Pseudomonas aeruginosa in cystic fibrosis: Pyocyanin negative strains are associated with BPI-ANCA and progressive lung disease
Pseudomonas aeruginosa in cystic fibrosis: Pyocyanin negative strains are associated with BPI-ANCA and progressive lung disease
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DOI：
10.1016/j.jcf.2011.03.004
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发表时间：
2011-07-01
影响因子：
5.2
通讯作者：
Hellmark, Thomas
中科院分区：
文献类型：
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作者：
Carlsson, Malin;Shukla, Swati;Hellmark, Thomas
囊性纤维化 (CF) 中慢性铜绿假单胞菌定植的临床后果因人而异，原因未知。抗杀菌/通透性增加蛋白 (BPI-ANCA) 的自身抗体与 CF 的不良预后相关。我们假设 BPI-ANCA 的存在、定植细菌的特性和宿主的临床状况之间存在相关性。我们比较了肺部疾病恶化的 BPI-ANCA 阳性 CF 患者与临床状况稳定的 BPI-ANCA 阴性 CF 患者的铜绿假单胞菌分离株。用分离物刺激上皮细胞（A549）和分离的多形核粒细胞（PMN），并用流式细胞术分析细胞死亡。我们发现 ANCA 相关菌株在大多数情况下表现出绿脓素阴性表型。上皮细胞和中性粒细胞的凋亡和坏死表明，这些菌株比非 ANCA 相关菌株诱导的炎症反应更少。我们的结果表明，诱导弱炎症反应的铜绿假单胞菌菌株定植与 CF 的不良结果相关。我们推测，通过不充分的炎症反应对病原体增殖的控制不充分，会导致气道中细菌数量缓慢增加和垂死的中性粒细胞积累，从而导致 CF 肺病的进展。 (C) 2011 年欧洲囊性纤维化协会。由 Elsevier B.V. 出版。保留所有权利。
The clinical consequence of chronic Pseudomonas aeruginosa colonization in cystic fibrosis (CF) varies between individuals for unknown reasons. Auto-antibodies against bactericidal/permeability increasing protein (BPI-ANCA) are associated with poor prognosis in CF. We hypothesize that there is a correlation between the presence of BPI-ANCA, the properties of the colonizing bacteria and the clinical conditions of the host. We compared isolates of P. aeruginosa from BPI-ANCA positive CF patients who have deteriorating lung disease with BPI-ANCA negative CF patients who are in stable clinical conditions. Epithelial cells (A549) and isolated polymorphonuclear granulocytes (PMNs) were stimulated with the isolates and cell death was analyzed with flow cytometry. We found that the ANCA associated strains in most cases showed pyocyanin negative phenotypes. These strains also induced less inflammatory response than the non-ANCA associated strains as shown by apoptosis and necrosis of epithelial cells and neutrophils. Our results suggest that colonization with strains of P. aeruginosa that induce a weak inflammatory response is associated with unfavorable outcome in CF. We speculate that inadequate control of pathogen proliferation through an insufficient inflammatory response results in a slowly increasing number of bacteria and accumulation of dying PMNs in the airways, contributing to progression in CF lung disease. (C) 2011 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.