Journal
JOURNAL OF CYSTIC FIBROSIS
Volume 10, Issue 4, Pages 265-271Publisher
ELSEVIER
DOI: 10.1016/j.jcf.2011.03.004
Keywords
BPI-ANCA; Pseudomonas aeruginosa; Chronic colonization; Neutrophils; Pyocyanin; Interleukin 8; Anti-neutrophil cytoplasmic antibodies; Apoptosis
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Funding
- Bengt Andreasson's foundation
- Swedish Heart and Lund Foundation (Hjartlungfonden)
- Swedish CF Association
- Crafoord foundation
- Swedish Research council [K2009-65x-15152-06-3]
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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.
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