Regulated on activation normal T expressed and secreted chemokine is induced by tumor necrosis factor-alpha in granulosa cells from human preovulatory follicle

We examined the production of regulated on activation normal T expressed an d secreted (RANTES) chemokine, which may contribute to the recruitment and local accumulation of leukocytes in human preovulatory follicles. Cells wer e obtained from follicular aspirates collected from in vitro fertilization patients, then cultured. RANTES production in culture was measured by immun oenzymatic assay, RANTES-producing cells were measured by flow cytometry, a nd messenger ribonucleic acid as measured by RT-PCR and in situ hybridizati on. RANTES was detected in follicular fluids and culture supernatants; RANT ES protein and messenger ribonucleic acid were expressed in granulosa cells . RANTES production was stimulated by tumor necrosis factor-alpha (TNF alph a) and was inhibited in cultures containing a neutralizing anti-TNF alpha a ntibody, p55 TNF receptors were detected by RT-PCR and visualized on granul osa cells by flow cytometry. RANTES production was increased by phorbol 12- myristate 13-acetate, but not by 8-bromo-cAMP. RANTES was produced by granu losa cells from human preovulatory follicles. This production was activated by TNF alpha, probably through TNF receptor p55. This suggests that RANTES may play an active role in ovarian processes involving the local accumulat ion of immune cells.