Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U. S. Department of Health and Human Services, Bethesda, Maryland, and Detroit, Michigan.
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, Michigan.
Am J Reprod Immunol. 2019 Apr;81(4):e13098. doi: 10.1111/aji.13098. Epub 2019 Mar 4.
Acute atherosis is a uteroplacental arterial lesion that is associated with pregnancy complications such as preeclampsia and preterm birth, the latter being the leading cause of perinatal morbidity and mortality worldwide. However, the immunobiology of acute atherosis is poorly understood.
Placental basal plate samples were collected from women who delivered with (n = 11) and without (n = 31) decidua basalis lesions of acute atherosis. Multicolor flow cytometry was used to quantify M1- and M2-like macrophage subsets and the expression of iNOS and IL-12 by decidual macrophages. Multiplex fluorescence staining and phenoptics were performed to localize M1-, MOX-, and Mhem-like macrophages in the decidual basalis.
Macrophages displayed diverse phenotypes in the decidua basalis with acute atherosis. M2-like macrophages were the most abundant subset in the decidua; yet, this macrophage subset did not change with the presence of acute atherosis. Decidual M1-like macrophages were increased in acute atherosis, and such macrophages displayed a pro-inflammatory phenotype, as indicated by the expression of iNOS and IL-12. Decidual M1-like pro-inflammatory macrophages were localized near both transformed and non-transformed vessels in the decidua basalis with acute atherosis. MOX and Mhem macrophages were also identified near transformed vessels in the decidua basalis with acute atherosis. Finally, monocyte-like cells were present on the vessel wall of non-transformed decidual vessels, indicating a possible intravascular source for macrophages in acute atherosis.
Decidual macrophages display different phenotypes, namely M1-like, M2-like, MOX, and Mhem subsets. Yet, pro-inflammatory macrophages are enriched in the decidua basalis with acute atherosis. These findings provide a molecular foundation for future mechanistic inquiries about the role of pro-inflammatory macrophages in the pathogenesis of acute atherosis.
急性动脉粥样硬化是一种与妊娠并发症相关的胎盘动脉病变,如子痫前期和早产,后者是全球围产期发病率和死亡率的主要原因。然而,急性动脉粥样硬化的免疫生物学尚不清楚。
从分娩时伴有(n=11)和不伴有(n=31)急性动脉粥样硬化蜕膜基底病变的妇女中收集胎盘基底板样本。使用多色流式细胞术定量分析蜕膜巨噬细胞中 M1 和 M2 样巨噬细胞亚群以及诱导型一氧化氮合酶(iNOS)和白细胞介素-12(IL-12)的表达。进行多重荧光染色和表型分析,以定位蜕膜基底中的 M1、MOX 和 Mhem 样巨噬细胞。
急性动脉粥样硬化的蜕膜基底中巨噬细胞呈现出不同的表型。M2 样巨噬细胞是蜕膜中最丰富的亚群;然而,这种巨噬细胞亚群的数量并没有随着急性动脉粥样硬化的出现而改变。急性动脉粥样硬化时,蜕膜 M1 样巨噬细胞增加,这些巨噬细胞表现出促炎表型,表现为 iNOS 和 IL-12 的表达。蜕膜 M1 样促炎巨噬细胞定位于蜕膜基底中急性动脉粥样硬化的转化和非转化血管附近。MOX 和 Mhem 巨噬细胞也在蜕膜基底的急性动脉粥样硬化转化血管附近被鉴定出来。最后,单核细胞样细胞存在于非转化的蜕膜血管壁上,表明急性动脉粥样硬化中巨噬细胞可能来自血管内。
蜕膜巨噬细胞呈现不同的表型,即 M1 样、M2 样、MOX 和 Mhem 亚群。然而,促炎巨噬细胞在急性动脉粥样硬化的蜕膜基底中富集。这些发现为未来关于促炎巨噬细胞在急性动脉粥样硬化发病机制中的作用的机制研究提供了分子基础。