a subset of vomeronasal sensory neurons express eGFP but these distribute throughout the full height of the vomeronasal sensory epithelium. In keeping with this broad distribution of labeled vomeronasal receptor cells, eGFP labeled axons terminate in many glomeruli of the accessory olfactory bulb. These findings suggest that Foxj1-driven eGFP marks a specific population of olfactory and vomeronasal sensory neurons although neither receptor cell population possess motile cilia.

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3-Methylindole-Induced Nasal Mucosal Damage in Mice

Veterinary Pathology ◽

10.1177/030098588702400506 ◽

1987 ◽

Vol 24 (5) ◽

pp. 400-403 ◽

Cited By ~ 29

Author(s):

M. A. M. Turk ◽

W. G. Henk ◽

W. Flory

Keyword(s):

Olfactory Epithelium ◽

Intraperitoneal Injection ◽

Squamous Metaplasia ◽

Mucosal Damage ◽

Respiratory Epithelium ◽

Osseous Tissue ◽

Epithelial Hyperplasia ◽

Cellular Swelling

3-Methylindole (3MI) damages nasal olfactory epithelium in mice. Lesions were studied histologically from 30 minutes to 28 days after intraperitoneal injection of 400 mg 3MI/kg. Cellular swelling was apparent in olfactory epithelium by 6 hours after injection of 3MI, while respiratory epithelium was normal. Necrosis of olfactory epithelium and subepithelial glands was diffuse by 48 hours. Subsequent ulceration resulted in epithelial hyperplasia, squamous metaplasia, fibroplasia, and ossification. Partially occlusive intranasal fibrous and osseous tissue persisted through 28 days after 3MI injection.

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Differential Expression of Mucins in Murine Olfactory Versus Respiratory Epithelium

10.1101/620757 ◽

2019 ◽

Cited By ~ 1

Author(s):

Christopher Kennel ◽

Elizabeth A. Gould ◽

Eric D. Larson ◽

Ernesto Salcedo ◽

Thad W. Vickery ◽

...

Keyword(s):

Differential Expression ◽

Olfactory Epithelium ◽

Respiratory Epithelium ◽

Mucin 1 ◽

Clinical Observations ◽

Respiratory Epithelia ◽

Mucin Expression ◽

Mucus Rheology ◽

Mucin 2 ◽

Final Manuscript

AbstractMucins are a key component of the airway surface liquid and serve many functions. Given the numerous differences in olfactory versus respiratory nasal epithelia, we hypothesized that mucins would be differentially expressed between these two areas. Secondarily, we evaluated for changes in mucin expression with radiation exposure, given the clinical observations of nasal dryness, altered mucus rheology, and smell loss in radiated patients. Immunofluorescence staining was performed in a mouse model to determine the expression of mucins 1, 2, 5AC and 5B in nasal respiratory and olfactory epithelia of control mice and one week after exposure to 8 gy of radiation. Mucins 1, 5AC and 5B exhibited differential expression between olfactory and respiratory epithelium while mucin 2 showed no difference. Within the olfactory epithelium, mucin 1 was located in a lattice-like pattern around gaps corresponding to dendritic knobs of olfactory sensory neurons, whereas in respiratory epithelium it was only intermittently expressed. Mucin 5AC was expressed by subepithelial glands in both epithelial types but to a higher degree in the olfactory epithelium. Mucin 5B was expressed by submucosal glands in the olfactory epithelium but by surface epithelial cells in respiratory epithelium. At one-week after exposure to single-dose 8 gy of radiation, no qualitative effects were seen on mucin expression. Our findings demonstrate that murine olfactory and respiratory epithelia express mucins differently, and characteristic patterns of mucins 1, 5AC, and 5B can be used to define the underlying epithelium. Radiation (8 gy) does not appear to affect mucin expression at one week.Author RolesChristopher Kennel conceived, organized and executed the study, performed the analysis, and contributed to the manuscript.Elizabeth Gould conceived and executed the study, and contributed to the manuscript.Diego Restrepo conceived and executed the study, supervised the experiments, reviewed the analysis, and contributed to the manuscript.Ernesto Salcedo performed experiments and reviewed the manuscript.Thad Vickery performed experiments and reviewed the manuscript.Eric Larson performed experiments and reviewed the manuscript.Vijay Ramakrishnan conceived and executed the study, reviewed the analysis, and contributed to the manuscript.All authors discussed the results and implications and contributed to the final manuscript.

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Evidence of SARS-CoV2 Entry Protein ACE2 in the Human Nose and Olfactory Bulb

Cells Tissues Organs ◽

10.1159/000513040 ◽

2021 ◽

pp. 1-10

Author(s):

Moritz Klingenstein ◽

Stefanie Klingenstein ◽

Peter H. Neckel ◽

Andreas F. Mack ◽

Andreas P. Wagner ◽

...

Keyword(s):

Olfactory Bulb ◽

Olfactory Epithelium ◽

Olfactory Receptor ◽

Respiratory Epithelium ◽

Olfactory Receptor Neurons ◽

Basal Cells ◽

Sustentacular Cells ◽

Glandular Cells ◽

Receptor Neurons ◽

Human Nose

Usually, pandemic COVID-19 disease, caused by SARS-CoV2, presents with mild respiratory symptoms such as fever, cough, but frequently also with anosmia and neurological symptoms. Virus-cell fusion is mediated by angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) with their organ expression pattern determining viral tropism. Clinical presentation suggests rapid viral dissemination to the central nervous system leading frequently to severe symptoms including viral meningitis. Here, we provide a comprehensive expression landscape of ACE2 and TMPRSS2 proteins across human postmortem nasal and olfactory tissue. Sagittal sections through the human nose complemented with immunolabelling of respective cell types represent different anatomically defined regions including olfactory epithelium, respiratory epithelium of the nasal conchae and the paranasal sinuses along with the hardly accessible human olfactory bulb. ACE2 can be detected in the olfactory epithelium as well as in the respiratory epithelium of the nasal septum, the nasal conchae, and the paranasal sinuses. ACE2 is located in the sustentacular cells and in the glandular cells in the olfactory epithelium as well as in the basal cells, glandular cells, and epithelial cells of the respiratory epithelium. Intriguingly, ACE2 is not expressed in mature or immature olfactory receptor neurons and basal cells in the olfactory epithelium. Similarly, ACE2 is not localized in the olfactory receptor neurons albeit the olfactory bulb is positive. Vice versa, TMPRSS2 can also be detected in the sustentacular cells and the glandular cells of the olfactory epithelium. Our findings provide the basic anatomical evidence for the expression of ACE2 and TMPRSS2 in the human nose, olfactory epithelium, and olfactory bulb. Thus, they are substantial for future studies that aim to elucidate the symptom of SARS-CoV2 induced anosmia via the olfactory pathway.

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Dexamethasone Effect on Embryonic Chick Respiratory Epithelium

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100053905 ◽

1982 ◽

Vol 40 ◽

pp. 248-249

Author(s):

M.R. Richter ◽

R.V. Blystone

Keyword(s):

Lung Development ◽

Critical Role ◽

Respiratory Epithelium ◽

Chick Embryos ◽

Embryonic Chick ◽

White Leghorn ◽

Lung Maturation ◽

Synthetic Analogs ◽

Lung Physiology ◽

Avian Lung

Dexamethasone and other synthetic analogs of corticosteroids have been employed clinically as enhancers of lung development. The mechanism(s) by which this steroid induction of later lung maturation operates is not clear. This study reports the effect on lung epithelia of dexamethasone administered at different intervals during development. White Leghorn chick embryos were used so as to remove possible maternal and placental influences on the exogenously applied steroid. Avian lung architecture does vary from mammals; however, respiratory surfactant produced by the lung epithelia serves an equally critical role in avian lung physiology.

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Bronchial stereocilia in the immotile cilia syndrome: A case report

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100110635 ◽

1984 ◽

Vol 42 ◽

pp. 52-53

Author(s):

George Price ◽

Lizardo Cerezo

Keyword(s):

Surface Modifications ◽

Respiratory Epithelium ◽

Immotile Cilia ◽

Kartagener's Syndrome ◽

Membrane Blebs ◽

Radial Spokes ◽

Males And Females ◽

Dynein Arms ◽

Ultrastructural Finding ◽

Ultrastructural Findings

Ultrastructural defects of ciliary structure have been known to cause recurrent sino-respiratory infection concurrent with Kartagener's syndrome. (1,2,3) These defects are also known to cause infertility in both males and females. (4) Overall, the defects are defined as the Immotile, or Dyskinetic Cilia Syndrome (DCS). Several ultrastructural findings have been described, including decreased number of cilia, multidirection orientation, fused and compound cilia, membrane blebs, excess matrix in the axoneme, missing outer tubular doublets, translocated doublets, defective radial spokes and dynein arms. A rare but noteworthy ultrastructural finding in DCS is the predominance of microvilli-like structures on the luminal surface of the respiratory epithelium. (5,6) These permanent surface modifications of the apical respiratory epithelium no longer resemble cilia but reflect the ultrastructure of stereocilia, similar to that found in the epidydimal epithelium. Like microvilli, stereocilia are devoid of microtubular ultrastructure in comparison with true cilia.

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Methods for making stereoslides and -prints, with freeze-etched olfactory epithelium as example

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100113408 ◽

1984 ◽

Vol 42 ◽

pp. 704-705

Author(s):

Bert Ph. M. Menco ◽

Ido F. Menco ◽

Frans L.T. Verdonk

Keyword(s):

Electron Microscope ◽

Olfactory Epithelium ◽

Three Dimensional ◽

Supporting Cell ◽

Structural Features ◽

Extensive Study ◽

Sprague Dawley ◽

Freezing Method ◽

Respiratory Epithelia ◽

Three Dimensional Presentation

Previously we presented an extensive study of the distributions of intramembranous particles of structures in apical surfaces of nasal olfactory and respiratory epithelia of the Sprague-Dawley rat. For the same structures these distributions were compared in samples which were i) chemically fixed and cryo-protected with glycerol before cryo-fixation, after excision, and ii)ultra-rapidly frozen by means of the slam-freezing method. Since a three-dimensional presentation markedly improves visualization of structural features micrographs were presented as stereopairs. Two exposures were made by tiling the sample stage of the electron microscope 6° in either direction with an eucentric goniometer. The negatives (Agfa Pan 25 Professional) were reversed with Kodak Technical Pan Film 2415 developed in D76 1:1. The prints were made from these reversed negatives. As an example tight-junctional features of an olfactory supporting cell in a region where this cell conjoined with two other cells are presented (Fig. 1).

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