Immunoendocrinology, Division of Medical Biology, Department of Pathology and Medical Biology, University Medical Centre Groningen and University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
J Reprod Immunol. 2010 Dec;87(1-2):28-38. doi: 10.1016/j.jri.2010.07.005. Epub 2010 Oct 20.
In this study we tested whether plasma from preeclamptic women contains factors that can activate endothelial cells in the presence of monocytes in vitro. Plasma from preeclamptic women (n=6), healthy pregnant women (n=6) and nonpregnant women (n=6) was incubated with mono-cultures and co-cultures of human umbilical vein endothelial cells (HUVEC) and monomac-6 monocytes. Reactive oxygen species (ROS) production and ICAM-1 expression were measured using flow cytometry. Whether scavenging of ROS by superoxide dismutase and catalase inhibited HUVEC ICAM-1 expression was also investigated. We found that in HUVEC co-cultured with monomac-6 cells but not in HUVEC cultured alone, ICAM-1 was upregulated after incubation with plasma from preeclamptic women but not plasma from non-pregnant women. Also in co-cultures, monomac-6 ICAM-1 was upregulated by plasma from preeclamptic women, while in both mono- and co-cultures monomac-6 ROS production was upregulated by plasma from pregnant and preeclamptic women, compared with plasma from non-pregnant women. Scavenging of ROS by superoxide dismutase and catalase resulted in a further upregulation of HUVEC ICAM-1 after incubation with plasma from preeclamptic women, compared with incubation without superoxide dismutase and catalase. These results show that endothelial cells in vitro are activated by plasma of preeclamptic women only if they are co-cultured with monocytes. This upregulation appeared not to be due to extracellular ROS production by monocytes or HUVEC, pointing to involvement of other mechanisms. Our data suggest that plasma of preeclamptic women activates monocytes, and that these monocytes subsequently activate endothelial cells.
在这项研究中，我们测试了子痫前期妇女的血浆中是否含有在体外存在单核细胞的情况下可以激活内皮细胞的因子。将来自子痫前期妇女（n=6）、健康孕妇（n=6）和非孕妇（n=6）的血浆与单核细胞培养物和人脐静脉内皮细胞（HUVEC）和单核细胞-6 （Monomac-6）的共培养物孵育。使用流式细胞术测量活性氧（ROS）的产生和 ICAM-1 的表达。还研究了超氧化物歧化酶和过氧化氢酶对 ROS 的清除是否抑制 HUVEC ICAM-1 的表达。我们发现，在与 Monomac-6 细胞共培养的 HUVEC 中，但不在单独培养的 HUVEC 中，孵育来自子痫前期妇女的血浆后，ICAM-1 上调，但来自非孕妇的血浆则没有。同样在共培养物中，来自子痫前期妇女的血浆上调了 Monomac-6 的 ICAM-1，而在单核和共培养物中，来自孕妇和子痫前期妇女的血浆与来自非孕妇的血浆相比，上调了 Monomac-6 的 ROS 产生。与不添加超氧化物歧化酶和过氧化氢酶相比，用子痫前期妇女的血浆孵育后，ROS 的清除会导致 HUVEC ICAM-1 的进一步上调。这些结果表明，只有在与单核细胞共培养的情况下，子痫前期妇女的血浆才能体外激活内皮细胞。这种上调似乎不是由于单核细胞或 HUVEC 产生的细胞外 ROS 引起的，这表明涉及其他机制。我们的数据表明，子痫前期妇女的血浆激活单核细胞，而这些单核细胞随后激活内皮细胞。
