Authors:
Blank F, Stumbles PA, Seydoux E, Holt PG, Fink A, Rothen-Rutishauser B, Strickland DH, von Garnier C
Authors notes:
American Journal of Respiratory Cell and Molecular Biology. 2013;49(1):67-77
Keywords:
Nanoparticles, uptake, trafficking, dendritic cells, alveolar macrophages
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.
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 CD31 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 CD41 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 con- fined 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.