251901 Effects of Copper Nanoparticle Exposure on Host Defense in a Murine Pulmonary Infection Model

Monday, October 31, 2011

Jong Sung Kim , Human Toxicology (Department of Occupational & Environmental Health), The University of Iowa, Iowa City, IA
Andrea Adamcakova-Dodd , Department of Occupational & Environmental Health, The University of Iowa, Iowa City, IA
Patrick T. O'Shaughnessy , Department of Occupational & Environmental Health, The University of Iowa, Iowa City, IA
Vicki H. Grassian , Departments of Chemistry, The University of Iowa, Iowa City, IA
Peter Thorne , Department of Occupational & Environmental Health, The University of Iowa, Iowa City, IA
Background: Human exposure to nanoparticles (NPs) and pathogenic 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 (sub-acute inhalation and intratracheal instillation). 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 x 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.

Student participated in the study design, conducted animal exposure studies, data analysis, and drafted the manuscript.

Learning Areas:
Public health or related research

Learning Objectives:
Determine the pulmonary effects of inhalation and instillation exposure to copper nanoparticles. Describe the effects of copper nanoparticle exposure on host defense against bacterial infection. Assess interactions with copper nanoparticles and microbial infections. Become aware that exposure to Cu NPs may increase the risk of pulmonary infection.

Presenting author's disclosure statement:

Qualified on the content I am responsible for because: I am a member of Delta Omega.
Any relevant financial relationships? No

I agree to comply with the American Public Health Association Conflict of Interest and Commercial Support Guidelines, and to disclose to the participants any off-label or experimental uses of a commercial product or service discussed in my presentation.