Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University, 333 Cedar St., P. O. Box 208063, New Haven, CT 06520, USA.
Placenta. 2012 Mar;33(3):188-94. doi: 10.1016/j.placenta.2011.12.007. Epub 2011 Dec 31.
As human blastocyst-derived extravillous trophoblasts (EVTs) invade the early decidua, they are positioned to interact with immune cells and resident decidual cells, and remodel spiral arteries into high capacity vessels that increase blood flow to the developing fetal-placental unit. Shallow EVT invasion elicits incomplete vascular transformation and reduces uteroplacental blood flow that presages adverse pregnancy outcomes. Excess macrophages in the decidua induce EVT apoptosis via tumor necrosis factor-alpha (TNF-α) secretion. Our previous observation that pro-inflammatory cytokines enhance neutrophil and macrophage activator granulocyte-macrophage colony-stimulating factor (GM-CSF) expression in first trimester decidual cells is now extended to include: (1) the specific macrophage activator M-CSF; (2) macrophage activation and subsequent enhancement of EVT apoptosis by both GM-CSF and M-CSF.
Quantitative reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay assessed M-CSF expression in first trimester decidual cells incubated with interleukin-1 beta (IL-1β) or TNF-α. Peripheral monocyte-derived macrophages pre-incubated with conditioned media from decidual cell cultures were co-cultured with a first trimester EVT cell line, HTR-8/SVneo cells. Macrophage activation was examined and EVT apoptosis evaluated by DNA fragmentation, caspase activation and cell membrane asymmetry.
IL-1β or TNF-α significantly enhanced M-CSF expression in first trimester decidual cells. The conditioned media from these cultures activates macrophages, which promote caspase 3/7-dependent EVT apoptosis with antibodies against GM-CSF or M-CSF blocking this effect.
Pro-inflammatory cytokines increases synthesis of M-CSF in first trimester decidual cells. Both GM-CSF and M-CSF activate macrophages, which initiate caspase-dependent EVT apoptosis.
人类囊胚衍生的绒毛外滋养细胞（EVT）侵入早期蜕膜时，它们处于与免疫细胞和常驻蜕膜细胞相互作用的位置，并重塑螺旋动脉成为高容量血管，增加流向发育中的胎儿胎盘单位的血流量。EVT 浸润不足会引起血管转化不完全，并减少胎盘血流量，预示着不良的妊娠结局。蜕膜中过多的巨噬细胞通过肿瘤坏死因子-α（TNF-α）分泌诱导 EVT 凋亡。我们之前的观察结果表明，促炎细胞因子增强了早孕蜕膜细胞中中性粒细胞和巨噬细胞激活因子粒细胞-巨噬细胞集落刺激因子（GM-CSF）的表达，现在扩展到包括：（1）特定的巨噬细胞激活剂 M-CSF；（2）GM-CSF 和 M-CSF 对巨噬细胞的激活以及随后对 EVT 凋亡的增强。
定量逆转录聚合酶链反应和酶联免疫吸附试验评估了白细胞介素 1β（IL-1β）或 TNF-α孵育的早孕蜕膜细胞中 M-CSF 的表达。预先用蜕膜细胞培养物的条件培养基孵育的外周单核细胞衍生的巨噬细胞与早孕 EVT 细胞系 HTR-8/SVneo 细胞共培养。通过 DNA 片段化、半胱天冬酶激活和细胞膜不对称性评估巨噬细胞的激活和 EVT 凋亡。
IL-1β 或 TNF-α 显著增强了早孕蜕膜细胞中 M-CSF 的表达。这些培养物的条件培养基激活了巨噬细胞，用 GM-CSF 或 M-CSF 抗体阻断这种作用可促进半胱天冬酶 3/7 依赖性 EVT 凋亡。
促炎细胞因子增加了早孕蜕膜细胞中 M-CSF 的合成。GM-CSF 和 M-CSF 均可激活巨噬细胞，引发依赖半胱天冬酶的 EVT 凋亡。
