巨噬细胞参与调节胎盘的免疫和形态发生事件。然而,胎盘巨噬细胞(Hofbauer细胞)的这些作用尚不清楚。这项研究的目的是表征妊娠早期和晚期胎盘巨噬细胞中细胞因子产生(细胞内合成和分泌)的连续步骤,并比较胎盘巨噬细胞和绒毛组织的分泌谱。
在妊娠9-12周或38-40周时从正常妊娠获得的胎盘中分离巨噬细胞和绒毛组织。用单克隆抗体染色后,通过流式细胞术确定细胞内细胞因子。通过细胞计数珠阵列和ELISA定量分泌的细胞因子。
在胎盘巨噬细胞中揭示了细胞因子产生的两种模式。第一组中的细胞因子(IL-1,IL-6,IL-8,IL-10,TNFα)显示出低的基础产生,并受到细菌内毒素的刺激。第二组中的细胞因子(IL-11,IL-17A,IL-17F,TGF-β,VEGF)的特征是组成型产生,对刺激没有反应。观察到妊娠年龄依赖性变化:与妊娠早期细胞相比,妊娠晚期巨噬细胞中TNFα和IL-8的基础分泌增加,而IL-11和IL-17的分泌减少。细胞和组织水平上细胞因子产生的比较表明胎盘巨噬细胞在胎盘内和胎盘外细胞因子产生中的作用。
可以安全地假设细胞因子产生的两种模式,在我们的研究中透露,对应于胎盘巨噬细胞的两种调节作用:“免疫”和“形态发生”。巨噬细胞的炎症表型在妊娠早期减弱,并随着妊娠的进展而增加。第一组的细胞因子可能有助于局部和胎盘外水平,而第二组的细胞因子效应更可能局限于胎盘组织。
Macrophages participate in the regulation immune and morphogenetic events in the placenta. However, these roles remain unclear for placental macrophages (Hofbauer cells). The aims of this study were to characterize the consecutive steps of cytokine production (intracellular synthesis and secretion) in placental macrophages in early and late gestation and to compare the secretory profiles of placental macrophages and villous tissue.
Macrophages and villous tissue were isolated from placentas obtained from normal pregnancies at either 9-12 or 38-40 weeks of gestation. Intracellular cytokines were determined by flow cytometry after staining with monoclonal antibodies. Secreted cytokines were quantified by cytometric bead array and ELISA.
Two patterns of cytokine production were revealed in placental macrophages. Cytokines in the first group (IL-1, IL-6, IL-8, IL-10, TNFα) demonstrated low basal production and were stimulated by bacterial endotoxin. Cytokines in the second group (IL-11, IL-17A, IL-17F, TGF-β, VEGF) were characterized by constitutive production and did not respond to stimulation. Gestational age-dependent changes were observed: basal secretion of TNFα and IL-8 increased whereas IL-11 and IL-17 secretion decreased in third-trimester macrophages compared with the first-trimester cells. Comparison of cytokine production at the cellular and tissue levels suggested the contribution of the placental macrophages both in intraplacental and extraplacental cytokine production.
It would be safe to assume that the two patterns of cytokine production, revealed in our study, correspond to two regulatory roles of placental macrophages: \"immune\" and \"morphogenetic\". The inflammatory phenotype of macrophages is attenuated in early gestation and increases with the progression of pregnancy. The cytokines of the first group supposedly contribute to both local and extraplacental levels, whereas the cytokine effects of the second group are more likely confined to the placental tissue.