Imamura Y, Yanagihara K, Fukuda Y, Kaneko Y, Seki M, Izumikawa K, Miyazaki Y, Hirakata Y, Sawa T, Wiener-Kronish J P, Kohno S
Second Dept of Internal Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
Eur Respir J. 2007 May;29(5):965-8. doi: 10.1183/09031936.00147406. Epub 2007 Feb 14.
Pseudomonas aeruginosa is one of the most important pathogens in patients with chronic airway conditions, such as cystic fibrosis and diffuse panbronchiolitis. Type III secretion system-mediated virulence factors contribute to the lung damage in chronic P. aeruginosa infection. The effects of the anti-PcrV immunoglobulin (Ig)G, which blocks the type III secretion system, were evaluated in a mouse model of chronic P. aeruginosa infection. On bacteriological examination, anti-PcrV IgG showed no bactericidal effects. On bronchoalveolar lavage fluid (BALF) analysis, total cell number and neutrophil ratios in the anti-PcrV IgG-treated groups were lower than those in the control group. In addition, macrophage inflammatory protein-2, tumour necrosis factor-alpha, and interleukin-beta concentrations in BALF were lower in the anti-PcrV IgG-treated groups when compared with controls. Plasma anti-PcrV IgG titre was elevated after administration of anti-PcrV IgG. Although plasma titre decreased gradually, a significant concentration was maintained during the experimental period. These data suggest that anti-PcrV immunoglobulin G reduces the inflammatory reaction caused by chronic Pseudomonas aeruginosa respiratory infection and may be useful in treating respiratory diseases.
铜绿假单胞菌是慢性气道疾病患者(如囊性纤维化和弥漫性泛细支气管炎患者)最重要的病原体之一。III型分泌系统介导的毒力因子会导致慢性铜绿假单胞菌感染中的肺部损伤。在慢性铜绿假单胞菌感染的小鼠模型中评估了阻断III型分泌系统的抗PcrV免疫球蛋白(Ig)G的作用。在细菌学检查中,抗PcrV IgG未显示出杀菌作用。在支气管肺泡灌洗(BALF)分析中,抗PcrV IgG治疗组的总细胞数和中性粒细胞比例低于对照组。此外,与对照组相比,抗PcrV IgG治疗组BALF中的巨噬细胞炎性蛋白-2、肿瘤坏死因子-α和白细胞介素-β浓度较低。给予抗PcrV IgG后,血浆抗PcrV IgG滴度升高。虽然血浆滴度逐渐下降,但在实验期间仍维持在显著浓度。这些数据表明,抗PcrV免疫球蛋白G可减轻慢性铜绿假单胞菌呼吸道感染引起的炎症反应,可能对治疗呼吸道疾病有用。