title: Effects of copper nanoparticle exposure on host defense in a murine pulmonary infection model.
abstract: 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/m(3)) 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 × 10(5) 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.
authors.affiliation: Interdisciplinary Graduate Program in Human Toxicology, University of Iowa, Iowa City, 52242, USA.
authors.forename: Jong Sung
authors.initials: JS
authors.lastname: Kim
authors.forename: Andrea
authors.initials: A
authors.lastname: Adamcakova-Dodd
authors.forename: Patrick T
authors.initials: PT
authors.lastname: O'Shaughnessy
authors.forename: Vicki H
authors.initials: VH
authors.lastname: Grassian
authors.forename: Peter S
authors.initials: PS
authors.lastname: Thorne
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D003300:Copper / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity*; D016207:Cytokines / Q000276:immunology; D004195:Disease Models, Animal; D007113:Immunity, Innate / Q000187:drug effects*; D019570:Inhalation Exposure; D007710:Klebsiella Infections / Q000139:chemically induced / Q000276:immunology* / Q000382:microbiology; D007711:Klebsiella pneumoniae / Q000254:growth & development; D008297:Male; D053768:Metal Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration / Q000187:drug effects / Q000276:immunology; D010316:Particle Size; D018410:Pneumonia, Bacterial / Q000139:chemically induced / Q000276:immunology* / Q000382:microbiology; D013499:Surface Properties
chemical_list: D016207:Cytokines; D003300:Copper