Hornung D, Dohrn K, Sotlar K, Greb R R, Wallwiener D, Kiesel L, Taylor R N
Department of Obstetrics and Gynecology, University of Tübingen, Germany.
J Clin Endocrinol Metab. 2000 Jul;85(7):2604-8. doi: 10.1210/jcem.85.7.6665.
Our laboratories have focused recently on the production and localization of eotaxin, a C-C-chemokine of 8.4 kDa, whose major biological activity is the chemoattraction of eosinophils. Given evidence of autoimmune activity in the endometriosis syndrome, we hypothesized that eosinophil chemoattractants might be expressed in endometriosis. In histological sections, we observed eotaxin protein localized mainly in epithelial cells, with only very faint immunostaining in the surrounding stromal cells. Prominent eotaxin accumulation was noted in the luminal epithelium of secretory endometrium. Eotaxin distribution in endometriosis was similar to that seen in eutopic endometrium but with higher levels of eotaxin staining in the glandular epithelium. Peritoneal fluid concentrations of eotaxin were significantly higher in women with moderate or severe endometriosis than in women with minimal or mild endometriosis or no disease. The treatment of isolated human endometriosis epithelial cells with estradiol, medroxyprogesterone acetate, tumor necrosis factor-alpha, and interferon-gamma stimulated measurable eotaxin secretion into the conditioned media. The results indicate that eotaxin is produced in epithelial cells of normal endometrium and endometriosis tissues, varies across the menstrual cycle, and is elevated in women with endometriosis. We postulate that eotaxin, interacting with other known cytokines and immune cells, contributes to an inflammatory reproductive tract environment, leading to endometrial or blastocyst dysfunction.
我们的实验室最近专注于嗜酸性粒细胞趋化因子(一种8.4 kDa的C-C趋化因子)的产生和定位,其主要生物学活性是嗜酸性粒细胞的化学吸引作用。鉴于子宫内膜异位症综合征存在自身免疫活性的证据,我们推测嗜酸性粒细胞趋化因子可能在子宫内膜异位症中表达。在组织学切片中,我们观察到嗜酸性粒细胞趋化因子蛋白主要定位于上皮细胞,周围基质细胞仅有非常微弱的免疫染色。在分泌期子宫内膜的腔上皮中发现了明显的嗜酸性粒细胞趋化因子积聚。嗜酸性粒细胞趋化因子在子宫内膜异位症中的分布与在位内膜相似,但腺上皮中的嗜酸性粒细胞趋化因子染色水平更高。中度或重度子宫内膜异位症女性的腹水中嗜酸性粒细胞趋化因子浓度显著高于轻度或极轻度子宫内膜异位症女性或无疾病女性。用雌二醇、醋酸甲羟孕酮、肿瘤坏死因子-α和干扰素-γ处理分离的人子宫内膜异位症上皮细胞,可刺激其向条件培养基中分泌可测量的嗜酸性粒细胞趋化因子。结果表明,嗜酸性粒细胞趋化因子在正常子宫内膜和子宫内膜异位症组织的上皮细胞中产生,在月经周期中有所变化,且在子宫内膜异位症女性中升高。我们推测,嗜酸性粒细胞趋化因子与其他已知细胞因子和免疫细胞相互作用,导致生殖道炎症环境,进而导致子宫内膜或胚泡功能障碍。