Complement activation and expression of membrane regulators in the middle ear mucosa in otitis media with effusion.
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.
Närkiö-Mäkelä
M
M
Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, Department of Otorhinolaryngology, Helsinki University Central Hospital, Helsinki, Finland.
Jero
J
J
Meri
S
S
D015703:Antigens, CD / Q000276:immunology; D018958:CD55 Antigens / Q000378:metabolism; D018957:CD59 Antigens / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003167:Complement Activation; D003179:Complement C3b / Q000378:metabolism; D015932:Complement C3c / Q000378:metabolism; D015933:Complement C3d / Q000378:metabolism; D003186:Complement C9 / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D004432:Ear, Middle / Q000276:immunology* / Q000473:pathology; D004848:Epithelium / Q000276:immunology / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D008297:Male; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000276:immunology; D009092:Mucous Membrane / Q000276:immunology / Q000473:pathology; D010034:Otitis Media with Effusion / Q000276:immunology* / Q000473:pathology
D015703:Antigens, CD; C497857:CD46 protein, human; D018958:CD55 Antigens; D018957:CD59 Antigens; D003186:Complement C9; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D003179:Complement C3b; D015932:Complement C3c; D015933:Complement C3d