Size-Dependent Uptake of Particles by Pulmonary Antigen-Presenting Cell Populations and Trafficking to Regional Lymph Nodes

Blank, Fabian; Stumbles, Philip A.; Seydoux, Emilie; Holt, Patrick G.; Fink, Alke; Rothen-Rutishauser, Barbara; Strickland, Deborah H.; Von Garnier, Christophe (2013). Size-Dependent Uptake of Particles by Pulmonary Antigen-Presenting Cell Populations and Trafficking to Regional Lymph Nodes. American journal of respiratory cell and molecular biology, 49(1), pp. 67-77. American Lung Association 10.1165/rcmb.2012-0387OC

Full text not available from this repository. (Request a copy)

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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Mu50 > Forschungsgruppe Pneumologie (Erwachsene)
04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Pneumology

UniBE Contributor:

Blank, Fabian; Seydoux, Emilie; Rothen-Rutishauser, Barbara and Von Garnier, Christophe

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1044-1549

Publisher:

American Lung Association

Language:

English

Submitter:

Rahel Holderegger

Date Deposited:

30 Apr 2014 08:23

Last Modified:

14 Jul 2014 17:13

Publisher DOI:

10.1165/rcmb.2012-0387OC

PubMed ID:

23492193

Uncontrolled Keywords:

nanoparticles, uptake, trafficking, dendritic cells, alveolar macrophages

URI:

https://boris.unibe.ch/id/eprint/45042

Actions (login required)

Edit item Edit item
Provide Feedback