Complement activation by salivary agglutinin is secretor status dependent

• Published in: Biological Chemistry
• Main Authors: Gunput, Sabrina T.G., Ligtenberg, Antoon J.M., Terlouw, Bas, Brouwer, Mieke, Veerman, Enno C.I., Wouters, Diana
• Format: Article in Journal/Newspaper
• Language: English
• Published: Walter de Gruyter GmbH 2014
• Subjects: Clinical Biochemistry; Molecular Biology; Biochemistry; Anguilla anguilla
• Online Access: http://dx.doi.org/10.1515/hsz-2014-0200; http://www.degruyter.com/view/j/bchm.2015.396.issue-1/hsz-2014-0200/hsz-2014-0200.xml; https://www.degruyter.com/document/doi/10.1515/hsz-2014-0200/xml; https://www.degruyter.com/document/doi/10.1515/hsz-2014-0200/pdf

Abstract After mucosal damage or gingival inflammation, complement proteins leak into the oral cavity and mix with salivary proteins such as salivary agglutinin (SAG/gp-340/DMBT1). This protein is encoded by the gene Deleted in Malignant Brain Tumors 1 ( DMBT1 ), and it aggregates bacteria, viruses and fungi, and activates the lectin pathway of the complement system. In the lectin pathway, carbohydrate structures on pathogens or altered self cells are recognized. SAG is highly glycosylated, partly on the basis of the donor’s blood group status. Whereas secretors express Lewis b, Lewis y, and antigens from the ABO-blood group system on SAG, non-secretors do not. Through mannose-binding lectin (MBL) binding and C4 deposition assays, we aimed to identify the chemical structures on SAG that are responsible for complement activation. The complement-activating properties of SAG were completely abolished by oxidation of its carbohydrate moiety. SAG-mediated activation of complement was also inhibited in the presence of saccharides such as fucose and Lewis b carbohydrates, and also after pretreatment with the fucose-binding lectin, Anguilla anguilla agglutinin. Complement activation was significantly ( p <0.01) higher in secretors than in non-secretors. Our results suggest that fucose-rich oligosaccharide sidechains, such as Lewis b antigens, are involved in the activation of complement by SAG.