Jokhi P P, Chumbley G, King A, Gardner L, Loke Y W
Department of Pathology, University of Cambridge, United Kingdom.
Lab Invest. 1993 Mar;68(3):308-20.
The hematopoietic growth factor colony-stimulating factor-1 (CSF-1) and its receptor (encoded by the proto-oncogene c-fms) are implicated in the regulation of human placental development.
In this study, we have performed a detailed immunohistochemical localization of the CSF-1 receptor (CSF-1R) on cells of the uteroplacental interface in human first trimester pregnancy, supplemented by Northern blot, in situ hybridization, and flow cytometric analysis. CSF-1R expression by JEG-3 and JAR choriocarcinoma cells was also investigated.
c-fms mRNA was detected in primary cultures of first trimester trophoblast and was localized to the extravillous cytotrophoblast columns streaming off the anchoring villi. CSF-1R was expressed by fetal Hofbauer cells in the mesenchyme of the chorionic villi, and this expression increased considerably from first trimester to term. No expression was seen on first trimester and term villous cytotrophoblast. CSF-1R expression on villous syncytiotrophoblast was absent at 6 weeks, strongest at 8-10 weeks, and faded by 12 weeks. First trimester extravillous cytotrophoblast columns were strongly and consistently positive for CSF-1R expression, as was the superficial shell of extravillous trophoblast over the maternal decidua. However, with deeper invasion and terminal differentiation into placental bed giant cells, this expression became weak or absent. Endovascular trophoblast was also only weakly positive for CSF-1R. At the implantation site itself, large numbers of decidual macrophages and CD3-, CD56bright large granular lymphocytes were seen. The macrophages expressed CSF-1R strongly, but large granular lymphocytes, decidual stromal cells, glandular epithelium, and endothelial cells were found to be negative for CSF-1R expression. No CSF-1R expression was detected in JAR choriocarcinoma cells, but CSF-1R was present in first trimester cultured trophoblast and JEG-3 choriocarcinoma cells, although this was shown to be intracellular.
These results suggest that CSF-1 may regulate invasion and differentiation of human placental trophoblast, depending upon the spatial and temporal distribution of its receptor. CSF-1 may also influence placental development and function by acting via decidual and fetal macrophages, which are the other cell populations expressing the receptor.
造血生长因子集落刺激因子-1（CSF-1）及其受体（由原癌基因c-fms编码）与人类胎盘发育的调节有关。
在本研究中，我们对妊娠早期人子宫胎盘界面细胞上的CSF-1受体（CSF-1R）进行了详细的免疫组织化学定位，并辅以Northern印迹、原位杂交和流式细胞术分析。还研究了JEG-3和JAR绒毛膜癌细胞中CSF-1R的表达。
在妊娠早期滋养层细胞的原代培养物中检测到c-fms mRNA，其定位于从固定绒毛流出的绒毛外细胞滋养层柱。CSF-1R在绒毛膜绒毛间充质中的胎儿霍夫鲍尔细胞中表达，并且这种表达从妊娠早期到足月显著增加。在妊娠早期和足月的绒毛细胞滋养层上未观察到表达。绒毛合体滋养层上的CSF-1R表达在6周时不存在，在8-10周时最强，在12周时减弱。妊娠早期绒毛外细胞滋养层柱CSF-1R表达强烈且持续呈阳性，母体蜕膜上的绒毛外滋养层表面壳也是如此。然而，随着更深的浸润和终末分化为胎盘床巨细胞，这种表达变弱或消失。血管内滋养层CSF-1R也仅呈弱阳性。在着床部位本身，可见大量蜕膜巨噬细胞和CD3-、CD56bright大颗粒淋巴细胞。巨噬细胞强烈表达CSF-1R，但大颗粒淋巴细胞、蜕膜基质细胞、腺上皮和内皮细胞CSF-1R表达呈阴性。在JAR绒毛膜癌细胞中未检测到CSF-1R表达，但在妊娠早期培养的滋养层细胞和JEG-3绒毛膜癌细胞中存在CSF-1R，尽管显示其位于细胞内。
这些结果表明，CSF-1可能根据其受体的时空分布调节人胎盘滋养层细胞的侵袭和分化。CSF-1也可能通过蜕膜和胎儿巨噬细胞（表达该受体的其他细胞群体）发挥作用，从而影响胎盘的发育和功能。
