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

Abstract

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-beta1 (TGF-beta1), 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 FASTQuant 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-beta1, 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-beta1, and VEGF-C within the placental bed.

Immune cells in the placental bed

“…It is possible therefore that uNK cell function may differ between 8 weeks and 12 weeks gestation, although these would both fall within the 'first trimester' group. We have demonstrated gestational age differences in the uNK cell secretion of cytokines and growth factors from 8-10 to 12-14 weeks gestation (Lash et al, 2006b;Naruse et al, 2007a); future studies should focus on subtle gestational age differences which may have a profound effect on function.…”

Efeito do exercício no sistema imune: resposta, adaptação e sinalização celular

“…Although the NK CD56bright cells are mainly found in secondary lymphoid organs 52,58 , these cells are also found in inflammatory sites 58,68 , which may be explained by their great capacity for cytokine production and expression of adhesion molecules targeting them to the injured tissue 58 . In addition to cytokine production, CD56bright cells release many angiogenic growth factors in the uterine circulation 69 , suggesting that, summed to other factors, they can contribute to the angiogenesis, which is a physiological adaptation to regular exercise 59 . Despite these facts, the role of the NK cells associated to exercise should be further investigated.…”

Liaison between natural killer cells and dendritic cells in human gestation

“…Of these hypotheses, the most widely accepted is that dNK cells are derived from CD56 bright CD16 2 pNK cells that are recruited from the blood stream into decidual tissue. Similar to pNK CD56 bright CD16 2 cells, dNK cells do not express CD16, they express the CD94/NKG2A inhibitory receptor, show reduced cytotoxic activity and efficiently produce cytokines, angiogenic growth factors 62,63 and chemokines such as interferon (IFN)-c and tumor-necrosis factor (TNF)-a. 32 However, there are also important differences between CD56 bright pNK cells and their decidual counterparts.…”