title: The bacteria binding glycoprotein salivary agglutinin (SAG/gp340) activates complement via the lectin pathway.
abstract: Salivary agglutinin (SAG), also known as gp-340 and Deleted in Malignant Brain Tumours 1, is a glycoprotein that is present in tears, lung fluid and mucosal surfaces along the gastrointestinal tract. It is encoded by the Deleted in Malignant Brain Tumours 1 gene, a member of the Scavenger Receptor Cysteine Rich group B protein superfamily. SAG aggregates bacteria thus promoting their clearance from the oral cavity and activates the complement system. Complement proteins may enter the oral cavity in case of serum leakage, which occurs after mucosal damage. The purpose of this study was to investigate the mode of complement activation. We showed a dose-dependent C4 deposition on SAG-coated microplates showing that either the classical or lectin pathway of complement was activated. Antibodies against mannose binding lectin inhibited C4 deposition and SAG induced no C4 deposition in MBL deficient sera showing SAG activated complement through the MBL pathway. Periodate treatment of SAG abolished MBL pathway activation consistent with an involvement of SAG glycans in complement activation. This provides the first evidence for a role of SAG in complement activation through the MBL pathway and suggests a potential role of SAG as a complement activating factor at the mucosal epithelia.
authors.affiliation: Department of Oral Biochemistry, Academic Centre for Dentistry Amsterdam, Free University and University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Jelani T D
authors.initials: JT
authors.lastname: Leito
authors.forename: Antoon J M
authors.initials: AJ
authors.lastname: Ligtenberg
authors.forename: Michel
authors.initials: M
authors.lastname: van Houdt
authors.forename: Timo K
authors.initials: TK
authors.lastname: van den Berg
authors.forename: Diana
authors.initials: D
authors.lastname: Wouters
mesh_terms: D002135:Calcium-Binding Proteins; D037582:Complement Pathway, Mannose-Binding Lectin / Q000276:immunology*; D004268:DNA-Binding Proteins; D006801:Humans; D018928:Immunity, Mucosal / Q000276:immunology; D011956:Receptors, Cell Surface / Q000276:immunology* / Q000378:metabolism; D025521:Tumor Suppressor Proteins
chemical_list: D002135:Calcium-Binding Proteins; C108174:DMBT1 protein, human; D004268:DNA-Binding Proteins; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins