Complement activation by salivary agglutinin is secretor status dependent

Area of Science:

• Oral immunology
• Complement system biology
• Glycobiology

Background:

• Mucosal damage and gingival inflammation allow complement proteins to enter the oral cavity.
• Salivary agglutinin (SAG), encoded by DMBT1, aggregates microbes and activates the complement lectin pathway.
• SAG's glycosylation varies with blood group, influencing its function.

Purpose of the Study:

• To identify specific chemical structures on SAG responsible for complement activation.
• To investigate the role of glycosylation and blood group status in SAG-mediated complement activation.

Main Methods:

• Mannose-binding lectin (MBL) binding assays.
• C4 deposition assays to measure complement activation.
• Chemical modification (oxidation) and inhibition studies using specific saccharides and lectins.

Main Results:

• Oxidation of SAG's carbohydrate moiety abolished its complement-activating properties.
• Fucose and Lewis b carbohydrates inhibited SAG-mediated complement activation.
• Complement activation was significantly higher in secretors (expressing Lewis b) than non-secretors.

Conclusions:

• Fucose-rich oligosaccharide side chains, particularly Lewis b antigens, are crucial for SAG's activation of the complement system.
• Blood group-dependent glycosylation of SAG influences oral immune responses.