VEGF may contribute to macrophage recruitment and M2 polarization in the decidua.
VEGF may contribute to macrophage recruitment and M2 polarization in the decidua.
复制标题
DOI：
10.1371/journal.pone.0191040
复制
发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Nayak NR
中科院分区：
文献类型：
--
作者：
Wheeler KC;Jena MK;Pradhan BS;Nayak N;Das S;Hsu CD;Wheeler DS;Chen K;Nayak NR
越来越多的证据表明，蜕膜中产生的细胞因子和生长因子在局部免疫微环境的调节和妊娠的建立中起着关键作用。在蜕膜中产生的主要生长因子之一是血管内皮生长因子（VEGF），其不仅作用于内皮细胞，而且作用于多种其他细胞类型，包括巨噬细胞。我们试图确定是否蜕膜来源的VEGF影响巨噬细胞的募集和极化使用人子宫内膜/蜕膜组织样本，原代人子宫内膜基质细胞（ESC），和人单核细胞系THP 1。原位杂交用于评估局部VEGF表达，免疫组化用于鉴定和定位CD 68阳性的子宫内膜巨噬细胞。使用transwell迁移试验评估培养物中的巨噬细胞迁移，并使用定量实时PCR（qRT-PCR）评估各种M1/M2表型标志物和VEGF表达。我们发现，与分泌期子宫内膜（非妊娠）相比，妊娠早期蜕膜中VEGF水平和巨噬细胞数量均显著增加，M2巨噬细胞标志物显著增加，表明M2是蜕膜中主要的巨噬细胞表型。然而，先兆子痫妊娠的蜕膜样本显示巨噬细胞表型标记物的显著变化，M1标记物上调，M2标记物下调。在THP 1培养物中，VEGF处理显著增强巨噬细胞迁移并诱导M1巨噬细胞转变为M2表型。此外，蜕膜化ESC的条件培养基治疗诱导巨噬细胞迁移和极化的变化类似于VEGF治疗。这些作用通过加入有效的VEGF抑制剂而消除。总之，这些结果表明，蜕膜VEGF在巨噬细胞募集和M2极化中起着重要作用，并且VEGF信号传导的抑制可能有助于在不同的妊娠疾病（包括先兆子痫）中观察到的巨噬细胞极性的转变。
It is increasingly evident that cytokines and growth factors produced in the decidua play a pivotal role in the regulation of the local immune microenvironment and the establishment of pregnancy. One of the major growth factors produced in the decidua is vascular endothelial growth factor (VEGF), which acts not only on endothelial cells, but also on multiple other cell types, including macrophages. We sought to determine whether decidua-derived VEGF affects macrophage recruitment and polarization using human endometrial/decidual tissue samples, primary human endometrial stromal cells (ESCs), and the human monocyte cell line THP1. In situ hybridization was used for assessment of local VEGF expression and immunohistochemistry was used for identification and localization of CD68-positive endometrial macrophages. Macrophage migration in culture was assessed using a transwell migration assay, and the various M1/M2 phenotypic markers and VEGF expression were assessed using quantitative real-time PCR (qRT-PCR). We found dramatic increases in both VEGF levels and macrophage numbers in the decidua during early pregnancy compared to the secretory phase endometrium (non-pregnant), with a significant increase in M2 macrophage markers, suggesting that M2 is the predominant macrophage phenotype in the decidua. However, decidual samples from preeclamptic pregnancies showed a significant shift in macrophage phenotype markers, with upregulation of M1 and downregulation of M2 markers. In THP1 cultures, VEGF treatment significantly enhanced macrophage migration and induced M1 macrophages to shift to an M2 phenotype. Moreover, treatment with conditioned media from decidualized ESCs induced changes in macrophage migration and polarization similar to that of VEGF treatment. These effects were abrogated by the addition of a potent VEGF inhibitor. Together these results suggest that decidual VEGF plays a significant role in macrophage recruitment and M2 polarization, and that inhibition of VEGF signaling may contribute to the shift in macrophage polarity observed in different pregnancy disorders, including preeclampsia.
登录
查看更多内容
影响因子：
--
作者：
Douglas NC;Zimmermann RC;Tan QK;Sullivan-Pyke CS;Sauer MV;Kitajewski JK;Shawber CJ
通讯作者：
Shawber CJ
影响因子：
7.3
作者：
Faas MM;Spaans F;De Vos P
通讯作者：
De Vos P
影响因子：
5.3
作者：
Czepluch, Frauke S.;Olieslagers, Serve;Waltenberger, Johannes
通讯作者：
Waltenberger, Johannes
影响因子：
4.8
作者：
Hannan, N. J.;Paiva, P.;Salamonsen, L. A.
通讯作者：
Salamonsen, L. A.
影响因子：
3.6
作者：
Hess, A. P.;Hamilton, A. E.;Giudice, L. C.
通讯作者：
Giudice, L. C.