New Findings: What is the central question of this study? The salivary protein BPIFA2 binds lipopolysaccharide, but its physiological function is not known. This study uses a new knockout mouse model to explore the physiological role of BPIFA2 in the oral cavity and systemic physiology. What is the main finding and its importance? BPIFA2 is a crucial surfactant in mouse saliva. In its absence, saliva exhibits the surface tension of water. Depletion of BPIFA2 affects salivary and ingested lipopolysaccharide and leads to systemic sequelae that include increased insulin secretion and metabolomic changes. These results suggest that the lipopolysaccharide-binding activity of BPIFA2 affects the activity of ingested lipopolysaccharide in the intestine and that BPIFA2 depletion causes mild metabolic endotoxaemia. Abstract: Saliva plays important roles in the mastication, swallowing and digestion of food, speech and lubrication of the oral mucosa, antimicrobial and anti-inflammatory activities, and the control of body temperature in grooming animals. The salivary protein BPIFA [BPI fold containing family A member 2; former names: parotid secretory protein (PSP), SPLUN2 and C20orf70] is related to lipid-binding and lipopolysaccharide (LPS)-binding proteins expressed in the 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 emphasis on the saliva and salivary glands. Stimulated whole 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 endotoxaemia. These results support the distal physiological function of a salivary protein and reinforce the connection between oral biology and systemic disease.
Bibliographical noteFunding Information:
We thank H. Hirt, University of Minnesota, for assistance with initial assays and helpful discussions. S. Ruhl, University at Buffalo is thanked for helpful discussions of unpublished data. We thank staff at the University of Minnesota Research Animals Resource for assistance with colony maintenance and sample collection. The mouse strain used for this research project was generated by the trans-NIH Knock-Out Mouse Project (KOMP) and obtained from the KOMP Repository (www.komp.org). National Institutes of Health and the CSD Consortium funded the generation of gene-targeted embryonic stem cells for 8500 genes in the KOMP Program. These resources are archived and distributed by the KOMP Repository at the University of California Davis and Children's Hospital Oakland Research Institute.
This study was funded in part by United States Public Health Service grant R01DE017989 and research funds generously provided by the University of Minnesota School of Dentistry, which is gratefully acknowledged. The mouse strain used for this research project was generated by the trans‐NIH Knock‐Out Mouse Project (KOMP) and obtained from the KOMP Repository ( www.komp.org ). US National Institutes of Health grants to Velocigene at Regeneron Inc. (U01HG004085) and the CSD Consortium (U01HG004080) funded the generation of gene‐targeted embryonic stem cells for 8500 genes in the KOMP Program. These resources are archived and distributed by the KOMP Repository at the University of Californina Davis and Children's Hospital Oakland Research Institute (U42RR024244).
© 2020 The Authors. Experimental Physiology © 2020 The Physiological Society
- contact angle
- surface tension
PubMed: MeSH publication types
- Journal Article
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't