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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 NPs in alveolar-capillary permeability. C57Bl/6j mice were instilled with 5 mg/kg (100 μg/mice) of SiO2 NPs, FITC- SiO2 NPs or vehicle. 5 h or 24 h later, mice were sacrificed and IgM (A) and sVCAM-1 (B) concentrations in BALs (2 ml) were measured by sandwich ELISA. Mean ± SEM is represented from 5 mice per group *p < 0.05 vs. Vehicle, Mann–Whitney test.
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Fig4: Effects of silica NPs in alveolar-capillary permeability. C57Bl/6j mice were instilled with 5 mg/kg (100 μg/mice) of SiO2 NPs, FITC- SiO2 NPs or vehicle. 5 h or 24 h later, mice were sacrificed and IgM (A) and sVCAM-1 (B) concentrations in BALs (2 ml) were measured by sandwich ELISA. Mean ± SEM is represented from 5 mice per group *p < 0.05 vs. Vehicle, Mann–Whitney test.

Mentions: Because SiO2 NPs associated with AEC (Figure 3), and as AECs guarantee epithelial barrier integrity [25], we wondered whether SiO2 NPs could alter the alveolar-capillary barrier integrity. This was assessed by measuring IgM (a pentameric serum protein with a Mr 900 kDa) concentration in BAL fluids. Increased amounts of IgM in BAL fluids are related with alterations in alveolar-capillary barrier and increased lung permeability as previously described [24,26,27]. As show Figure 4A, SiO2 NP instillation increased the concentration of IgM in BALs 24 h post treatment. Interestingly, at this time point, levels of soluble vascular cell adhesion molecule-1 (sVCAM-1) in BALs, a parameter related to endothelium injury and activation, was not modified (Figure 4B). These data indicate that SiO2 NPs increase alveolar-capillary barrier with minor alterations of the vascular endothelium.Figure 4


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 NPs in alveolar-capillary permeability. C57Bl/6j mice were instilled with 5 mg/kg (100 μg/mice) of SiO2 NPs, FITC- SiO2 NPs or vehicle. 5 h or 24 h later, mice were sacrificed and IgM (A) and sVCAM-1 (B) concentrations in BALs (2 ml) were measured by sandwich ELISA. Mean ± SEM is represented from 5 mice per group *p < 0.05 vs. Vehicle, Mann–Whitney test.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig4: Effects of silica NPs in alveolar-capillary permeability. C57Bl/6j mice were instilled with 5 mg/kg (100 μg/mice) of SiO2 NPs, FITC- SiO2 NPs or vehicle. 5 h or 24 h later, mice were sacrificed and IgM (A) and sVCAM-1 (B) concentrations in BALs (2 ml) were measured by sandwich ELISA. Mean ± SEM is represented from 5 mice per group *p < 0.05 vs. Vehicle, Mann–Whitney test.
Mentions: Because SiO2 NPs associated with AEC (Figure 3), and as AECs guarantee epithelial barrier integrity [25], we wondered whether SiO2 NPs could alter the alveolar-capillary barrier integrity. This was assessed by measuring IgM (a pentameric serum protein with a Mr 900 kDa) concentration in BAL fluids. Increased amounts of IgM in BAL fluids are related with alterations in alveolar-capillary barrier and increased lung permeability as previously described [24,26,27]. As show Figure 4A, SiO2 NP instillation increased the concentration of IgM in BALs 24 h post treatment. Interestingly, at this time point, levels of soluble vascular cell adhesion molecule-1 (sVCAM-1) in BALs, a parameter related to endothelium injury and activation, was not modified (Figure 4B). These data indicate that SiO2 NPs increase alveolar-capillary barrier with minor alterations of the vascular endothelium.Figure 4

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