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Cell Contacts and Airway Epithelial Damage in Asthma
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
2005 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Airway epithelial damage is commonly found in asthma patients. Epithelial damage was investigated with special reference to contacts between epithelial cells.

Eosinophils, common in allergic asthma, secrete cationic proteins, particularly major basic protein (MBP). The effect of poly-L-arginine, an analogue of MBP, on airway epithelial cells was investigated. Poly-L-arginine induced membrane damage, resulting in increased permeability, loss of cell-cell contracts (tight junctions and desmosomes) and generalized cell damage.

Adhesion molecules on airway epithelial cells may be important in recruiting leukocytes. Interferon (IFN)-γ increased intracellular adhesion molecule-1 expression in airway epithelial cell lines. A combination of interleukin-4 and IFN-γ opened the tight junctions.

Epithelial damage in asthma was studied at the ultrastructural level in bronchial biopsies from patients with atopic or non-atopic asthma, and healthy controls. Epithelial damage was extensive in both asthma groups. In basal and columnar cells, relative desmosome length was reduced by 30-40%. In columnar cells, half-desmosomes were noticed. Changes tended to be more extensive in atopic asthma, but there was no significant difference between the two groups. Reduced desmosomal contact may be important in the epithelial shedding observed in asthma. The contact area between columnar cells and basal lamina is relatively small in the human airway. Attachment of columnar cells to the basal lamina occurs indirectly, via desmosomal attachment to basal cells. Direct attachment of columnar cells to the basal lamina is weakened in asthmatics.

Nasal polyposis is a chronic inflammatory disease often associated with asthma. An ultrastructural study showed that epithelial damage of columnar cells is more pronounced in allergic patients. The length of columnar cell desmosomes was significantly reduced in asthmatics vs. non-asthmatics, and in allergics vs. non-allergics.

Cell contacts in airway epithelium in asthmatics are weakened, which may be an intrinsic feature or due to the presence of eosinophils producing toxic proteins.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis , 2005. , p. 62
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 5
Keywords [en]
Anatomy, Desmosomes, tight junctions, major basic protein, eosinophil, cytokines, epithelial damage.
Keywords [sv]
Anatomi
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:uu:diva-4775ISBN: 91-554-6142-5 (print)OAI: oai:DiVA.org:uu-4775DiVA, id: diva2:165715
Public defence
2005-03-07, B7:113a, BMC, Husargatan 3, Uppsala, 13:15 (English)
Opponent
Supervisors
Available from: 2005-02-14 Created: 2005-02-14 Last updated: 2018-01-13Bibliographically approved
List of papers
1. Effects of the cationic protein poly-L-arginine on airway epithelial cells in vitro
Open this publication in new window or tab >>Effects of the cationic protein poly-L-arginine on airway epithelial cells in vitro
2002 (English)In: Mediators of Inflammation, ISSN 0962-9351, E-ISSN 1466-1861, Vol. 11, no 3, p. 141-148Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Allergic asthma is associated with an increased number of eosinophils in the airway wall. Eosinophils secrete cationic proteins, particularly major basic protein (MBP). AIM: To investigate the effect of synthetic cationic polypeptides such as poly-L-arginine, which can mimic the effect of MBP, on airway epithelial cells. METHODS: Cultured airway epithelial cells were exposed to poly-L-arginine, and effects were determined by light and electron microscopy. RESULTS: Poly-L-arginine induced apoptosis and necrosis. Transmission electron microscopy showed mitochondrial damage and changes in the nucleus. The tight junctions were damaged, as evidenced by penetration of lanthanum. Scanning electron microscopy showed a damaged cell membrane with many pores. Microanalysis showed a significant decrease in the cellular content of magnesium, phosphorus, sodium, potassium and chlorine, and an increase in calcium. Plakoglobin immunoreactivity in the cell membrane was decreased, indicating a decrease in the number of desmosomes CONCLUSIONS: The results point to poly-L-arginine induced membrane damage, resulting in increased permeability, loss of cell-cell contacts and generalized cell damage.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-92575 (URN)10.1080/09622935020138172 (DOI)1781659 (PubMedID)
Available from: 2005-02-14 Created: 2005-02-14 Last updated: 2017-12-14Bibliographically approved
2. Effect of cytokines on ICAM-1 and ZO-1 expression on human airway epithelial cells.
Open this publication in new window or tab >>Effect of cytokines on ICAM-1 and ZO-1 expression on human airway epithelial cells.
2005 (English)In: Cell Biol Int, ISSN 1065-6995, Vol. 29, no 9, p. 768-77Article in journal (Refereed) Published
Identifiers
urn:nbn:se:uu:diva-79752 (URN)16087364 (PubMedID)
Available from: 2006-04-13 Created: 2006-04-13 Last updated: 2011-01-11
3. Ultrastructure of bronchial biopsies from patients with allergic and non-allergic asthma
Open this publication in new window or tab >>Ultrastructure of bronchial biopsies from patients with allergic and non-allergic asthma
Show others...
2005 (English)In: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 99, no 4, p. 429-443Article in journal (Refereed) Published
Abstract [en]

Epithelial damage is commonly found in airways of asthma patients. The aim of this study was to investigate epithelial damage in allergic and non-allergic asthma at the ultrastructural level.

Bronchial biopsies obtained from patients with allergic asthma (n=11n=11), non-allergic asthma (n=7n=7), and healthy controls (n=5n=5) were studied by transmission electron microscopy.

Epithelial damage was found to be extensive in both asthma groups. Both in basal and in columnar cells, relative desmosome length was reduced by 30–40%. In columnar cells, half-desmosomes (i.e., desmosomes of which only one side was present) were frequently noticed. Eosinophils showing piece-meal degranulation were commonly observed in allergic asthma. Degranulating mast cells were more often observed in allergic asthma. Goblet cell hyperplasia was only found in allergic asthma. Lymphocytes were increased in both groups. In both groups, the lamina densa of the basal lamina was thicker than the control by about 40–50%. In allergic asthma the lamina densa was irregular with focal thickening.

While there was always a tendency for changes (epithelial damage, desmosomes, degranulating mast cells, basal lamina) to be more extensive in allergic asthma compared to non-allergic asthma, there was no significant difference between the two groups in this respect. Reduced desmosomal contact may be an important factor in the epithelial shedding observed in patients with asthma.

Keywords
Adult, Asthma/*pathology, Basement Membrane/ultrastructure, Biopsy/methods, Bronchi/*ultrastructure, Bronchoscopy/methods, Desmosomes/ultrastructure, Eosinophils/ultrastructure, Female, Goblet Cells/ultrastructure, Humans, Lymphocytes/ultrastructure, Male, Mast Cells/ultrastructure, Microscopy; Electron; Transmission, Research Support; Non-U.S. Gov't, Respiratory Mucosa/ultrastructure
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-92577 (URN)10.1016/j.rmed.2004.08.013 (DOI)15763449 (PubMedID)
Note

on behalf of the BHR-group 1

Available from: 2005-02-14 Created: 2005-02-14 Last updated: 2017-12-14Bibliographically approved
4. Attachment of columnar airway epithelial cells in asthma
Open this publication in new window or tab >>Attachment of columnar airway epithelial cells in asthma
2005 (English)In: Tissue & Cell, ISSN 0040-8166, E-ISSN 1532-3072, Vol. 37, no 2, p. 145-152Article in journal (Refereed) Published
Abstract [en]

Shedding of airway epithelial cells is a common finding in asthma. In this study, the attachment of the airway epithelial cells to the basal lamina (BL) was investigated by transmission electron microscopy (TEM) of biopsies from patients with atopic asthma and healthy controls. The following parameters were quantitatively determined: the height of the epithelium and of the columnar cells, the number of basal cells per 100 microm of basal lamina, the contact surfaces of basal cells or columnar cells with the basal lamina, and between basal cells and columnar cells. In order to compare the quantitative method with previous literature data, measurements were also carried out on rat airway epithelium. Compared to the rat, the columnar cell height in the human is increased, basal cells are smaller, and there is a larger contact area between basal cells and basal lamina, as well as between basal and columnar cells. The contact area between columnar cells and basal lamina is hence less in the human airway. The contact area between columnar cells and basal lamina in asthmatics is significantly less than in healthy controls, due to larger intercellular spaces. It is concluded that attachment of columnar cells to the basal lamina occurs mainly indirectly, via desmosomal attachment to basal cells, and that direct attachment of columnar cells to the basal lamina is weakened in asthmatics.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-94135 (URN)10.1016/j.tice.2004.12.002 (DOI)15748741 (PubMedID)
Note

on behalf of the BHR group 1

Available from: 2006-03-22 Created: 2006-03-22 Last updated: 2017-12-14Bibliographically approved
5. Ultrastructural investigation of epithelial damage in asthmatic and non-asthmatic nasal polyps
Open this publication in new window or tab >>Ultrastructural investigation of epithelial damage in asthmatic and non-asthmatic nasal polyps
2006 (English)In: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 100, no 11, p. 2018-2028Article in journal (Refereed) Published
Abstract [en]

Nasal polyposis is a poorly understood chronic inflammatory disease often associated with asthma. As nasal polyps and asthma both are associated with massive eosinophil infiltration, they may share a common pathophysiological mechanism. Many genetic and autoimmune diseases may result from altered expression or function of cell adhesion molecules such as desmosomes. A transmission electron microscopical study was carried out on tissue from 15 patients suffering from nasal polyps, to investigate if there are changes in desmosomes in nasal polyps from asthmatic and/or allergic patients versus non-asthmatic versus non-allergic patients. In allergic patients the damage to columnar cells was more extensive than in non-allergic patients. Massive infiltration of eosinophils was observed in epithelium and connective tissue in all groups. No significant difference in thickness of the basal lamina was found between any of the groups. All patients had dilated capillaries in the connective tissue. The intercellular space between the epithelial cells was smallest in the asthmatic non-allergic group. The relative length of columnar cell or basal cell desmosomes was reduced in patients with asthma or allergy, compared to non-allergic, non-asthmatic patients. Hence, there appears to be a weakness in the desmosomes in asthmatics and allergics. Epithelial shedding may play an important rote in the pathophysiological process of a multifactorial disease such as asthma.

Keywords
nasal polyposis, asthma, epithelial damage, desmosomes, eosinophils
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-92579 (URN)10.1016/j.rmed.2006.02.012 (DOI)000241709900020 ()16580832 (PubMedID)
Available from: 2005-02-14 Created: 2005-02-14 Last updated: 2017-12-14Bibliographically approved

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