Details:

Alternative Title:
Part Fibre Toxicol
Personal Author:
Kim, Jong Sung ; Adamcakova-Dodd, Andrea ; O'Shaughnessy, Patrick T ; Grassian, Vicki H ; Thorne, Peter S
Kim, Jong Sung ; Adamcakova-Dodd, Andrea ; O'Shaughnessy, Patrick T ; Grassian, Vicki H ; Thorne, Peter S Less -
Description:
Background

Human exposure to nanoparticles (NPs) and environmental bacteria can occur simultaneously. NPs induce inflammatory responses and oxidative stress but may also have immune-suppressive effects, impairing macrophage function and altering epithelial barrier functions. The purpose of this study was to assess the potential pulmonary effects of inhalation and instillation exposure to copper (Cu) NPs using a model of lung inflammation and host defense.

Methods

We used Klebsiella pneumoniae (K.p.) in a murine lung infection model to determine if pulmonary bacterial clearance is enhanced or impaired by Cu NP exposure. Two different exposure modes were tested: sub-acute inhalation (4 hr/day, 5 d/week for 2 weeks, 3.5 mg/m3) and intratracheal instillation (24 hr post-exposure, 3, 35, and 100 μg/mouse). Pulmonary responses were evaluated by lung histopathology plus measurement of differential cell counts, total protein, lactate dehydrogenase (LDH) activity, and inflammatory cytokines in bronchoalveolar lavage (BAL) fluid.

Results

Cu NP exposure induced inflammatory responses with increased recruitment of total cells and neutrophils to the lungs as well as increased total protein and LDH activity in BAL fluid. Both inhalation and instillation exposure to Cu NPs significantly decreased the pulmonary clearance of K.p.-exposed mice measured 24 hr after bacterial infection following Cu NP exposure versus sham-exposed mice also challenged with K.p (1.4 × 105 bacteria/mouse).

Conclusions

Cu NP exposure impaired host defense against bacterial lung infections and induced a dose-dependent decrease in bacterial clearance in which even our lowest dose demonstrated significantly lower clearance than observed in sham-exposed mice. Thus, exposure to Cu NPs may increase the risk of pulmonary infection.


Subjects:
[+]
Animals Bacterial Clearance Bronchoalveolar Lavage Fluid Copper Cytokines Disease Models, Animal Immunity, Innate Inhalation Inhalation Exposure Instillation Klebsiella Infections Klebsiella Pneumoniae Male Metal Nanoparticles Mice Mice, Inbred C57BL Murine Nanoparticles Neutrophil Infiltration Particle Size Pneumonia, Bacterial Pulmonary Infection Research Surface Properties
Source:
Part Fibre Toxicol. 2011; 8:29.
Pubmed ID:
21943386
Pubmed Central ID:
PMC3193802
Document Type:
Journal Article
Funding:
P30 ES005605/ES/NIEHS NIH HHS/United States ; R01 OH009448/OH/NIOSH CDC HHS/United States
P30 ES005605/ES/NIEHS NIH HHS/United States ; R01 OH009448/OH/NIOSH CDC HHS/United States Less -
Collection(s):
CDC Public Access
Main Document Checksum:
[+]
urn:sha256:74f9f51068680bff4027db551039d3eb324fcdb95a393187a4d622a247395c52
Download URL:
https://stacks.cdc.gov/view/cdc/22779/cdc_22779_DS1.pdf
File Type:

Supporting Files

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