Seshagiri Rao Nandula1,2, Ian Huxford3, Thomas T Wheeler4, Conrado Aparicio3, Sven-Ulrik Gorr1. 1. Department of Diagnostic and Biological Sciences, University of Minnesota School of Dentistry, Minneapolis, MN, USA. 2. Department of Biochemistry & Molecular Biology, George Washington University, Washington, DC, USA. 3. Department of Restorative Sciences, University of Minnesota School of Dentistry, Minneapolis, MN, USA. 4. Cawthron Institute, Private Bag 2, Nelson, 7042, New Zealand.
Abstract
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.
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.
Authors: Jennifer A Bartlett; Jennifer Bartlett; Lokesh Gakhar; Jon Penterman; Pradeep K Singh; Pradeep Singh; Rama K Mallampalli; Edith Porter; Paul B McCray Journal: Biochem Soc Trans Date: 2011-08 Impact factor: 5.407
Authors: Kristin Scoggin; Rachel Lynch; Jyotsana Gupta; Aravindh Nagarajan; Maxwell Sheffield; Ahmed Elsaadi; Christopher Bowden; Manuchehr Aminian; Amy Peterson; L Garry Adams; Michael Kirby; David W Threadgill; Helene L Andrews-Polymenis Journal: PLoS Genet Date: 2022-04-13 Impact factor: 6.020