Pap E, Pállinger E, Falus A, Kiss A A, Kittel A, Kovács P, Buzás E I
Department of Genetics, Cell and Immunobiology, Semmelweis University, Budapest, Hungary.
Placenta. 2008 Sep;29(9):826-32. doi: 10.1016/j.placenta.2008.06.006. Epub 2008 Aug 5.
Microvesicles (MVs) can derive from several cell types and their membranes contain cell surface elements. Their role is increasingly recognized in cell-to-cell communication, as they act as both paracrine and remote messengers, occurring in circulating form as well as in plasma. Successful pregnancy requires a series of interactions between the maternal immune system and the implanted fetus, such that the semi-allograft will not be rejected. These interactions occur at the materno-placental interface and/or at a systemic level. In the present study we identified for the first time the in vivo plasma pattern of the MVs of third-trimester, healthy pregnant women, their cellular origin, and their target cells using flow cytometry and confocal laser microscopy. We searched for the cellular target molecules of thrombocyte-derived MVs with the help of neutralizing antibodies. We examined the in vitro effects of MVs on STAT3 phosphorylation of primary lymphocytes and Jurkat cells. We found that both placental trophoblast-derived and maternal thrombocyte-derived MVs bind to circulating peripheral T lymphocytes, but not to B lymphocytes or NK cells. We were able to show that the P-selectin (CD62P)-PSGL-1 (CD162) interaction is one mechanism binding platelet-derived MVs to T cells. We were also able to demonstrate that MV-lymphocyte interactions induce STAT3 phosphorylation in T cells. Our findings indicate that both thrombocyte- and trophoblast-derived MVs may play an important role in the immunomodulation of pregnancy. We suggest that the transfer of different signals via MVs represents a novel form of communication between the placenta and the maternal immune system, and that MVs contribute to the establishment of stable immune tolerance to the semi-allograft fetus.
微泡（MVs）可源自多种细胞类型，其膜含有细胞表面成分。它们在细胞间通讯中的作用日益受到认可，因为它们既作为旁分泌信使又作为远程信使发挥作用，以循环形式以及在血浆中存在。成功妊娠需要母体免疫系统与植入的胎儿之间进行一系列相互作用，以使半同种异体移植物不会被排斥。这些相互作用发生在母胎 - 胎盘界面和/或全身水平。在本研究中，我们首次使用流式细胞术和共聚焦激光显微镜确定了妊娠晚期健康孕妇的血浆中微泡的模式、其细胞来源及其靶细胞。我们借助中和抗体寻找血小板衍生微泡的细胞靶分子。我们研究了微泡对原代淋巴细胞和Jurkat细胞STAT3磷酸化的体外影响。我们发现胎盘滋养层衍生的微泡和母体血小板衍生的微泡均与循环外周T淋巴细胞结合，但不与B淋巴细胞或NK细胞结合。我们能够证明P - 选择素（CD62P） - PSGL - 1（CD162）相互作用是血小板衍生微泡与T细胞结合的一种机制。我们还能够证明微泡与淋巴细胞的相互作用诱导T细胞中的STAT3磷酸化。我们的研究结果表明，血小板和滋养层衍生的微泡可能在妊娠免疫调节中起重要作用。我们认为，通过微泡传递不同信号代表了胎盘与母体免疫系统之间一种新的通讯形式，并且微泡有助于建立对半同种异体胎儿的稳定免疫耐受。
