EPITHELIAL-CELLS ARE THE MAJOR SOURCE OF BIOLOGICALLY-ACTIVE GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR IN HUMAN ENDOMETRIUM

Granulocyte macrophage colony-stimulating factor (GM-CSF) has emerged as an important growth factor for trophoblast and other placental cell s, leading to improved placental functioning and fetal survival, Recen t observations have indicated that GM-CSF is synthesized by epithelial cells in the murine pregnant and non-pregnant uterus, In this study, the production of GM-CSF by cells derived from human endometrium is as sessed using a sensitive bioassay and specific neutralization of the c ytokine bioactivity with a monoclonal antibody to GM-CSF, Originally, GM-CSF was assayed in the culture supernatants of explant cultures of human endometria, Concentrations of GM-CSF up to 4440 pg/ml were detec ted, Subsequently, enriched epithelial cell cultures were prepared fro m glands isolated from human endometrium, The purity of epithelial cul tures was demonstrated by the expression of cytokeratin, a weak immuno reactivity for vimentin and a lack of immunoreactivity for leukocyte c ommon antigen, CD68, a macrophage-specific protein and endothelial mar ker (factor VIII-related antigens), Detected concentrations of GM-CSF were as high as 18 800 pg/ml, Furthermore, pure epithelial cells of a neoplastic endometrial cell line ECC1 secreted GM-CSF, confirming the ability of endometrial epithelial cells to secrete this cytokine, The immunostaining of dated endometria from proliferative and secretory ph ases showed primarily that epithelial cells, and to a lesser extent st romal cells, exhibited immunoreactivity for GM-CSF, A Western blot ana lysis, performed to validate the immunohistochemical data, confirmed t he presence of an immunoreactive gene product for GM-CSF in human endo metrium throughout the menstrual cycle, These findings indicate that h uman endometrium synthesizes GM-CSF and that epithelial cells are a ma jor contributor to its production.