Jokhi P P, King A, Loke Y W
Department of Pathology, University of Cambridge, UK.
Hum Reprod. 1994 Sep;9(9):1660-9. doi: 10.1093/oxfordjournals.humrep.a138769.
Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a classical haematopoietic cytokine which has been implicated in placental growth and development. In this study, we investigated the production of GM-CSF in human first trimester pregnancy by the predominant uterine lymphocyte population of decidual CD56+ NK cells (large granular lymphocytes) and the factors that influence this production using enzyme-linked immunosorbent assays (ELISAs) and bioassays, supplemented by immunocytochemistry. We have also investigated and compared production of GM-CSF by human first trimester trophoblast and by JEG-3 and JAR choriocarcinoma cells. Our data show that appreciable amounts of GM-CSF are produced in first trimester maternal decidua and that a significant component of this secretion was from decidual large granular lymphocytes (LGL). Production of GM-CSF by LGL was constitutive and considerably greater than that of freshly isolated peripheral blood leukocytes. GM-CSF secretion by decidual LGL could be enhanced by co-culture on a monolayer of decidual stromal cells, and could also be increased in a dose-dependent manner by stimulation with interleukin-1 (IL-1) or IL-2. IL-4, IL-6, tumour necrosis factor alpha (TNF alpha), transforming growth factor beta (TGF beta), interferon alpha (IFN alpha) and IFN gamma individually had no effect on GM-CSF secretion, although IL-4, TGF beta and IFN alpha all inhibited the action of IL-2. IFN gamma had no effect on the IL-2-induced GM-CSF secretion, but did antagonize the action of IL-1. Normal human first trimester trophoblast was also found to produce GM-CSF, although no production whatsoever was seen by JEG-3 or JAR choriocarcinoma cells. These results suggest that GM-CSF from uterine lymphocytes, and from trophoblast itself, may influence placental growth and development in both a paracrine and an autocrine manner.
粒细胞-巨噬细胞集落刺激因子（GM-CSF）是一种经典的造血细胞因子，与胎盘的生长和发育有关。在本研究中，我们利用酶联免疫吸附测定（ELISA）和生物测定，并辅以免疫细胞化学，研究了人孕早期蜕膜中主要的子宫淋巴细胞群——蜕膜CD56+自然杀伤细胞（大颗粒淋巴细胞）产生GM-CSF的情况以及影响这种产生的因素。我们还研究并比较了人孕早期滋养层细胞以及JEG-3和JAR绒毛膜癌细胞产生GM-CSF的情况。我们的数据表明，孕早期母体蜕膜中产生了相当数量的GM-CSF，且这种分泌的一个重要组成部分来自蜕膜大颗粒淋巴细胞（LGL）。LGL产生GM-CSF是组成性的，且大大高于新鲜分离的外周血白细胞。蜕膜LGL与蜕膜基质细胞单层共培养可增强GM-CSF的分泌，用白细胞介素-1（IL-1）或IL-2刺激也可使其以剂量依赖的方式增加。单独的IL-4、IL-6、肿瘤坏死因子α（TNFα）、转化生长因子β（TGFβ）、干扰素α（IFNα）和IFNγ对GM-CSF分泌均无影响，尽管IL-4、TGFβ和IFNα均抑制IL-2的作用。IFNγ对IL-2诱导的GM-CSF分泌无影响，但可拮抗IL-1的作用。正常的人孕早期滋养层细胞也被发现可产生GM-CSF，尽管JEG-3或JAR绒毛膜癌细胞未观察到任何产生。这些结果表明，来自子宫淋巴细胞和滋养层自身的GM-CSF可能以旁分泌和自分泌方式影响胎盘的生长和发育。
