title: Inert 50-nm polystyrene nanoparticles that modify pulmonary dendritic cell function and inhibit allergic airway inflammation.
abstract: Nanoparticles are being developed for diverse biomedical applications, but there is concern about their potential to promote inflammation, particularly in the lung. Although a variety of ambient, anthropogenic and man-made nanoparticles can promote lung inflammation, little is known about the long-term immunomodulatory effects of inert noninflammatory nanoparticles. We previously showed polystyrene 50-nm nanoparticles coated with the neutral amino acid glycine (PS50G nanoparticles) are not inflammatory and are taken up preferentially by dendritic cells (DCs) in the periphery. We tested the effects of such nanoparticles on pulmonary DC function and the development of acute allergic airway inflammation. Surprisingly, exposure to PS50G nanoparticles did not exacerbate but instead inhibited key features of allergic airway inflammation including lung airway and parenchymal inflammation, airway epithelial mucus production, and serum allergen-specific IgE and allergen-specific Th2 cytokines in the lung-draining lymph node (LN) after allergen challenge 1 mo later. PS50G nanoparticles themselves did not induce lung oxidative stress or cardiac or lung inflammation. Mechanistically, PS50G nanoparticles did not impair peripheral allergen sensitization but exerted their effect at the lung allergen challenge phase by inhibiting expansion of CD11c(+)MHCII(hi) DCs in the lung and draining LN and allergen-laden CD11b(hi)MHCII(hi) DCs in the lung after allergen challenge. PS50G nanoparticles further suppressed the ability of CD11b(hi) DCs in the draining LN of allergen-challenged mice to induce proliferation of OVA-specific CD4(+) T cells. The discovery that a defined type of nanoparticle can inhibit, rather than promote, lung inflammation via modulation of DC function opens the door to the discovery of other nanoparticle types with exciting beneficial properties.
authors.affiliation: Department of Immunology, Monash University, Melbourne, Victoria 3004, Australia.
authors.forename: Charles L
authors.initials: CL
authors.lastname: Hardy
authors.forename: Jeanne S
authors.initials: JS
authors.lastname: LeMasurier
authors.forename: Gabrielle T
authors.initials: GT
authors.lastname: Belz
authors.forename: Karen
authors.initials: K
authors.lastname: Scalzo-Inguanti
authors.forename: Jun
authors.initials: J
authors.lastname: Yao
authors.forename: Sue D
authors.initials: SD
authors.lastname: Xiang
authors.forename: Peter
authors.initials: P
authors.lastname: Kanellakis
authors.forename: Alex
authors.initials: A
authors.lastname: Bobik
authors.forename: Deborah H
authors.initials: DH
authors.lastname: Strickland
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Rolland
authors.forename: Robyn E
authors.initials: RE
authors.lastname: O'Hehir
authors.forename: Magdalena
authors.initials: M
authors.lastname: Plebanski
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D008168:Lung / Q000276:immunology; D051379:Mice; D049329:Nanostructures / Q000627:therapeutic use*; D018384:Oxidative Stress; D011014:Pneumonia / Q000188:drug therapy / Q000517:prevention & control*; D011137:Polystyrenes / Q000627:therapeutic use*
chemical_list: D011137:Polystyrenes