In vivo effect of adhesion inhibitor heparin on Legionella pneumophila pathogenesis in a murine pneumonia model

Details

Serval ID
serval:BIB_B2E5A7F3BE4D
Type
Article: article from journal or magazin.
Collection
Publications
Title
In vivo effect of adhesion inhibitor heparin on Legionella pneumophila pathogenesis in a murine pneumonia model
Journal
Intensive Care Med
Author(s)
Ader F., Le Berre R., Fackeure R., Raze D., Menozzi F. D., Viget N., Faure K., Kipnis E., Guery B., Jarraud S., Etienne J., Chidiac C.
ISSN
0342-4642 (Print)
ISSN-L
0342-4642
Publication state
Published
Issued date
08/2008
Volume
34
Number
8
Pages
1511-9
Language
english
Notes
Ader, Florence
Le Berre, Rozenn
Fackeure, Remi
Raze, Dominique
Menozzi, Franco Dante
Viget, Nathalie
Faure, Karine
Kipnis, Eric
Guery, Benoit
Jarraud, Sophie
Etienne, Jerome
Chidiac, Christian
eng
Research Support, Non-U.S. Gov't
Intensive Care Med. 2008 Aug;34(8):1511-9. doi: 10.1007/s00134-008-1063-2. Epub 2008 Mar 26.
Abstract
OBJECTIVE: To examine the effect of intratracheal heparin instillation on Legionella pneumophila-related acute lung injury (ALI) and systemic dissemination. DESIGN: Prospective, controlled experimental study. SETTING: University research laboratory. INTERVENTIONS: A/J mice received 5 microg of sulfated heparin intratracheally co-instilled with 10(6) or 10(8) colony-forming units (CFU) of a virulent isolate of L. pneumophila. MEASUREMENTS AND RESULTS: ALI was assessed in control groups (PBS and PBS-heparin) and on days 1, 2 and 3 post-infection, in terms of the lung wet-to-dry (W/D) weight ratios and of lung endothelial permeability to radio-labeled albumin (Perm-I(125)). Lung bacterial loads were measured and systemic spread was assessed by blood and target organ culture. The alveolar inflammatory response was evaluated by measuring the cytokine levels (TNF-alpha, IFN-gamma, IL-6 and IL-12p70) in bronchoalveolar lavage fluids (BALF). Co-instilled heparin improved mouse survival after the 10(8) CFU challenge (p < 0.01). On day 2, heparin co-instillation significantly reduced the W/D ratio and Perm-I(125) (p < 0.01 and p < 0.001 respectively), improved lung bacterial clearance (p < 0.001), prevented systemic dissemination (blood, liver, spleen, kidneys and brain cultures, all p < 0.05) and significantly increased IFN-gamma and IL-12p70 levels in BALF (p < 0.05). CONCLUSIONS: Heparin co-instillation during intratracheal L. pneumophila challenge has a protective effect on the alveolar-capillary barrier and prevents bacterial dissemination. These results tend to confirm the competitive inhibition by heparin of L. pneumophila attachment to lung epithelium in vivo, and point to the possible involvement of a heparan-sulfate adhesin in L. pneumophila binding to pneumocytes.
Keywords
Acute Lung Injury/metabolism/microbiology/*prevention & control, Animals, Bronchoalveolar Lavage Fluid/*chemistry, Cytokines/*metabolism, Disease Models, Animal, Female, Fibrinolytic Agents/pharmacology/*therapeutic use, Heparin/pharmacology/*therapeutic use, Legionella pneumophila/*drug effects/pathogenicity, Legionnaires' Disease/metabolism/*prevention & control, Mice
Pubmed
Create date
29/04/2021 10:59
Last modification date
30/04/2021 6:38
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