title: M2 polarization enhances silica nanoparticle uptake by macrophages.
abstract: While silica nanoparticles have enabled numerous industrial and medical applications, their toxicological safety requires further evaluation. Macrophages are the major cell population responsible for nanoparticle clearance in vivo. The prevailing macrophage phenotype largely depends on the local immune status of the host. Whereas M1-polarized macrophages are considered as pro-inflammatory macrophages involved in host defense, M2 macrophages exhibit anti-inflammatory and wound-healing properties, but also promote tumor growth. We employed different models of M1 and M2 polarization: granulocyte-macrophage colony-stimulating factor/lipopolysaccharide (LPS)/interferon (IFN)-γ was used to generate primary human M1 cells and macrophage colony-stimulating factor (M-CSF)/interleukin (IL)-10 to differentiate M2 monocyte-derived macrophages (MDM). PMA-differentiated THP-1 cells were polarized towards an M1 type by LPS/IFN-γ and towards M2 by IL-10. Uptake of fluorescent silica nanoparticles (Ø26 and 41 nm) and microparticles (Ø1.75 μm) was quantified. At the concentration used (50 μg/ml), silica nanoparticles did not influence cell viability as assessed by MTT assay. Nanoparticle uptake was enhanced in M2-polarized primary human MDM compared with M1 cells, as shown by flow cytometric and microscopic approaches. In contrast, the uptake of microparticles did not differ between M1 and M2 phenotypes. M2 polarization was also associated with increased nanoparticle uptake in the macrophage-like THP-1 cell line. In accordance, in vivo polarized M2-like primary human tumor-associated macrophages obtained from lung tumors took up more nanoparticles than M1-like alveolar macrophages isolated from the surrounding lung tissue. In summary, our data indicate that the M2 polarization of macrophages promotes nanoparticle internalization. Therefore, the phenotypical differences between macrophage subsets should be taken into consideration in future investigations on nanosafety, but might also open up therapeutic perspectives allowing to specifically target M2 polarized macrophages.
authors: Department of Pharmacy, Pharmaceutical Biology, Saarland University, Saarbruecken Germany.
authors: Jessica
authors: J
authors: Hoppstädter
authors: Korea Institute of Science and Technology Europe, Saarbruecken Germany.
authors: Michelle
authors: M
authors: Seif
authors: Department of Pharmacy, Pharmaceutical Biology, Saarland University, Saarbruecken Germany.
authors: Anna
authors: A
authors: Dembek
authors: Nano Cell Interactions Group, INM - Leibniz Institute for New Materials, Saarbruecken Germany.
authors: Christian
authors: C
authors: Cavelius
authors: Department of Cardiothoracic Surgery, Voelklingen Heart Centre, Voelklingen Germany.
authors: Hanno
authors: H
authors: Huwer
authors: Nano Cell Interactions Group, INM - Leibniz Institute for New Materials, Saarbruecken Germany.
authors: Annette
authors: A
authors: Kraegeloh
authors: Department of Pharmacy, Pharmaceutical Biology, Saarland University, Saarbruecken Germany.
authors: Alexandra K
authors: AK
authors: Kiemer
keywords: alveolar macrophage; endocytosis; inflammation; lung macrophages; mononuclear phagocyte system; phagocytosis; real-time RT-PCR; tumor-associated macrophage