Valenti Piera, Frioni Alessandra, Rossi Alice, Ranucci Serena, De Fino Ida, Cutone Antimo, Rosa Luigi, Bragonzi Alessandra, Berlutti Francesca
a Department of Public Health and Infectious Diseases, Sapienza University, Rome, Italy.
b Infection and Cystic Fibrosis Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS, San Raffaele Scientific Institute, Milan, Italy.
Biochem Cell Biol. 2017 Feb;95(1):41-47. doi: 10.1139/bcb-2016-0050. Epub 2016 Jul 8.
Lactoferrin (Lf), an iron-chelating glycoprotein of innate immunity, produced by exocrine glands and neutrophils in infection/inflammation sites, is one of the most abundant defence molecules in airway secretions. Lf, a pleiotropic molecule, exhibits antibacterial and anti-inflammatory functions. These properties may play a relevant role in airway infections characterized by exaggerated inflammatory response, as in Pseudomonas aeruginosa lung infection in cystic fibrosis (CF) subjects. To verify the Lf role in Pseudomonas aeruginosa lung infection, we evaluated the efficacy of aerosolized bovine Lf (bLf) in mouse models of P. aeruginosa acute and chronic lung infections. C57BL/6NCrl mice were challenged with 10 CFUs of P. aeruginosa PAO1 (acute infection) or MDR-RP73 strain (chronic infection) by intra-tracheal administration. In both acute and chronic infections, aerosolized bLf resulted in nonsignificant reduction of bacterial load but significant decrease of the neutrophil recruitment and pro-inflammatory cytokine levels. Moreover, in chronic infection the bLf-treated mice recovered body weight faster and to a higher extent than the control mice. These findings add new insights into the benefits of bLf as a mediator of general health and its potential therapeutic applications.
乳铁蛋白(Lf)是一种参与固有免疫的铁螯合糖蛋白,由外分泌腺以及感染/炎症部位的中性粒细胞产生,是气道分泌物中含量最为丰富的防御分子之一。Lf是一种具有多种功能的分子,具有抗菌和抗炎作用。这些特性可能在以炎症反应过度为特征的气道感染中发挥重要作用,如囊性纤维化(CF)患者的铜绿假单胞菌肺部感染。为了验证Lf在铜绿假单胞菌肺部感染中的作用,我们评估了雾化牛乳铁蛋白(bLf)在铜绿假单胞菌急性和慢性肺部感染小鼠模型中的疗效。通过气管内给药,用10个铜绿假单胞菌PAO1菌落形成单位(CFU)(急性感染)或多重耐药RP73菌株(慢性感染)对C57BL/6NCrl小鼠进行攻击。在急性和慢性感染中,雾化bLf导致细菌载量无显著降低,但中性粒细胞募集和促炎细胞因子水平显著降低。此外,在慢性感染中,接受bLf治疗的小鼠体重恢复得更快,且恢复程度高于对照小鼠。这些发现为bLf作为整体健康调节因子的益处及其潜在治疗应用提供了新的见解。