title: Dual host-defence functions of SPLUNC2/PSP and synthetic peptides derived from the protein.
abstract: PSP (parotid secretory protein)/SPLUNC2 (short palate, lung and nasal epithelium clone 2) is expressed in human salivary glands and saliva. The protein exists as an N-glycosylated and non-glycosylated form and both appear to induce agglutination of bacteria, a major antibacterial function for salivary proteins. Both forms of PSP/SPLUNC2 bind LPS (lipopolysaccharide), suggesting that the protein may also play an anti-inflammatory role. Based on the predicted structure of PSP/SPLUNC2 and the location of known antibacterial and anti-inflammatory peptides in BPI (bactericidal/permeability-increasing protein) and LBP (LPS-binding protein), we designed GL13NH2 and GL13K, synthetic peptides that capture these proposed functions of PSP/SPLUNC2. GL13NH3 agglutinates bacteria, leading to increased clearance by macrophages and reduced spread of infection in a plant model. GL13K kills bacteria with a minimal inhibitory concentration of 5-10 μg/ml, kills bacteria in biofilm and retains activity in 150 mM NaCl and 50% saliva. Both peptides block endotoxin action, but only GL13K appears to bind endotoxin. The peptides do not cause haemolysis, haemagglutination in serum, inhibit mammalian cell proliferation or induce an inflammatory response in macrophages. These results suggest that the GL13NH2 and the modified peptide GL13K capture the biological activity of PSP/SPLUNC2 and can serve as lead compounds for the development of novel antimicrobial and anti-inflammatory peptides.
authors.affiliation: Department of Diagnostic and Biological Sciences, University of Minnesota School of Dentistry, Minneapolis, MN 55455, USA. sugorr@umn.edu
authors.forename: Sven-Ulrik
authors.initials: SU
authors.lastname: Gorr
authors.forename: Mahsa
authors.initials: M
authors.lastname: Abdolhosseini
authors.forename: Anuradha
authors.initials: A
authors.lastname: Shelar
authors.forename: Julie
authors.initials: J
authors.lastname: Sotsky
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism; D001424:Bacterial Infections / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D008070:Lipopolysaccharides / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D011485:Protein Binding; D012463:Saliva / Q000378:metabolism; D012471:Salivary Proteins and Peptides / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; C045623:BPIFA2 protein, human; D008070:Lipopolysaccharides; D010446:Peptide Fragments; D012471:Salivary Proteins and Peptides