Medeiros Leonardo T L, Peraçoli José C, Bannwart-Castro Camila F, Romão Mariana, Weel Ingrid C, Golim Marjorie A, de Oliveira Leandro G, Kurokawa Cilmery S, Medeiros Borges Vera T, Peraçoli Maria T S
Department of Gynecology and Obstetrics, Botucatu Medical School, São Paulo State University, Botucatu, Brazil.
Am J Reprod Immunol. 2014 Jul;72(1):5-13. doi: 10.1111/aji.12222. Epub 2014 Apr 1.
This study evaluated whether the monocyte inflammatory state in pre-eclampsia (PE) might be associated with polarization to either M1 classically or M2 alternatively activated monocyte subsets.
Eighty-five women with (PE) and 52 normotensive (NT) pregnant women matched for gestational age were included. Expression of surface receptors characteristic of M1, such as Toll-like receptor (TLR)2, TLR4, and CD64, or M2, such as CD163 and CD206 monocyte subsets were evaluated in peripheral blood monocytes by flow cytometry. Tumour necrosis factor-alpha (TNF-α), interleukin-(IL)-12p40, IL-12p70, and IL-10 were evaluated in the supernatant of monocyte cultures by ELISA.
Expression of TLR4 and CD64 by monocytes from pre-eclamptic women was significantly higher, while the expression of CD163 and CD206 expression was significantly lower compared with NT pregnant women. Endogenous production of TNF-α, IL-12p40, and IL-12p70 by monocytes was increased, while synthesis of IL-10 was lower in women with PE than in NT pregnant women.
Monocytes from women with PE are classically activated, producing higher levels of pro-inflammatory cytokines, and express surface receptors characteristic of the M1 subset. These results provide evidence that the systemic inflammatory environment in PE may differentiate and polarize these cells to the M1 phenotype.
本研究评估了子痫前期(PE)患者的单核细胞炎症状态是否可能与向经典M1或替代活化M2单核细胞亚群的极化有关。
纳入85例患有子痫前期(PE)的女性和52例孕龄匹配的血压正常(NT)孕妇。通过流式细胞术评估外周血单核细胞中M1特征性表面受体(如Toll样受体(TLR)2、TLR4和CD64)或M2特征性表面受体(如CD163和CD206单核细胞亚群)的表达。通过酶联免疫吸附测定(ELISA)评估单核细胞培养上清液中的肿瘤坏死因子-α(TNF-α)、白细胞介素-(IL)-12p40、IL-12p70和IL-10。
与血压正常的孕妇相比,子痫前期女性单核细胞中TLR4和CD64的表达显著更高,而CD163和CD206的表达显著更低。子痫前期女性单核细胞内源性产生的TNF-α、IL-12p40和IL-12p70增加,而IL-10的合成低于血压正常的孕妇。
子痫前期女性的单核细胞被经典活化,产生更高水平的促炎细胞因子,并表达M1亚群的特征性表面受体。这些结果提供了证据,表明子痫前期的全身炎症环境可能使这些细胞分化并极化为M1表型。