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…
Contents
1. Introduction
Atopy and asthma
Structure of the airway wall
Cell-cell contacts in epithelia
Adhesion molecules
The inflammatory response in asthma
Inflammatory cells
Cytokines
Polyps and asthma
Rhinitis and asthma
Epithelial damage in asthma
Treatment
2. Aims
3. Materials and Methods
Cell culture
Induction of cell cultures
Bronchial biopsies
Rats
Nasal polyps
Transmission electron microscopy
Scanning electron microscopy
Immunocytochemical studies
Light microscopy
Cell viability test
DNA labeling
Flow cytometry analysis of ICAM-1
Western blot
X-ray microanalysis
Statistics
4 . Results
Paper I
Paper II
Paper III
Paper IV
Paper V
5. Discussion
Studies on human tissues in situ
Epithelial damage
Desmosomes
Eosinophils
Neutrophils
Mast cells
Intercellular space
Basal lamina
Experimental studies
Effects of poly-L-arginine on airway epithe-
lial cells
Effects of different cytokines on bronchial
epithelial cells
6. Conclusions and Future
Perspectives
7. Acknowledgements
8. References
Author: Shahana, Shahida
Source: Uppsala University Library
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