Mast cells mediate Pseudomonas aeruginosa lipopolysaccharide-induced lung inflammation in rat

Mast cells mediate Pseudomonas aeruginosa lipopolysaccharide-induced lung inflammation in rat
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DOI:
10.1007/s10096-011-1530-5
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发表时间:
2012-08-01
影响因子:
4.5
通讯作者:
Gay-Queheillard, J.
Gay-Queheillard, J.
中科院分区:
医学3区
文献类型:
--
作者:
Le, B. V.;Khorsi-Cauet, H.;Gay-Queheillard, J.

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活化的肥大细胞已被证明在铜绿假单胞菌肺部感染中起关键作用。然而,目前还没有关于肥大细胞参与铜绿假单胞菌脂多糖(LPS)诱导的肺部炎症的报道。本研究旨在评价肥大细胞在铜绿假单胞菌LPS诱导的大鼠肺部炎症中的作用。肥大细胞的稳定化是通过腹膜内注射克罗埃息进行的。肺内滴注铜绿假单胞菌LPS(5 μ g/kg bw)诱导肺部炎症,并在LPS滴注后4小时评价炎症状态。我们发现活化的肥大细胞可以构成几种炎性细胞因子的关键来源,包括TNF-α、IL-1 β和IL-6。这些细胞可能调节中性粒细胞(PMN)的募集,并通过释放TNF-α和IL-1 β参与肺泡毛细血管通透性的改变。我们还发现,活化的肥大细胞可能参与改变表达的两个上皮紧密连接蛋白(claudin-1和occludin)在急性炎症期。我们的研究结果表明,活化的肥大细胞可能在铜绿假单胞菌LPS诱导的肺部炎症中发挥关键作用。因此,稳定肥大细胞可能是预防和治疗铜绿假单胞菌引起的肺部感染的一种潜在的新方法。
Activated mast cells have been demonstrated to play a pivotal role in Pseudomonas aeruginosa lung infections. However, there is no report about the involvement of mast cells in P. aeruginosa lipopolysaccharide (LPS)-induced lung inflammation. This study aimed at evaluating the role of mast cells in P. aeruginosa LPS-induced lung inflammation in rats. Mast cells stabilization was carried out by intraperitoneal injections of cromolyn. Lung inflammation was induced by the intratracheal instillation of P. aeruginosa LPS (5 mu g/kg bw) and inflammatory status was evaluated 4 h post-LPS instillation. We found that activated mast cells could constitute a pivotal source of several inflammatory cytokines, including TNF-alpha, IL-1 beta, and IL-6. These cells might regulate polymorphonuclear neutrophil (PMN) recruitment and be implicated in the alteration of alveolar-capillary permeability via the release of TNF-alpha and IL-1 beta. We also detected that activated mast cells could be involved in the alteration of the expression of two epithelial tight junction proteins (claudin-1 and occludin) during the acute phase of inflammation. Our results suggest that activated mast cells might play a critical role in P. aeruginosa LPS-induced lung inflammation. Therefore, mast cell stabilization may be a potential novel approach for the prevention and treatment of P. aeruginosa-induced lung infections.