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在 3.0T 下,用钆脂质体和超顺磁氧化铁纳米颗粒体外区分促炎和抗炎巨噬细胞。

In vitro distinction between proinflammatory and antiinflammatory macrophages with gadolinium-liposomes and ultrasmall superparamagnetic iron oxide particles at 3.0T.

机构信息

Laboratory of Imaging Biomarkers and Center for Research on Inflammation, UMR 1149 INSERM - University Paris Diderot, Sorbonne Paris Cité, Paris, France.

Department of Radiology, Beaujon University Hospital Paris Nord, Clichy, France.

出版信息

J Magn Reson Imaging. 2019 Apr;49(4):1166-1173. doi: 10.1002/jmri.26331. Epub 2018 Nov 3.

DOI:10.1002/jmri.26331
PMID:30390366
Abstract

BACKGROUND

Inflammation involves a heterogeneous macrophage population, for which there is no readily available MR assessment method.

PURPOSE

To assess the feasibility of distinguishing proinflammatory M1 and antiinflammatory M2 macrophages at MRI enhanced with gadolinium liposomes or ultrasmall superparamagnetic iron oxide particles.

STUDY TYPE

In vitro.

SPECIMEN

We employed cultured RAW macrophages. M0 macrophages were polarized with lipopolysaccharide (LPS) or interleukin-4 (IL-4), resulting in M1 or M2 macrophages. The macrophages were incubated with gadolinium (±rhodamine) liposomes or iron oxide particles and cell pellets were prepared for MRI.

FIELD STRENGTH/SEQUENCE: Transverse relaxation rates and quantitative susceptibility were obtained at 3.0T with multiecho turbo spin echo and spoiled gradient echo sequences.

ASSESSMENT

MRI results were compared with confocal microscopy, flow cytometry, and expression of endocytosis, M1 and M2 genes.

STATISTICAL TESTS

Mann-Whitney and Kruskal-Wallis tests were performed.

RESULTS

Higher transverse relaxation rates and susceptibility were observed in M1 than in M2 and M0 macrophages (P < 0.01 both with liposomes and USPIO) and significantly different susceptibility in M2 and M0 macrophages (P < 0.01 both with liposomes and USPIO). These MRI results were confirmed at confocal microscopy and flow cytometry. LPS macrophages displayed M1 gene expression, whereas IL-4 macrophages showed M2 polarization and lower endocytosis gene expression rates.

DATA CONCLUSION

These in vitro results show that it is feasible to distinguish between proinflammatory M1 and antiinflammatory M2 macrophages according to their level of contrast agent uptake at MRI.

LEVEL OF EVIDENCE

1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:1166-1173.

摘要

背景

炎症涉及异质的巨噬细胞群体,目前尚无现成的磁共振评估方法。

目的

评估磁共振增强钆脂质体或超顺磁性氧化铁颗粒对促炎 M1 和抗炎 M2 巨噬细胞的区分能力。

研究类型

体外。

标本

我们采用培养的 RAW 巨噬细胞。M0 巨噬细胞用脂多糖(LPS)或白细胞介素 4(IL-4)极化,导致 M1 或 M2 巨噬细胞。将巨噬细胞与钆(±罗丹明)脂质体或氧化铁颗粒孵育,并制备细胞沉淀进行 MRI。

磁场强度/序列:在 3.0T 上使用多回波涡轮自旋回波和扰相梯度回波序列获得横向弛豫率和定量磁化率。

评估

将 MRI 结果与共聚焦显微镜、流式细胞术以及内吞作用、M1 和 M2 基因的表达进行比较。

统计学检验

采用 Mann-Whitney 和 Kruskal-Wallis 检验。

结果

与 M2 和 M0 巨噬细胞相比,M1 巨噬细胞的横向弛豫率和磁化率更高(脂质体和 USPIO 均 P < 0.01),M2 和 M0 巨噬细胞的磁化率差异有统计学意义(脂质体和 USPIO 均 P < 0.01)。这些 MRI 结果在共聚焦显微镜和流式细胞术上得到了证实。LPS 巨噬细胞显示 M1 基因表达,而 IL-4 巨噬细胞表现出 M2 极化和较低的内吞作用基因表达率。

数据结论

这些体外结果表明,根据 MRI 对比剂摄取水平区分促炎 M1 和抗炎 M2 巨噬细胞是可行的。

证据水平

1 技术功效:阶段 1 J. Magn. Reson. Imaging 2019;49:1166-1173.

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