Department of Pediatrics, University of Iowa Carver College of Medicine, 240 EMRB, Iowa City, IA 52242, USA.
Biochem Soc Trans. 2011 Aug;39(4):1012-6. doi: 10.1042/BST0391012.
PLUNC (palate, lung and nasal epithelium clone) protein is an abundant secretory product of epithelia throughout the mammalian conducting airways. Despite its homology with the innate immune defence molecules BPI (bactericidal/permeability-increasing protein) and LBP (lipopolysaccharide-binding protein), it has been difficult to define the functions of PLUNC. Based on its marked hydrophobicity and expression pattern, we hypothesized that PLUNC is an airway surfactant. We found that purified recombinant human PLUNC exhibited potent surfactant activity by several different measures, and experiments with airway epithelial cell lines and primary cultures indicate that native PLUNC makes a significant contribution to the overall surface tension in airway epithelial secretions. Interestingly, we also found that physiologically relevant concentrations of PLUNC-inhibited Pseudomonas aeruginosa biofilm formation in vitro without acting directly as a bactericide. This finding suggests that PLUNC protein may inhibit biofilm formation by airway pathogens, perhaps through its dispersant properties. Our data, along with reports from other groups on activity against some airway pathogens, expand on an emerging picture of PLUNC as a multifunctional protein, which plays a novel role in airway defences at the air/liquid interface.
PLUNC(腭、肺和鼻上皮克隆)蛋白是哺乳动物呼吸道上皮细胞的丰富分泌产物。尽管它与先天免疫防御分子 BPI(杀菌/通透性增加蛋白)和 LBP(脂多糖结合蛋白)具有同源性,但 PLUNC 的功能一直难以确定。基于其明显的疏水性和表达模式,我们假设 PLUNC 是一种气道表面活性剂。我们发现纯化的重组人 PLUNC 通过多种不同的方法表现出很强的表面活性剂活性,并且对气道上皮细胞系和原代培养物的实验表明,天然 PLUNC 对气道上皮细胞分泌物的总表面张力有很大贡献。有趣的是,我们还发现生理相关浓度的 PLUNC 可抑制体外铜绿假单胞菌生物膜的形成,而不是直接作为杀菌剂。这一发现表明 PLUNC 蛋白可能通过其分散特性抑制气道病原体生物膜的形成。我们的数据以及其他小组关于对一些气道病原体的活性的报告,扩展了 PLUNC 作为一种多功能蛋白的新认识,该蛋白在气/液界面的气道防御中发挥新的作用。