Effects of copper nanoparticle exposure on host defense in a murine pulmonary infection model

Jong Sung Kim; Andrea Adamcakova-Dodd; Patrick T O'Shaughnessy; Vicki H Grassian; Peter S Thorne

doi:10.1186/1743-8977-8-29

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Effects of copper nanoparticle exposure on host defense in a murine pulmonary infection model

Journal article

Open access

Peer reviewed

Effects of copper nanoparticle exposure on host defense in a murine pulmonary infection model

Jong Sung Kim, Andrea Adamcakova-Dodd, Patrick T O'Shaughnessy, Vicki H Grassian and Peter S Thorne

Particle and fibre toxicology, Vol.8(1), pp.29-29

2011

DOI: 10.1186/1743-8977-8-29

PMCID: PMC3193802

PMID: 21943386

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Abstract

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.

murine

inhalation

pulmonary infection

nanoparticles

instillation

bacterial clearance

Research

Copper

Klebsiella pneumoniae

Details

Title: Subtitle: Effects of copper nanoparticle exposure on host defense in a murine pulmonary infection model
Creators: Jong Sung Kim - Department of Chemistry, University of Iowa, Iowa City, IA 52242, USA
Andrea Adamcakova-Dodd - Department of Chemistry, University of Iowa, Iowa City, IA 52242, USA
Patrick T O'Shaughnessy - Department of Chemistry, University of Iowa, Iowa City, IA 52242, USA
Vicki H Grassian - Department of Chemistry, University of Iowa, Iowa City, IA 52242, USA
Peter S Thorne - Department of Chemistry, University of Iowa, Iowa City, IA 52242, USA
Resource Type: Journal article
Publication Details: Particle and fibre toxicology, Vol.8(1), pp.29-29
DOI: 10.1186/1743-8977-8-29
PMID: 21943386
PMCID: PMC3193802
NLM abbreviation: Part Fibre Toxicol
ISSN: 1743-8977
eISSN: 1743-8977
Publisher: BioMed Central
Language: English
Date published: 2011
Academic Unit: Civil and Environmental Engineering; Occupational and Environmental Health; Stead Family Department of Pediatrics; Chemistry; Chemical and Biochemical Engineering
Record Identifier: 9983997315502771

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