Aerosolized bovine lactoferrin reduces neutrophils and pro-inflammatory cytokines in mouse models of Pseudomonas aeruginosa lung infections.

P. Valenti, A. Frioni, A. Rossi, Serena Ranucci, Ida De Fino, A. Cutone, L. Rosa, A. Bragonzi, F. Berlutti
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引用次数: 47

Abstract

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 106 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.
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雾化牛乳铁蛋白减少中性粒细胞和促炎细胞因子在小鼠模型铜绿假单胞菌肺部感染。
乳铁蛋白(Lf)是先天免疫的一种铁螯合糖蛋白,由外分泌腺和中性粒细胞在感染/炎症部位产生,是气道分泌物中最丰富的防御分子之一。Lf是一种多效性分子,具有抗菌和抗炎功能。这些特性可能在以过度炎症反应为特征的气道感染中发挥相关作用,如囊性纤维化(CF)受试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Lf (bLf)在铜绿假单胞菌急性和慢性肺部感染小鼠模型中的效果。C57BL/6NCrl小鼠经气管内给药,分别感染铜绿假单胞菌PAO1(急性感染)或MDR-RP73菌株(慢性感染)106 CFUs。在急性和慢性感染中,雾化bLf导致细菌负荷不显著减少,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,blf治疗小鼠的体重恢复速度更快,程度高于对照组小鼠。这些发现为bLf作为一般健康介质的益处及其潜在的治疗应用提供了新的见解。
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