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流产子宫中 M1/M2 巨噬细胞的失衡极化。

Imbalance polarization of M1/M2 macrophages in miscarried uterus.

机构信息

Department of Obstetrics and Gynecology, The Fourth Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.

National Key Laboratory of Immunity and Inflammation, Suzhou Institute of System Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Suzhou, Jiangsu, China.

出版信息

PLoS One. 2024 Jul 25;19(7):e0304590. doi: 10.1371/journal.pone.0304590. eCollection 2024.

Abstract

BACKGROUND

Lipopolysaccharides (LPS) is well known to manifest a miscarriage-inducing effector during early pregnancy and activate macrophage to induce M1 macrophage polarization. However, the role of macrophage polarization in LPS-related miscarriage-inducing effect is not apparent.

METHODS

In this work, gene expression changes and the percentage of M1/M2 macrophages and monocytes in LPS-induced miscarried uterus were firstly analyzed by RNA sequencing (RNA-seq) and Flow Cytometry. To explore the origin that contributes to M1/M2 macrophage differentiation, the expression of monocyte chemotactic protein (MCP-1), CCL3, and CCL4, chemokines related to monocyte/macrophage migration, was tested by quantitative real time PCR (qRT-PCR).

RESULTS

We found that percentage of M1 macrophages rose, while the percentage of M2 macrophages declined down in the injected mice uterus. Meanwhile, the percentage of M1 and M2 macrophages showed no significant difference in the spleens of LPS injected mice compared to PBS injected control mice. Expression of Mcp-1, Ccl3, and Ccl4 and numbers of monocytes were remarkably up-regulated in LPS-induced miscarried mice uterus.

CONCLUSION

These results indicated that polarization and proportion changes of macrophage in the uterus may contribute to miscarriage. Our work provides new evidence correlating the aberrant regulation of M1/M2 macrophage polarization with deleterious miscarriage-inducing effects. This will help us understand the roles of critical immune cell differentiation in maintaining normal pregnancy.

摘要

背景

脂多糖(LPS)在早孕时表现出明显的流产诱导效应,激活巨噬细胞诱导 M1 巨噬细胞极化。然而,巨噬细胞极化在 LPS 相关流产诱导效应中的作用尚不清楚。

方法

在这项工作中,首先通过 RNA 测序(RNA-seq)和流式细胞术分析 LPS 诱导流产子宫中的基因表达变化和 M1/M2 巨噬细胞和单核细胞的百分比。为了探索导致 M1/M2 巨噬细胞分化的来源,通过定量实时 PCR(qRT-PCR)检测了与单核细胞/巨噬细胞迁移相关的趋化因子单核细胞趋化蛋白 1(MCP-1)、CCL3 和 CCL4 的表达。

结果

我们发现,在注射 LPS 的小鼠子宫中,M1 巨噬细胞的百分比上升,而 M2 巨噬细胞的百分比下降。同时,与注射 PBS 的对照组小鼠相比,注射 LPS 的小鼠脾脏中 M1 和 M2 巨噬细胞的百分比没有显著差异。在 LPS 诱导流产的小鼠子宫中,Mcp-1、Ccl3 和 Ccl4 的表达以及单核细胞的数量显著上调。

结论

这些结果表明,子宫中巨噬细胞的极化和比例变化可能导致流产。我们的工作提供了新的证据,表明 M1/M2 巨噬细胞极化的异常调节与有害的流产诱导效应有关。这将有助于我们理解关键免疫细胞分化在维持正常妊娠中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d10/11271943/32f6601f001a/pone.0304590.g001.jpg

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