Dual host-defence functions of SPLUNC2/PSP and synthetic peptides derived from the protein
Dual host-defence functions of SPLUNC2/PSP and synthetic peptides derived from the protein
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DOI：
10.1042/bst0391028
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发表时间：
2011-08-01
影响因子：
3.9
通讯作者：
Sotsky, Julie
中科院分区：
文献类型：
--
作者：
Gorr, Sven-Ulrik;Abdolhosseini, Mahsa;Sotsky, Julie
PSP（腮腺分泌蛋白）/SPLUNC 2（短腭、肺和鼻上皮克隆2）在人唾液腺和唾液中表达。该蛋白以N-糖基化和非糖基化形式存在，并且两者似乎都诱导细菌凝集，这是唾液蛋白的主要抗菌功能。PSP/SPLUNC 2的两种形式都结合LPS（脂多糖），这表明该蛋白质也可能发挥抗炎作用。基于PSP/SPLUNC 2的预测结构以及已知抗菌和抗炎肽在BPI（杀菌/通透性增加蛋白）和LBP（LPS结合蛋白）中的位置，我们设计了GL 13 NH 2和GL 13 K，合成肽捕获PSP/SPLUNC 2的这些功能。GL 13 NH3凝集细菌，导致巨噬细胞清除率增加，并减少植物模型中的感染传播。GL 13 K以5-10 μ g/ml的最小抑制浓度杀死细菌，杀死生物膜中的细菌，并在150 mM NaCl和50%唾液中保持活性。这两种肽都能阻断内毒素作用，但似乎只有GL 13 K能结合内毒素。所述肽不会引起溶血、血清中的血细胞凝集、抑制哺乳动物细胞增殖或诱导巨噬细胞中的炎症反应。这些结果表明，GL 13 NH 2和修饰的肽GL 13 K捕获PSP/SPLUNC 2的生物活性，并可以作为开发新的抗微生物和抗炎肽的先导化合物。
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 mu g/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.