M2 polarization enhances silica nanoparticle uptake by macrophages.
M2 polarization enhances silica nanoparticle uptake by macrophages.
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DOI：
10.3389/fphar.2015.00055
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发表时间：
2015
影响因子：
5.6
通讯作者：
Kiemer AK
中科院分区：
文献类型：
--
作者：
Hoppstädter J;Seif M;Dembek A;Cavelius C;Huwer H;Kraegeloh A;Kiemer AK
虽然二氧化硅纳米颗粒已经实现了许多工业和医疗应用，但其毒理学安全性需要进一步评估。巨噬细胞是负责体内纳米颗粒清除的主要细胞群。主要的巨噬细胞表型很大程度上取决于宿主的局部免疫状态。M1极化巨噬细胞被认为是参与宿主防御的促炎巨噬细胞，而M2巨噬细胞表现出抗炎和伤口愈合特性，但也促进肿瘤生长。我们采用不同的M1和M2极化模型：用粒细胞-巨噬细胞集落刺激因子/脂多糖（LPS）/干扰素（IFN）-γ诱导原代人M1细胞，用巨噬细胞集落刺激因子（M-CSF）/白细胞介素（IL）-10诱导M2单核细胞源性巨噬细胞（MDM）分化。PMA分化的THP-1细胞通过LPS/IFN-γ向M1型极化，通过IL-10向M2型极化。对荧光二氧化硅纳米颗粒（1.26和41 nm）和微粒（1.75 μm）的摄取进行定量。在使用的浓度（50 μg/ml）下，如通过MTT测定所评估的，二氧化硅纳米颗粒不影响细胞活力。如流式细胞术和显微镜方法所示，与M1细胞相比，M2极化的原代人MDM中的纳米颗粒摄取增强。相比之下，微粒的摄取在M1和M2表型之间没有差异。M2极化也与巨噬细胞样THP-1细胞系中纳米颗粒摄取增加相关。因此，从肺肿瘤中获得的体内极化的M2样原代人肿瘤相关巨噬细胞比从周围肺组织中分离的M1样肺泡巨噬细胞吸收更多的纳米颗粒。总之，我们的数据表明巨噬细胞的M2极化促进纳米颗粒内化。因此，在未来的纳米安全性研究中应考虑巨噬细胞亚群之间的表型差异，但也可能开辟允许特异性靶向M2极化巨噬细胞的治疗前景。
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.
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影响因子：
10
作者：
Klein SG;Serchi T;Hoffmann L;Blömeke B;Gutleb AC
通讯作者：
Gutleb AC
影响因子：
5.4
作者：
Hoppstaedter, Jessica;Diesel, Britta;Kiemer, Alexandra K.
通讯作者：
Kiemer, Alexandra K.
影响因子：
9.7
作者：
Astanina, Ksenia;Simon, Yvette;Kiemer, Alexandra K.
通讯作者：
Kiemer, Alexandra K.
影响因子：
3.7
作者：
Autengruber, Andrea;Sydlik, Ulrich;Unfried, Klaus
通讯作者：
Unfried, Klaus
影响因子：
38.3
作者：
Deng, Zhou J.;Liang, Mingtao;Minchin, Rodney F.
通讯作者：
Minchin, Rodney F.