title: In vivo effect of adhesion inhibitor heparin on Legionella pneumophila pathogenesis in a murine pneumonia model.
abstract: OBJECTIVE
  To examine the effect of intratracheal heparin instillation on Legionella pneumophila-related acute lung injury (ALI) and systemic dissemination.
  
  
  METHODS
  Prospective, controlled experimental study.
  
  
  METHODS
  University research laboratory.
  
  
  METHODS
  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.
  
  
  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.
authors: Université Lyon 1, Centre National de référence des Légionelles, Faculté de Médecine Laennec, Lyon cedex 08, France. florence.ader@univ-lyon1.fr
authors: Florence
authors: F
authors: Ader
authors: Rozenn
authors: R
authors: Le Berre
authors: Rémi
authors: R
authors: Fackeure
authors: Dominique
authors: D
authors: Raze
authors: Franco Dante
authors: FD
authors: Menozzi
authors: Nathalie
authors: N
authors: Viget
authors: Karine
authors: K
authors: Faure
authors: Eric
authors: E
authors: Kipnis
authors: Benoît
authors: B
authors: Guery
authors: Sophie
authors: S
authors: Jarraud
authors: Jerome
authors: J
authors: Etienne
authors: Christian
authors: C
authors: Chidiac
mesh_terms: D055371:Acute Lung Injury / Q000378:metabolism / Q000382:microbiology / Q000517:prevention & control*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D005343:Fibrinolytic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D006493:Heparin / Q000494:pharmacology / Q000627:therapeutic use*; D016952:Legionella pneumophila / Q000187:drug effects* / Q000472:pathogenicity; D007877:Legionnaires' Disease / Q000378:metabolism / Q000517:prevention & control*; D051379:Mice
chemical_list: D016207:Cytokines; D005343:Fibrinolytic Agents; D006493:Heparin