Complement-regulator factor H and related proteins in otitis media with effusion.
Otitis media with effusion (OME) is a common disease in childhood. It is characterized by chronic inflammation in which the proinflammatory activity of the complement (C) system is one of the underlying factors. The C system becomes strongly activated in the middle ear effusion (MEE) fluid, but the reasons for this are not known. Here we demonstrate by using complement Bb fragment ELISA that MEE specimens strongly activate the alternative C pathway (AP) in normal human serum (NHS). Some of the MEEs were also found to promote lysis of rabbit erythrocytes by NHS. These findings indicated a disturbance in the fluid-phase regulation of the AP in MEE. The main regulator of the AP, factor H (FH), and proteins structurally related to it (FHL-1, FHR-1, -2, -3, and -4) were present in the MEE fluids of OME patients. Relative to serum, the FHR proteins were more abundant in the MEEs. In addition, we detected the recently discovered 65-kDa FH-related protein FHR-5 in the MEE. The FHR proteins share binding sites with FH in the C3d region of C3b. Thus they may compete with FH in binding to C3b and interfere with the regulatory activity of FH. Consequently, a disturbance in AP control in the MEE may lead to an ongoing excessive C activation and inflammation in OME.
Närkiö-Mäkelä
M
M
Department of Bacteriology and Immunology, University of Helsinki, Helsinki, Finland.
Hellwage
J
J
Tahkokallio
O
O
Meri
S
S
D001053:Apolipoproteins / Q000032:analysis*; D001667:Binding, Competitive; D001798:Blood Proteins / Q000032:analysis*; D015153:Blotting, Western; D001826:Body Fluids / Q000737:chemistry*; D002648:Child; D002675:Child, Preschool; D003179:Complement C3b / Q000378:metabolism; D003180:Complement C3b Inactivator Proteins; D015933:Complement C3d / Q000378:metabolism; D011415:Complement Factor B / Q000378:metabolism; D017242:Complement Factor H / Q000032:analysis*; D003170:Complement Pathway, Alternative; D003165:Complement System Proteins; D005260:Female; D006462:Hemolytic Plaque Technique; D006801:Humans; D007223:Infant; D008876:Middle Ear Ventilation; D010034:Otitis Media with Effusion / Q000378:metabolism* / Q000601:surgery
D001053:Apolipoproteins; D001798:Blood Proteins; C493495:CFH protein, human; C517621:CFHR1 protein, human; C105970:CFHR3 protein, human; C105092:CFHR4 protein, human; C432223:CFHR5 protein, human; D003180:Complement C3b Inactivator Proteins; C100631:factor H-related protein 1; C100632:factor H-related protein 2; C075242:factor H-related protein p37; D003179:Complement C3b; D015933:Complement C3d; D017242:Complement Factor H; D003165:Complement System Proteins; D011415:Complement Factor B