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

Delaval M, Boland S, Solhonne B, Nicola MA, Mornet S, Baeza-Squiban A, Sallenave JM, Garcia-Verdugo I - Part Fibre Toxicol (2015)

Bottom Line: 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).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.

View Article: PubMed Central - PubMed

Affiliation: 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.

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.

No MeSH data available.


Related in: MedlinePlus

Effects of silica nanoparticles in bacterial clearance. A) Mice were treated with silica NPs (SiO2) or vehicle and 5 h later infected with PAK-lux (107 CFU/mice). 15 h after infection, bioluminescence was recorded in the whole animal (panels A, B) or in extracted organs (panel C). B) Quantification of bioluminescence in the lungs. S = spleen, L = lungs. Colour scale represents photons/s/cm2/steradian. In panel A) the rib cage is delimited within the squares.
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Fig6: Effects of silica nanoparticles in bacterial clearance. A) Mice were treated with silica NPs (SiO2) or vehicle and 5 h later infected with PAK-lux (107 CFU/mice). 15 h after infection, bioluminescence was recorded in the whole animal (panels A, B) or in extracted organs (panel C). B) Quantification of bioluminescence in the lungs. S = spleen, L = lungs. Colour scale represents photons/s/cm2/steradian. In panel A) the rib cage is delimited within the squares.

Mentions: Our laboratory and others have reported that increased mortality during P. aeruginosa pneumonia could be associated with increased bacterial burden [28-30]. We therefore analysed whether SiO2 NP pre-exposure enhanced bacterial loads in the lungs of infected mice. To that aim, we studied the elimination of P.a in the whole animal using a bioluminescence approach. Mice were therefore infected with 107 CFU of a bioluminescent P.a strain (PAK-lux) as previously described [29] and 15 h later, bioluminescence was measured. We observed that NP treated mice did not present a higher bacterial load in lungs, when compared to non-treated mice (Figure 6A and B). Rather NP-treatment showed a tendency to reduce bacterial loads in lungs. To study further whether NP treatment could induce bacterial translocation, we dissected spleen and lungs to analyse associated bioluminescence. As shown in (Figure 6C), we did not detect bacterial growth in the spleen. Analysis of dissected lungs also confirmed that NP exposure did not increase bacterial loads in lungs (Figure 6C).Figure 6


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

Delaval M, Boland S, Solhonne B, Nicola MA, Mornet S, Baeza-Squiban A, Sallenave JM, Garcia-Verdugo I - Part Fibre Toxicol (2015)

Effects of silica nanoparticles in bacterial clearance. A) Mice were treated with silica NPs (SiO2) or vehicle and 5 h later infected with PAK-lux (107 CFU/mice). 15 h after infection, bioluminescence was recorded in the whole animal (panels A, B) or in extracted organs (panel C). B) Quantification of bioluminescence in the lungs. S = spleen, L = lungs. Colour scale represents photons/s/cm2/steradian. In panel A) the rib cage is delimited within the squares.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4318199&req=5

Fig6: Effects of silica nanoparticles in bacterial clearance. A) Mice were treated with silica NPs (SiO2) or vehicle and 5 h later infected with PAK-lux (107 CFU/mice). 15 h after infection, bioluminescence was recorded in the whole animal (panels A, B) or in extracted organs (panel C). B) Quantification of bioluminescence in the lungs. S = spleen, L = lungs. Colour scale represents photons/s/cm2/steradian. In panel A) the rib cage is delimited within the squares.
Mentions: Our laboratory and others have reported that increased mortality during P. aeruginosa pneumonia could be associated with increased bacterial burden [28-30]. We therefore analysed whether SiO2 NP pre-exposure enhanced bacterial loads in the lungs of infected mice. To that aim, we studied the elimination of P.a in the whole animal using a bioluminescence approach. Mice were therefore infected with 107 CFU of a bioluminescent P.a strain (PAK-lux) as previously described [29] and 15 h later, bioluminescence was measured. We observed that NP treated mice did not present a higher bacterial load in lungs, when compared to non-treated mice (Figure 6A and B). Rather NP-treatment showed a tendency to reduce bacterial loads in lungs. To study further whether NP treatment could induce bacterial translocation, we dissected spleen and lungs to analyse associated bioluminescence. As shown in (Figure 6C), we did not detect bacterial growth in the spleen. Analysis of dissected lungs also confirmed that NP exposure did not increase bacterial loads in lungs (Figure 6C).Figure 6

Bottom Line: 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).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.

View Article: PubMed Central - PubMed

Affiliation: 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.

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.

No MeSH data available.


Related in: MedlinePlus