Expression of angiogenic growth factors by uterine natural killer cells during early pregnancy

Expression of angiogenic growth factors by uterine natural killer cells during early pregnancy
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DOI:
10.1189/jlb.0406250
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发表时间:
2006-09-01
影响因子:
5.5
通讯作者:
Bulmer, Judith N.
Bulmer, Judith N.
中科院分区:
医学3区
文献类型:
--
作者:
Lash, Gendie E.;Schiessl, Barbara;Bulmer, Judith N.

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子宫螺旋动脉的重塑对妊娠的成功延续至关重要。子宫自然杀伤细胞(uNK)是妊娠早期蜕膜中主要的白细胞群,这些细胞在妊娠期螺旋动脉重构中起作用。培养48 h后,检测分离的uNK和总(未分离的)蜕细胞(妊娠8-10周或12-14周,每个胎龄n=5)的血管生成生长因子。采用酶联免疫吸附法检测血管生成素(Ang)1、胎盘生长因子、转化生长因子- β 1 (tgf - β 1)和血管内皮生长因子(VEGF)-C。血管生成素、Ang2、成纤维细胞生长因子碱性、细胞间粘附分子(ICAM)-1、角化细胞生长因子(KGF)、血小板衍生生长因子- bb和VEGF-A采用FAST-Quant血管生成生长因子多重蛋白测定法进行测定。总胎分分泌的Ang2、ICAM-1和KGF水平随着胎龄的增加而降低。Ang2和VEGF-C的uNK水平也随着胎龄的增加而下降。妊娠8-10周时,各组uNK细胞分泌的Ang1、Ang2、tgf - β 1、VEGF-C水平及总蜕膜分数均无差异。在12-14周时,uNK细胞分泌的VEGF-C水平明显低于总蜕膜分数。妊娠早期蜕膜是血管生成生长因子的主要来源,其水平随着胎龄的增加而降低,表明它们可能在螺旋动脉重塑中起作用。在胎盘床中,uNK细胞似乎是Ang1、Ang2、tgf - β 1和VEGF-C的重要来源。
Remodeling of uterine spiral arteries is critical for the continuation of a successful pregnancy. Uterine natural killer (uNK) cells are the predominant leukocyte population in the early pregnant decidua, and a role for these cells in spiral artery remodeling in pregnancy has been suggested. Angiogenic growth factors were measured in isolated uNK and total (unseparated) decidual cells (8-10 or 12-14 weeks gestation, n=5 each gestational age) after culture for 48 h. Angiopoietin (Ang)1, placental growth factor, transforming growth factor-beta 1 (TGF-beta 1), and vascular endothelial growth factor (VEGF)-C were measured by enzyme-linked immunosorbent assay. Angiogenin, Ang2, fibroblast growth factor basic, intercellular adhesion molecule (ICAM)-1, keratinocyte growth factor (KGF), platelet-derived growth factor-BB, and VEGF-A were measured using a FAST-Quant angiogenic growth factor multiplex protein assay. Levels of Ang2, ICAM-1, and KGF, secreted by the total decidual fraction, decreased with increasing gestational age. uNK levels of Ang2 and VEGF-C also decreased with increasing gestational age. At 8-10 weeks gestation, there was no difference in the level of Ang1, Ang2, TGF-beta 1, and VEGF-C secreted by uNK cells and the total decidual fraction. At 12-14 weeks, uNK cells secreted significantly lower levels of VEGF-C than the total decidual fraction. Early pregnancy decidua is a major source of angiogenic growth factors whose levels decrease with increasing gestational age, suggesting that they may play a role in spiral artery remodeling. uNK cells appear to be a prominent source of Ang1, Ang2, TGF-beta 1, and VEGF-C within the placental bed.