Dual function of the long pentraxin PTX3 in resistance against pulmonary infection with Klebsiella pneumoniae in transgenic mice

被引:92
作者
Soares, Adriana C.
Souza, Danielle G.
Pinho, Vanessa
Vieira, Angelica T.
Nicoli, Jacques R.
Cunha, Fernando Q.
Mantovani, Alberto
Reis, Luiz Fernando L.
Dias, Adriana A. M.
Teixeira, Mauro M.
机构
[1] Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Bioquim & Imunol, BR-31270901 Belo Horizonte, MG, Brazil
[2] Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Microbiol, BR-31270901 Belo Horizonte, MG, Brazil
[3] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Farmacol, Ribeirao Preto, Brazil
[4] Ist Ric Farmacol Mario Negri, Milan, Italy
[5] Ist Clin Humanitas, Milan, Italy
[6] Ludwig Inst Canc Res, Sao Paulo, Brazil
[7] Hosp Canc AC Camargo, Ctr Tratamento & Pesquisa, Sao Paulo, Brazil
基金
巴西圣保罗研究基金会;
关键词
neutrophil; bacterial infection; pentraxin;
D O I
10.1016/j.micinf.2005.12.017
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The long pentraxin PTX3 is expressed during acute inflammation and appears to control nitric oxide (NO) and tumor necrosis factor (TNF)alpha production. In the present study, the physiological function of PTX3 was investigated in a model of pulmonary infection caused by the Gram-negative bacterium Klebsiella pneumoniae. Transgenic mice expressing multiple copies of PTX3 under the control of its own promoter were used to assess lethality rates, bacterial counts and inflammatory indices following pulmonary infection of mice. Expression of PTX3 is enhanced during pulmonary infection in wild-type mice. In transgenic mice given a high inoculum, overt PTX3 expression was associated with faster lethality. Faster lethality correlated with enhanced nitrate in plasma, an inability of neutrophils to migrate to lung tissue and greater dissemination of bacteria to blood at 20 h after infection. In contrast, transgenic PTX3 expression conferred protection to mice given lower pulmonary inocula. In the latter experiments, there was enhanced TNF-alpha production, greater neutrophil influx and phagocytosis of bacteria by migrated neutrophils. By controlling the production of TNF-alpha and NO, and depending on the intensity of the inflammatory response induced by a given inoculum, the expression of PTX3 may favor or disfavor the influx of neutrophils and the ability of the murine host to deal with pulmonary infection with K. pneumoniae. These experiments highlight the delicate balance that exists among the various mediators that control the inflammatory response and suggest that PTX3 is an essential part of the ability of a host to deal with bacterial infection. (c) 2006 Elsevier SAS. All rights reserved.
引用
收藏
页码:1321 / 1329
页数:9
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