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Ultrastructural investigation of epithelial damage in asthmatic and non-asthmatic nasal polyps
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
2006 (English)In: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 100, no 11, 2018-2028 p.Article 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.

Place, publisher, year, edition, pages
2006. Vol. 100, no 11, 2018-2028 p.
Keyword [en]
nasal polyposis, asthma, epithelial damage, desmosomes, eosinophils
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-92579DOI: 10.1016/j.rmed.2006.02.012ISI: 000241709900020PubMedID: 16580832OAI: oai:DiVA.org:uu-92579DiVA: diva2:165714
Available from: 2005-02-14 Created: 2005-02-14 Last updated: 2011-05-13Bibliographically approved
In thesis
1. Cell Contacts and Airway Epithelial Damage in Asthma
Open this publication in new window or tab >>Cell Contacts and Airway Epithelial Damage in Asthma
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. 62 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 5
Keyword
Anatomy, Desmosomes, tight junctions, major basic protein, eosinophil, cytokines, epithelial damage., Anatomi
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-4775 (URN)91-554-6142-5 (ISBN)
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: 2013-07-24Bibliographically approved

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Roomans, Godfried M.

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