IMMUNOLOCALIZATION AND REGULATION OF THE CHEMOKINE RANTES IN HUNAN ENDOTHELIAL AND ENDOMETRIOSIS TISSUES AND CELLS

Retrograde menstruation is postulated as the initiating event in the h istogenesis of endometriosis; however, subsequent steps in the pathoge nesis of this common disorder remain poorly characterized. The ip accu mulation of activated leukocytes and the infiltration of endometriosis lesions by macrophages and T cells are cytological markers of the inf lammatory nature of this syndrome. The apparent recruitment of these l eukocytes prompted us to search for chemokine expression by endometrio sis cells. We reported previously that pelvic fluid RANTES (regulated upon activation, normal T cell expressed and secreted) concentrations correlated with the stage of endometriosis. In the current study, RANT ES messenger ribonucleic-acid (mRNA) was identified in normal endometr ium and endometriosis lesions, and techniques were developed to locali ze RANTES protein within these tissues. Using isolated endometrial and endometriosis cell cultures, we demonstrated that RANTES mRNA and pro tein can be induced by the proinflammatory cytokines tumor necrosis fa ctor-alpha and interferon-gamma in endometrial stromal, but not in epi thelial or adenocarcinoma cells. Immunocytochemical studies confirmed the biochemical findings. Metabolic labeling experiments verified that nascent RANTES secreted by cytokine-stimulated endometriosis stromal cells was the mature, 8-kDa protein predicted by the mRNA encoding thi s chemokine. The results indicate that RANTES is a normal constituent of the eutopic endometrium. We propose that secretion of RANTES by ect opic endometriosis implants provides a mechanism for peritoneal leukoc yte recruitment.