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Implementation of a Permeable Membrane Insert-based Infection System to Study the Effects of Secreted Bacterial Toxins on Mammalian Host Cells
Published on: August 19, 2016
Inhibition of endotoxin effects on cultured human middle ear epithelium by bactericidal permeability-increasing
M J Nell1, B M Albers-Op 't Hof, H K Koerten
1Department of Otorhinolaryngology, Leiden University Medical Center, The Netherlands.
Hypothesis/Background:
Endotoxin can induce morphologic changes to middle ear epithelium, which can disturb the mucociliary clearance system (MCS) and lead to otitis media with effusion (OME). The bactericidal/permeability-increasing (BPI) protein is a major component of neutrophil granules and binds with high affinity to endotoxin. In this study, the capacity to inhibit the effects of endotoxin by rBPI21, a recombinant amino-terminal analog derived from BPI, was investigated on cultured human middle ear epithelium using light microscopy and scanning- and transmission electron microscopy.
Methods:
Human middle ear epithelium was air-exposed cultured on a collagenous underlayer with different additions of endotoxin and rBPI21 to the culture medium. The tissue specimens were inspected after 4 weeks for the number of ciliated and secretory cells, thickness of the mucosal layer, and cell size.
Results:
The morphologic changes induced by endotoxin were increased thickness of the mucosal layer and increased number of secretory cells. These changes were significantly diminished or even absent when endotoxin was added with rBPI21 to the culture medium.
Conclusion:
rBPI21 can inhibit morphologic changes in the middle ear epithelium due to endotoxin. Hence, the authors believe that rBPI21 can be a new therapeutic agent in the treatment of OME.
Insights
Recombinant bactericidal/permeability-increasing (BPI) protein 21 (rBPI21) effectively inhibited endotoxin-induced morphologic changes in human middle ear epithelial cells, suggesting its potential for treating otitis media with effusion.
Area of Science:
- Otolaryngology
- Cell Biology
- Immunology
Background:
- Endotoxin causes middle ear epithelial changes, impairing mucociliary clearance and potentially leading to otitis media with effusion (OME).
- Bactericidal/permeability-increasing (BPI) protein binds endotoxin and is found in neutrophil granules.
- rBPI21 is a recombinant analog of BPI investigated for its endotoxin-inhibiting properties.
Purpose of the Study:
- To investigate the capacity of rBPI21 to inhibit endotoxin-induced morphologic changes in cultured human middle ear epithelium.
- To evaluate the impact of rBPI21 on mucociliary clearance system (MCS) components.
Main Methods:
- Cultured human middle ear epithelium was exposed to endotoxin and rBPI21.
- Morphologic assessments included light microscopy, scanning electron microscopy, and transmission electron microscopy.
- Evaluated parameters were ciliated and secretory cell counts, mucosal layer thickness, and cell size after 4 weeks.
Main Results:
- Endotoxin exposure led to increased mucosal thickness and secretory cells.
- rBPI21 significantly diminished or prevented these endotoxin-induced morphologic alterations.
- Cell size and ciliated cell counts remained largely unaffected by endotoxin or rBPI21.
Conclusions:
- rBPI21 demonstrates efficacy in inhibiting endotoxin-induced morphologic changes in middle ear epithelium.
- rBPI21 shows promise as a novel therapeutic agent for otitis media with effusion (OME).
- Further research is warranted to explore rBPI21's therapeutic potential in OME treatment.
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