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Complement activation and expression of membrane regulators in the middle ear mucosa in otitis media with effusion
M Närkiö-Mäkelä1, J Jero, S Meri
1Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, Department of Otorhinolaryngology, Helsinki University Central Hospital, Helsinki, Finland.
Abstract:
The aetiopathogenesis of chronic otitis media with effusion (OME) in children is not yet fully understood. OME is characterized by metaplasia of the epithelium and accumulation of sticky, glue-like effusion in the middle ear containing different mediators of inflammation, including activation fragments of the complement system. Here we examined whether the fluid phase complement activation is reflected in the middle ear mucosa and how the mucosa is protected against the cytolytic activity of complement. Mucosal biopsies from 18 middle ears of children with a history of chronic OME were taken. The biopsies were analysed by immunofluorescence microscopy after staining for complement fragments iC3b/C3c, C3d and C9, and regulators membrane cofactor protein (MCP; CD46), decay-accelerating factor (DAF; CD55) and protectin (CD59). There was a strong staining for iC3b/C3c, and a weaker one for C3d and C9 on the surface of the middle ear epithelial cells of OME patients but not in controls without OME. MCP was expressed on the hyperplastic three to four outer cell layers of the epithelium, while CD59 was expressed throughout the middle ear mucosa. The results suggest a strong ongoing complement activation and consequent inflammation in the middle ear cavity. Unrestricted complement damage of the epithelial lining is prevented by the strong expression of MCP and CD59.
Insights
Chronic otitis media with effusion (OME) in children involves complement activation in the middle ear. Protective regulators prevent epithelial damage, suggesting ongoing inflammation.
Area of Science:
- Immunology
- Otolaryngology
- Pediatrics
Background:
- Chronic otitis media with effusion (OME) in children is poorly understood.
- OME involves middle ear effusion and inflammation, with complement system involvement.
- The role of complement activation and regulation in OME mucosa is unclear.
Purpose of the Study:
- To investigate complement activation in the middle ear mucosa of children with OME.
- To determine how the middle ear mucosa is protected from complement-mediated damage.
Main Methods:
- Analysis of middle ear mucosal biopsies from 18 children with chronic OME.
- Immunofluorescence microscopy to detect complement fragments (iC3b/C3c, C3d, C9) and regulators (MCP, DAF, CD59).
Main Results:
- Strong presence of complement fragments (iC3b/C3c, C3d, C9) on middle ear epithelial cells in OME patients.
- Expression of membrane cofactor protein (MCP) on hyperplastic epithelial layers.
- Widespread expression of protectin (CD59) throughout the middle ear mucosa.
Conclusions:
- Evidence of ongoing complement activation and inflammation in the middle ear of children with OME.
- MCP and CD59 play crucial roles in protecting the middle ear epithelium from complement-induced damage.
- Findings contribute to understanding OME pathogenesis and potential therapeutic targets.