Cell Contacts and Airway Epithelial Damage in Asthma
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...
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| Format: | Doctoral Thesis |
| Language: | English |
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Uppsala universitet, Institutionen för medicinsk cellbiologi
2005
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| Online Access: | http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-4775 http://nbn-resolving.de/urn:isbn:91-554-6142-5 |
| Summary: | 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. |
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