Chemokine bioactivity of RANTES in endometriotic and normal endometrial stromal cells and peritoneal fluid

Endometriotic lesions secrete chemokines that recruit immune cells into the peritoneal cavity, The accumulation of these immune cells, especially acti vated macrophages and T lymphocytes, is thought to mediate inflammatory sym ptoms associated with endometriosis. Previous studies have demonstrated tha t RANTES (regulated on activation, normal T cell expressed and secreted) is synthesized by endometriotic stromal cells and circulates in peritoneal fl uid, commensurate with the stage of endometriosis. In the current studies, we used the human monocytic cell line, U937, to assay chemotactic activity in cell culture conditioned media and peritoneal fluid from patients with e ndometriosis and normal controls. We demonstrated expression of the human R ANTES receptors CCR-1 and CCR-5 in U937 cells and peritoneal macrophages. O ver a range of 0-1000 pg/ml recombinant human RANTES had a direct, linear e ffect on monocyte migration. Conditioned media and peritoneal fluid induced dose-dependent effects on monocyte migration that were correlated with con centrations of immunoreactive RANTES las measured by enzyme-linked immunoso rbent assay) and the severity of endometriosis. Heat denaturation of the RA NTES protein or addition of anti-human RANTES antibodies neutralized the ch emoattractant effects of conditioned media and peritoneal fluid. RANTES sti mulation of monocyte recruitment may be an important pathogenetic target fo r the treatment of infertility and pain associated with endometriosis.