RANTES production by cultured primate endometrial epithelial cells

PROBLEM: RANTES (regulated upon activation, normal T cell expressed and secreted), is a chemokine with monocyte, macrophage, T lymphocyte, and eosinophil attractant and activating activities. This mediator has been detected in the peritoneal fluid of patients with endometriosis and in cultures of stromal cells from human endometrial and endometriotic tissue. To determine if endometrial epithelial cells were also a potential source of this mediator, primate endometrial epithelial cells were cultured in vitro and the constitutive and stimulated production of RANTES in these cultures was measured. METHOD OF STUDY: Uterine tissue was obtained from Macaca nemestrina monkeys and the endometrial epithelial cells were isolated and placed in culture for 24-72 hr. RANTES was measured in cell extracts and culture fluids by enzyme-linked immunosorbent assay (ELISA). RESULTS: Constitute release of RANTES was low, ranging from 28-52 ng/mL but addition of interferon gamma (INF-gamma) or the combination of IFN-gamma and tumor necrosis factor alpha (TNF-alpha) produced a marked increase in RANTES production. The greatest release, which was nearly 500-fold greater than the basal level, was observed at 72 hr with the combined addition of TNF-alpha and INF-gamma. Nearly 90% of the stimulated RANTES was released into culture fluids, while cell associated RANTES was minimal constituting only 11.2% of the total. CONCLUSION: These findings indicate that endometrial epithelial cells can produce and release RANTES. This chemokine may be an important attractant and activator of macrophages, T lymphocytes and/or eosinophils in the uterus during the reproductive cycle or implantation.