title: Nanoparticle uptake by airway phagocytes after fungal spore challenge in murine allergic asthma and chronic bronchitis.
abstract: BACKGROUND
  In healthy lungs, deposited micrometer-sized particles are efficiently phagocytosed by macrophages present on airway surfaces; however, uptake of nanoparticles (NP) by macrophages appears less effective and is largely unstudied in lung disease. Using mouse models of allergic asthma and chronic obstructive pulmonary disease (COPD), we investigated NP uptake after challenge with common biogenic ambient air microparticles.
  
  
  METHODS
  Bronchoalveolar lavage (BAL) cells from diseased mice (allergic asthma: ovalbumin [OVA] sensitized and COPD: Scnn1b-transgenic [Tg]) and their respective healthy controls were exposed ex vivo first to 3-μm fungal spores of Calvatia excipuliformis and then to 20-nm gold (Au) NP. Electron microscopic imaging was performed and NP uptake was assessed by quantitative morphometry.
  
  
  RESULTS
  Macrophages from diseased mice were significantly larger compared to controls in OVA-allergic versus sham controls and in Scnn1b-Tg versus wild type (WT) mice. The percentage of macrophages containing AuNP tended to be lower in Scnn1b-Tg than in WT mice. In all animal groups, fungal spores were localized in macrophage phagosomes, the membrane tightly surrounding the spore, whilst AuNP were found in vesicles largely exceeding NP size, co-localized in spore phagosomes and occasionally, in the cytoplasm. AuNP in vesicles were located close to the membrane. In BAL from OVA-allergic mice, 13.9 ± 8.3% of all eosinophils contained AuNP in vesicles exceeding NP size and close to the membrane.
  
  
  CONCLUSIONS
  Overall, AuNP uptake by BAL macrophages occurred mainly by co-uptake together with other material, including micrometer-sized ambient air particles like fungal spores. The lower percentage of NP containing macrophages in BAL from Scnn1b-Tg mice points to a change in the macrophage population from a highly to a less phagocytic phenotype. This likely contributes to inefficient macrophage clearance of NP in lung disease. Finally, the AuNP containing eosinophils in OVA-allergic mice show that other inflammatory cells present on airway surfaces may substantially contribute to NP uptake.
authors.affiliation: Institute of Anatomy, University of Bern, Bern, Switzerland. marianne.geiser@ana.unibe.ch.
authors.forename: Marianne
authors.initials: M
authors.lastname: Geiser
authors.forename: Christoph
authors.initials: C
authors.lastname: Wigge
authors.forename: Melanie L
authors.initials: ML
authors.lastname: Conrad
authors.forename: Sylvie
authors.initials: S
authors.lastname: Eigeldinger-Berthou
authors.forename: Lisa
authors.initials: L
authors.lastname: Künzi
authors.forename: Holger
authors.initials: H
authors.lastname: Garn
authors.forename: Harald
authors.initials: H
authors.lastname: Renz
authors.forename: Marcus A
authors.initials: MA
authors.lastname: Mall
mesh_terms: D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000503:physiopathology*; D029481:Bronchitis, Chronic / Q000235:genetics / Q000503:physiopathology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D053503:Epithelial Sodium Channels / Q000235:genetics; D005260:Female; D006046:Gold; D018655:Lymphocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D053758:Nanoparticles; D010586:Phagocytes / Q000502:physiology* / Q000648:ultrastructure*; D010587:Phagocytosis; D010588:Phagosomes / Q000648:ultrastructure; D013172:Spores, Fungal
chemical_list: D053503:Epithelial Sodium Channels; C507049:Scnn1b protein, mouse; D006046:Gold