Section of Gynecology and Obstetrics, Academic Department of Biomedicine and Prevention, and Clinical Department of Surgery, Tor Vergata University Hospital, Viale Oxford 81, 00133, Rome, Italy.
Department of Clinical and Experimental Medicine, Linköping University, SE-581 83, Linköping, Sweden.
Sci Rep. 2018 Mar 8;8(1):4166. doi: 10.1038/s41598-018-22418-2.
Low molecular weight heparin (LMWH) is widely used in recurrent miscarriage treatment. The anti-coagulant effects are established, while immunological effects are not fully known. Our aim was to assess LMWH effects on activation and polarization of central regulatory immune cells from healthy women, and on placenta tissues from women undergoing elective abortions. Isolated blood monocytes and T helper (Th) cells under different activation and polarizing conditions were cultured with or without LMWH. Flow cytometry showed that LMWH exposure induced increased expression of HLA-DR and CD206 in macrophages. This phenotype was associated with increased secretion of Th17-associated CCL20, and decreased secretion of CCL2 (M2-associated) and CCL22 (Th2), as measured by multiplex bead array. In accordance, LMWH exposure to Th cells reduced the proportion of CD25highFoxp3+ regulatory T-cells, intensified IFN-γ secretion and showed a tendency to increase the lymphoblast proportions. Collectively, a mainly pro-inflammatory effect was noted on two essential tolerance-promoting cells. Although the biological significancies of these in vitro findings are uncertain and need to be confirmed in vivo, they suggest the possibility that immunological effects of LMWH may be beneficial mainly at an earlier gestational age to provide an appropriate implantation process in women with recurrent miscarriage.
低分子量肝素（LMWH）广泛用于复发性流产的治疗。其抗凝作用已得到证实，但其免疫作用尚不完全清楚。我们的目的是评估 LMWH 对健康女性中央调节性免疫细胞的激活和极化的影响，以及对行选择性流产的妇女胎盘组织的影响。在不同的激活和极化条件下，用或不用 LMWH 培养分离的血液单核细胞和辅助性 T 细胞（Th）。流式细胞术显示，LMWH 暴露诱导巨噬细胞中 HLA-DR 和 CD206 的表达增加。这种表型与 Th17 相关的 CCL20 分泌增加，以及与 M2 相关的 CCL2（CCL2）和与 Th2 相关的 CCL22 分泌减少有关，这是通过多重珠阵列测量的。相应地，LMWH 暴露于 Th 细胞减少了 CD25highFoxp3+调节性 T 细胞的比例，增强了 IFN-γ 的分泌，并表现出增加淋巴母细胞比例的趋势。总的来说，两种重要的耐受促进细胞都表现出主要的促炎作用。尽管这些体外发现的生物学意义尚不确定，需要在体内得到证实，但它们表明 LMWH 的免疫作用可能主要在妊娠早期有益，为复发性流产妇女提供适当的着床过程。
