Immunology: 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.

IGF-I Overexpression Causes Fetal Loss during Placentation in Mice

“…A l t e r n a t i v e l y , I G F -I overexpression may affect the decidual stromal cells. Decidual cells, stimulated by IGF-I, could produce some factors including TGF-β and extracellular matrix, which can change the characteristics of uNK cells [7,22,23]. This is the first report to demonstrate that IGF-I overexpression can cause fetal loss during murine placentation.…”

“…These results suggest that IGF-I plays a role in differentiation of the endometrial stroma cells to the decidual cells. Decidual cells are known to produce various factors including IL-15, TGF-β, HGF and extracellular matrix that regulate the maternal placenta development [6,7,8]. On the other hand, uterine NK (uNK) cells, specific lymphocytes found throughout pregnancy, differentiate with the progress of placental development and are known to have significant function in the maintenance of pregnancy through stimulating angiogenesis in the placenta [9,10].…”

Cyclosporin A improves murine pregnancy outcome in abortion-prone matings: involvement of CD80/86 and CD28/CTLA-4

“…After the invasion into the decidua, trophoblasts, carrying paternal antigens, are in close contact with the maternal immune cells. Amazingly, the maternal immunocompetent cells do not attack the embryo, and even cooperate with trophoblasts via the production of some cytokines and growth factors to participate in the establishment of a unique materno-fetal immune milieu that helps the fetus to survive and develop in the uterus till parturition (Saito et al 1993, Jokhi et al 1994a, 1994b, Saito 2000, Veenstra van Nieuwenhoven et al 2003, Higuma-Myojo et al 2005, Staun-Ram & Shalev 2005. Thus, there is a subtle chorus rather than simple rivalry between the distinguished cells.…”

Tumor-related leukocytosis is linked with poor prognosis in patients with lung carcinoma

“…Several hematopoietic cytokines have been identified from tumor cells or established tumor cell lines. [5][6][7][8][9][10] In previous reports, the majority of lung carcinomas were associated with G-CSF production, 11,12 and a few cases were associated with granulocyte-macrophage-colony stimulating factor (GM-CSF) 13 and interleukin-6 (IL-6) production. 14 However, the incidence and clinical characterization of TRL in patients with lung carcinoma have not been clarified.…”