Role of LecA and LecB Lectins in Pseudomonas aeruginosa-Induced Lung Injury and Effect of Carbohydrate Ligands

被引:239
作者
Chemani, Chanez [1 ,2 ]
Imberty, Anne [3 ]
de Bentzmann, Sophie [4 ]
Pierre, Maud [1 ,2 ,5 ]
Wimmerova, Michaela [6 ,7 ]
Guery, Benoit P. [1 ,2 ]
Faure, Karine [1 ,2 ]
机构
[1] Univ Lille 2, Fac Med, EA 2689, IFR 114, F-59045 Lille, France
[2] CHRU, Lille, France
[3] CERMAV CNRS, Grenoble, France
[4] CNRS, UPR9027, IFR88, Marseille, France
[5] Univ Lille 2, Hop Jeanne Flandre, EA 3925, Pediat Clin,IFR 114, F-59045 Lille, France
[6] Masaryk Univ, NCBR, Brno, Czech Republic
[7] Masaryk Univ, Dept Biochem, Brno, Czech Republic
关键词
PA-IIL; STRUCTURAL BASIS; GALACTOPHILIC LECTIN; BINDING; IL; ADHESION; HOST; LOCALIZATION; ADHERENCE; VIRULENCE;
D O I
10.1128/IAI.01204-08
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Pseudomonas aeruginosa is a frequently encountered pathogen that is involved in acute and chronic lung infections. Lectin-mediated bacterium-cell recognition and adhesion are critical steps in initiating P. aeruginosa pathogenesis. This study was designed to evaluate the contributions of LecA and LecB to the pathogenesis of P. aeruginosa-mediated acute lung injury. Using an in vitro model with A549 cells and an experimental in vivo murine model of acute lung injury, we compared the parental strain to lecA and lecB mutants. The effects of both LecA-and Lec B-specific lectin-inhibiting carbohydrates (alpha-methyl-galactoside and alpha-methyl-fucoside, respectively) were evaluated. In vitro, the parental strain was associated with increased cytotoxicity and adhesion on Lambda 549 cells compared to the lecA and lecB mutants. In vivo, the P. aeruginosa-induced increase in alveolar barrier permeability was reduced with both mutants. The bacterial burden and dissemination were decreased for both mutants compared with the parental strain. Coadministration of specific lectin inhibitors markedly reduced lung injury and mortality. Our results demonstrate that there is a relationship between lectins and the pathogenicity of P. aeruginosa. Inhibition of the lectins by specific carbohydrates may provide new therapeutic perspectives.
引用
收藏
页码:2065 / 2075
页数:11
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