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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

Survival curves of mice infected withPseudomonas aeruginosastrain PAK. C57Bl/6j mice were instilled with 5 mg/kg (100 μg/mice) of SiO2 NPs or vehicle. 5 h after, mice were infected with P. aeruginosa (PAK strain) (2x107 CFU/mice) and survival was followed over time. (*) p < 0.05 Log-Rank (Mantel-Cox) test (n = 10 mice per group).
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Fig5: Survival curves of mice infected withPseudomonas aeruginosastrain PAK. C57Bl/6j mice were instilled with 5 mg/kg (100 μg/mice) of SiO2 NPs or vehicle. 5 h after, mice were infected with P. aeruginosa (PAK strain) (2x107 CFU/mice) and survival was followed over time. (*) p < 0.05 Log-Rank (Mantel-Cox) test (n = 10 mice per group).

Mentions: Considering that SiO2 NPs interact with AM and AEC, two cell types driving lung defence against P.a, we studied the consequences of NP exposure in a mouse model of P.a infection. First we studied the effect of NP exposure on P.a-induced mortality in mice. Intranasal administration of 2x107 CFU per mice killed almost 40% of mice 72 h post infection (Figure 5). Crucially, pre-exposure to SiO2 NPs 5 h before bacterial challenge enhanced mouse mortality by 20%, indicating a deleterious effect of NP exposure in our mice model of acute pneumonia.Figure 5


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)

Survival curves of mice infected withPseudomonas aeruginosastrain PAK. C57Bl/6j mice were instilled with 5 mg/kg (100 μg/mice) of SiO2 NPs or vehicle. 5 h after, mice were infected with P. aeruginosa (PAK strain) (2x107 CFU/mice) and survival was followed over time. (*) p < 0.05 Log-Rank (Mantel-Cox) test (n = 10 mice per group).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig5: Survival curves of mice infected withPseudomonas aeruginosastrain PAK. C57Bl/6j mice were instilled with 5 mg/kg (100 μg/mice) of SiO2 NPs or vehicle. 5 h after, mice were infected with P. aeruginosa (PAK strain) (2x107 CFU/mice) and survival was followed over time. (*) p < 0.05 Log-Rank (Mantel-Cox) test (n = 10 mice per group).
Mentions: Considering that SiO2 NPs interact with AM and AEC, two cell types driving lung defence against P.a, we studied the consequences of NP exposure in a mouse model of P.a infection. First we studied the effect of NP exposure on P.a-induced mortality in mice. Intranasal administration of 2x107 CFU per mice killed almost 40% of mice 72 h post infection (Figure 5). Crucially, pre-exposure to SiO2 NPs 5 h before bacterial challenge enhanced mouse mortality by 20%, indicating a deleterious effect of NP exposure in our mice model of acute pneumonia.Figure 5

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