Spatial and temporal expression of ligands for CXCR3 and CXCR4 in human endometrium.

In this study, we investigated the expression of ligands for CXCR3 (Mig, IP-10, and I-TAC) and CXCR4 (SDF-1) in the human endometrium throughout the menstrual cycle. By immunohistochemistry, immunostaining for Mig and IP-10 was found in the surface epithelia, glandular epithelia, and stroma with some menstrual cycle-dependent fluctuation. By contrast, immunostaining for I-TAC or SDF-1 was not detected. ELISA demonstrated that the concentrations of Mig and IP-10 were higher in the secretory phase than in the proliferative phase, but I-TAC and SDF-1alpha was detected in only a few samples. Endometrial Mig and IP-10 concentrations strongly correlated with the number of endometrial natural killer cells. Progesterone significantly induced Mig secretion and tended to induce IP-10 secretion from the cultured endometrial stromal cells, whereas 17beta-estradiol had no significant effect. Neither I-TAC nor SDF-1alpha was detected in the supernatant of cultured endometrial stromal cells in the presence or absence of 17beta-estradiol or progesterone. The results suggest that Mig and IP-10 may be involved in the recruitment of natural killer cells or other phenomena in the human endometrium.

Expression of macrophage inflammatory protein-3beta in human endometrium throughout the menstrual cycle.

OBJECTIVE: To determine the expression of macrophage inhibitory protein-3beta (MIP-3beta), a potential chemoattractant for endometrial natural killer (NK) cells, in the human endometrium. DESIGN: An experimental study. SETTING: University department of obstetrics and gynecology. PATIENT(S): Thirty-seven fertile women with regular menstrual cycles and nonpathological endometrium, undergoing hysterectomy. INTERVENTION(S): Endometrium was obtained from operative samples. MAIN OUTCOME MEASURE(S): Paraffin-embedded endometrium was immunostained to determine the localization of MIP-3beta. The number of NK cells was counted in 10 nonoverlapping stromal areas. The MIP-3beta concentration in the homogenized endometrium was determined by ELISA. RESULT(S): Immunoreactivity for MIP-3beta was observed in the surface epithelia, glandular epithelia, and stroma with some menstrual cycle-dependent fluctuation. The MIP-3beta concentration was significantly higher in the late secretory phase than in the other phases. It showed a trend toward correlation with the number of endometrial NK cells. CONCLUSION(S): MIP-3beta was expressed in the human endometrium, but our results could not strongly support the hypothesis that MIP-3beta is a potential chemoattractant for endometrial NK cells.

Fluctuation of 6Ckine expression in human endometrium during the menstrual cycle.

OBJECTIVE: To clarify the expression of 6Ckine, a potential chemoattractant for endometrial natural killer (NK) cells, in the human endometrium. DESIGN: Experimental study. SETTING: Department of obstetrics and gynecology at a medical university. PATIENT(S): Fifty-seven fertile women 25 to 52 years of age who had regular menstrual cycles and normal endometrium and were undergoing hysterectomy. INTERVENTION(S): Endometrium was obtained from operative samples. MAIN OUTCOME MEASURE(S): Tissue was immunostained to determine the localization of 6Ckine in the endometrium throughout the menstrual cycle. The number of NK cells was counted in 10 nonoverlapping stromal areas. The concentration of 6Ckine in homogenized endometrium was determined by enzyme-linked immunosorbent assay. RESULT(S): Endometrial surface, glandular epithelial cells, and perivascular stromal cells were immunoreactive for 6Ckine throughout the menstrual cycle with some fluctuation. In addition, some T cells, NK cells, and macrophages in the stroma were immunoreactive for 6Ckine. The 6Ckine concentration was low in the proliferative phase but elevated in the secretory phase. It showed a moderate positive correlation with the number of endometrial NK cells. CONCLUSION(S): 6Ckine may be a potential chemoattractant for endometrial NK cells.

Potential selectin L ligands involved in selective recruitment of peripheral blood CD16(-) natural killer cells into human endometrium.

Unique CD16(-) natural killer (NK) cells appear in the human cycling endometrium and acutely increase in number after ovulation. Selective recruitment from peripheral blood (PB) CD16(-) NK cells is a potential mechanism for the postovulatory increase of these NK cells. The interaction between selectin L, an adhesion molecule playing a critical role in leukocyte extravasation, and its ligands may be involved in this phenomenon. We investigated the menstrual cycle-dependent fluctuation of selectin L expression on PB CD16(-) NK cells and selectin L ligand expression in the human endometrial endothelium. The expression of selectin L on PB CD16(-) NK cells was constantly high throughout the menstrual cycle compared with other PB CD16(+) NK cells and non-NK lymphocytes. Among eight selectin L ligands examined, podocalyxin-like, mucosal addressin cell adhesion molecule-1 (MADCAM1) and chondroitin sulfate proteoglycan 2 (CSPG2) were localized in the endometrial endothelium. Semiquantitative score of immunostaining intensity in the endometrial endothelium for MADCAM1 was highest in the late secretory phase, whereas that for CSPG2 peaked throughout the secretory phase. There was a strong positive correlation between the number of endometrial NK cells and the semiquantitative score for CSPG2. Three active isoforms of CSPG2 mRNA were detected in the human endometrium. These findings support the idea that the interaction between selectin L and selectin L ligands functions in the postovulatory selective recruitment of PB CD16(-) NK cells into the human endometrium.

Interferon regulatory factor-1 expression in human uterine endometrial carcinoma.

OBJECTIVES: The objective was to investigate the expression of interferon regulatory factors 1 (IRF-1) in human uterine endometrial carcinoma. METHODS: Formalin-fixed, paraffin-embedded, archival tissue specimens from 76 human endometrial carcinomas and stained with polyclonal anti-IRF-1 antibody, using immunohistochemistry, localization, and immunostaining, were evaluated quantitatively using the H score together with 30 normal endometrium and 16 postmenopausal endometrium. RESULTS: The expression of IRF-1 was highest in normal endometrium, and decreased with the grade of endometrioid adenocarcinoma from grade 1 to grade 3. Postmenopausal endometrium was virtually unstained. CONCLUSIONS: Expression of IRF-1 is altered in human endometrioid adenocarcinoma compared with normal endometrium and postmenopausal endometrium. The loss of IRF-1 expression does not contradict with the tumor-suppressor function. The intensity of IRF-1 expression in each grade of endometrioid adenocarcinoma could be useful prognostic and therapeutic indicators.