title: Size-dependent uptake of particles by pulmonary antigen-presenting cell populations and trafficking to regional lymph nodes.
abstract: The respiratory tract is an attractive target organ for novel diagnostic and therapeutic applications with nano-sized carriers, but their immune effects and interactions with key resident antigen-presenting cells (APCs) such as dendritic cells (DCs) and alveolar macrophages (AMs) in different anatomical compartments remain poorly understood. Polystyrene particles ranging from 20 nm to 1,000 nm were instilled intranasally in BALB/c mice, and their interactions with APC populations in airways, lung parenchyma, and lung-draining lymph nodes (LDLNs) were examined after 2 and 24 hours by flow cytometry and confocal microscopy. In the main conducting airways and lung parenchyma, DC subpopulations preferentially captured 20-nm particles, compared with 1,000-nm particles that were transported to the LDLNs by migratory CD11blow DCs and that were observed in close proximity to CD3⁺ T cells. Generally, the uptake of particles increased the expression of CD40 and CD86 in all DC populations, independent of particle size, whereas 20-nm particles induced enhanced antigen presentation to CD4⁺ T cells in LDLNs in vivo. Despite measurable uptake by DCs, the majority of particles were taken up by AMs, irrespective of size. Confocal microscopy and FACS analysis showed few particles in the main conducting airways, but a homogeneous distribution of all particle sizes was evident in the lung parenchyma, mostly confined to AMs. Particulate size as a key parameter determining uptake and trafficking therefore determines the fate of inhaled particulates, and this may have important consequences in the development of novel carriers for pulmonary diagnostic or therapeutic applications.
authors.affiliation: Department of Respiratory Medicine, Bern University Hospital, Bern, Switzerland. fabian.blank@dkf.unibe.ch
authors.forename: Fabian
authors.initials: F
authors.lastname: Blank
authors.forename: Philip A
authors.initials: PA
authors.lastname: Stumbles
authors.forename: Emilie
authors.initials: E
authors.lastname: Seydoux
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Holt
authors.forename: Alke
authors.initials: A
authors.lastname: Fink
authors.forename: Barbara
authors.initials: B
authors.lastname: Rothen-Rutishauser
authors.forename: Deborah H
authors.initials: DH
authors.lastname: Strickland
authors.forename: Christophe
authors.initials: C
authors.lastname: von Garnier
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology*; D039481:CD11b Antigen / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D019013:CD40 Antigens / Q000276:immunology; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D008168:Lung / Q000276:immunology / Q000473:pathology; D008198:Lymph Nodes / Q000276:immunology*; D016676:Macrophages, Alveolar / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D010047:Ovalbumin / Q000276:immunology; D010316:Particle Size; D011137:Polystyrenes / Q000008:administration & dosage / Q000276:immunology; D013997:Time Factors
chemical_list: D039481:CD11b Antigen; D019013:CD40 Antigens; D011137:Polystyrenes; D010047:Ovalbumin