Document Detail


Bead-size directed distribution of Pseudomonas aeruginosa results in distinct inflammatory response in a mouse model of chronic lung infection.
MedLine Citation:
PMID:  23039893     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Chronic Pseudomonas aeruginosa lung infection in cystic fibrosis (CF) patients is characterized by biofilms, tolerant to antibiotics and host responses. Instead, immune responses contribute to the tissue damage. However, this may depend on localization of infection in the upper conductive or in the peripheral respiratory zone. To study this we produced two distinct sizes of small alginate beads (SB) and large beads (LB) containing P. aeruginosa. In total, 175 BALB/c mice were infected with either SB or LB. At day 1 the quantitative bacteriology was higher in the SB group compared to the LB group (P < 0·003). For all time-points smaller biofilms were identified by Alcian blue staining in the SB group (P < 0·003). Similarly, the area of the airways in which biofilms were identified were smaller (P < 0·0001). A shift from exclusively endobronchial to both parenchymal and endobronchial localization of inflammation from day 1 to days 2/3 (P < 0·05), as well as a faster resolution of inflammation at days 5/6, was observed in the SB group (P < 0·03). Finally, both the polymorphonuclear neutrophil leucocyte (PMN) mobilizer granulocyte colony-stimulating factor (G-CSF) and chemoattractant macrophage inflammatory protein-2 (MIP-2) were increased at day 1 in the SB group (P < 0·0001). In conclusion, we have established a model enabling studies of host responses in different pulmonary zones. An effective recognition of and a more pronounced host response to infection in the peripheral zones, indicating that increased lung damage was demonstrated. Therefore, treatment of the chronic P. aeruginosa lung infection should be directed primarily at the peripheral lung zone by combined intravenous and inhalation antibiotic treatment.
Authors:
L J Christophersen; H Trøstrup; D S Malling Damlund; T Bjarnsholt; K Thomsen; P Ø Jensen; H P Hougen; N Høiby; C Moser
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Clinical and experimental immunology     Volume:  170     ISSN:  1365-2249     ISO Abbreviation:  Clin. Exp. Immunol.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-10-08     Completed Date:  2013-03-18     Revised Date:  2013-11-05    
Medline Journal Info:
Nlm Unique ID:  0057202     Medline TA:  Clin Exp Immunol     Country:  England    
Other Details:
Languages:  eng     Pagination:  222-30     Citation Subset:  IM    
Copyright Information:
© 2012 British Society for Immunology.
Affiliation:
Department of Clinical Microbiology 93.01, Copenhagen University Hospital, Rigshospitalet Department of Forensic Medicine, University of Copenhagen, Copenhagen, Denmark.
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MeSH Terms
Descriptor/Qualifier:
Alginates
Animals
Biofilms
Chemokine CXCL2 / immunology
Chronic Disease
Cystic Fibrosis / immunology,  microbiology
Female
Glucuronic Acid / immunology
Granulocyte Colony-Stimulating Factor / immunology
Hexuronic Acids / immunology
Inflammation / immunology,  microbiology
Lung / immunology,  microbiology
Lung Diseases / immunology*,  microbiology*
Mice
Mice, Inbred BALB C
Neutrophils / immunology
Pseudomonas Infections / immunology*,  microbiology*
Pseudomonas aeruginosa / immunology*
Respiratory Tract Infections / immunology
Chemical
Reg. No./Substance:
0/Alginates; 0/Chemokine CXCL2; 0/Cxcl2 protein, mouse; 0/Hexuronic Acids; 143011-72-7/Granulocyte Colony-Stimulating Factor; 576-37-4/Glucuronic Acid; 9005-32-7/alginic acid
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