The parotid secretory protein BPIFA2 is a salivary surfactant that affects LPS action

Saliva plays important roles in the mastication, swallowing and digestion of food, speech and lubrication of oral mucosa, antimicrobial and anti-inflammatory activity and control of body temperature in grooming animals. The salivary protein BPIFA2 (BPI fold containing family A member 2; former names: Parotid Secretory Protein, PSP, SPLUNC2, C20orf70) is related to lipid-binding and LPS-binding proteins expressed in mucosa. Indeed, BPIFA2 binds LPS but the physiological role of BPIFA2 remains to be determined. To address this question, Bpifa2 knockout (Bpifa2tm1(KOMP)Vlcg) (KO) mice were phenotyped with a special emphasis on saliva and salivary glands. Saliva collected from KO mice was less able to spread on a hydrophobic surface than wild-type saliva and the surface tension of KO saliva was close to that of water. These data suggest that BPIFA2 is a salivary surfactant that is mainly responsible for the low surface tension of mouse saliva. The reduced surfactant activity of KO saliva did not affect consumption of dry food or grooming, but saliva from KO mice contained less LPS than wild-type saliva. Indeed, mice lacking BPIFA2 responded to ingested LPS with an increased stool frequency, suggesting that BPIFA2 plays a role in the solubilization and activity of ingested LPS. Consistent with these findings, BPIFA2-depleted mice also showed increased insulin secretion and metabolomic changes that were consistent with a mild endotoxemia. These results support the distal physiological function of a salivary protein and reinforce the connection between oral biology and systemic disease.