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Part Fibre Toxicol. 2015 Jan 21;12:1. doi: 10.1186/s12989-014-0078-9.

Acute exposure to silica nanoparticles enhances mortality and increases lung permeability in a mouse model of Pseudomonas aeruginosa pneumonia.

Author information

1
Univ Paris Diderot. Sorbone Paris Cité. Unit of Functional and Adaptive Biology (BFA) UMR 8251, CNRS, Laboratory of Molecular and Cellular Responses to Xenobiotics, 5 rue Thomas Mann, 75013, Paris, France. mathilde.delaval@gmail.com.
2
Univ Paris Diderot. Sorbone Paris Cité. Unit of Functional and Adaptive Biology (BFA) UMR 8251, CNRS, Laboratory of Molecular and Cellular Responses to Xenobiotics, 5 rue Thomas Mann, 75013, Paris, France. boland@univ-paris-diderot.fr.
3
Unité de Défense Innée et Inflammation, Institut Pasteur, 25 rue du Dr Roux, 75015, Paris, France. brigitte.solhonne@inserm.fr.
4
INSERM U874, Institut Pasteur, 25 rue du Dr Roux, 75015, Paris, France. brigitte.solhonne@inserm.fr.
5
INSERM U1152, Faculté de Médicine site Bichat, Université Paris Diderot, 16, rue Henri Huchard, 75018, Paris, France. brigitte.solhonne@inserm.fr.
6
Plateforme d'imagerie dynamique, Institut Pasteur, 25 rue du Dr Roux, 75015, Paris, France. manicola@pasteur.fr.
7
CNRS, Univ. Bordeaux, ICMCB, UPR 9048, 87 Avenue du Docteur A. Schweitzer, Pessac cedex, F-33600, France. mornet@icmcb-bordeaux.cnrs.fr.
8
Univ Paris Diderot. Sorbone Paris Cité. Unit of Functional and Adaptive Biology (BFA) UMR 8251, CNRS, Laboratory of Molecular and Cellular Responses to Xenobiotics, 5 rue Thomas Mann, 75013, Paris, France. baeza@univ-paris-diderot.fr.
9
Unité de Défense Innée et Inflammation, Institut Pasteur, 25 rue du Dr Roux, 75015, Paris, France. jean-michel.sallenave@inserm.fr.
10
INSERM U874, Institut Pasteur, 25 rue du Dr Roux, 75015, Paris, France. jean-michel.sallenave@inserm.fr.
11
INSERM U1152, Faculté de Médicine site Bichat, Université Paris Diderot, 16, rue Henri Huchard, 75018, Paris, France. jean-michel.sallenave@inserm.fr.
12
Université Sorbonne Paris Cité, Cellule Pasteur, Université Paris Diderot, rue du Dr Roux, 75015, Paris, France. jean-michel.sallenave@inserm.fr.
13
Unité de Défense Innée et Inflammation, Institut Pasteur, 25 rue du Dr Roux, 75015, Paris, France. ignacio.garcia-verdugo@inserm.fr.
14
INSERM U874, Institut Pasteur, 25 rue du Dr Roux, 75015, Paris, France. ignacio.garcia-verdugo@inserm.fr.
15
INSERM U1152, Faculté de Médicine site Bichat, Université Paris Diderot, 16, rue Henri Huchard, 75018, Paris, France. ignacio.garcia-verdugo@inserm.fr.
16
Université Sorbonne Paris Cité, Cellule Pasteur, Université Paris Diderot, rue du Dr Roux, 75015, Paris, France. ignacio.garcia-verdugo@inserm.fr.

Abstract

BACKGROUND:

The lung epithelium constitutes the first barrier against invading pathogens and also a major surface potentially exposed to nanoparticles. In order to ensure and preserve lung epithelial barrier function, the alveolar compartment possesses local defence mechanisms that are able to control bacterial infection. For instance, alveolar macrophages are professional phagocytic cells that engulf bacteria and environmental contaminants (including nanoparticles) and secrete pro-inflammatory cytokines to effectively eliminate the invading bacteria/contaminants. The consequences of nanoparticle exposure in the context of lung infection have not been studied in detail. Previous reports have shown that sequential lung exposure to nanoparticles and bacteria may impair bacterial clearance resulting in increased lung bacterial loads, associated with a reduction in the phagocytic capacity of alveolar macrophages.

RESULTS:

Here we have studied the consequences of SiO2 nanoparticle exposure on Pseudomonas aeruginosa clearance, Pseudomonas aeruginosa-induced inflammation and lung injury in a mouse model of acute pneumonia. We observed that pre-exposure to SiO2 nanoparticles increased mice susceptibility to lethal pneumonia but did not modify lung clearance of a bioluminescent Pseudomonas aeruginosa strain. Furthermore, internalisation of SiO2 nanoparticles by primary alveolar macrophages did not reduce the capacity of the cells to clear Pseudomonas aeruginosa. In our murine model, SiO2 nanoparticle pre-exposure preferentially enhanced Pseudomonas aeruginosa-induced lung permeability (the latter assessed by the measurement of alveolar albumin and IgM concentrations) rather than contributing to Pseudomonas aeruginosa-induced lung inflammation (as measured by leukocyte recruitment and cytokine concentration in the alveolar compartment).

CONCLUSIONS:

We show that pre-exposure to SiO2 nanoparticles increases mice susceptibility to lethal pneumonia but independently of macrophage phagocytic function. The deleterious effects of SiO2 nanoparticle exposure during Pseudomonas aeruginosa-induced pneumonia are related to alterations of the alveolar-capillary barrier rather than to modulation of the inflammatory responses.

PMID:
25605549
PMCID:
PMC4318199
DOI:
10.1186/s12989-014-0078-9
[Indexed for MEDLINE]
Free PMC Article

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