Production of granulocyte-macrophage colony-stimulating factor by human trophoblast cells and by decidual large granular lymphocytes.

Abstract

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.