D. Hornung et al., IMMUNOLOCALIZATION AND REGULATION OF THE CHEMOKINE RANTES IN HUNAN ENDOTHELIAL AND ENDOMETRIOSIS TISSUES AND CELLS, The Journal of clinical endocrinology and metabolism, 82(5), 1997, pp. 1621-1628
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.