Elevated heme impairs macrophage phagocytosis in endometriosis
Elevated heme impairs macrophage phagocytosis in endometriosis
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子宫内膜异位症中血红素升高会损害巨噬细胞的吞噬作用
DOI：
10.1530/rep-19-0028
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发表时间：
2019-09-01
期刊：
影响因子：
3.8
通讯作者：
Zhu, Xiao-Yong
中科院分区：
文献类型：
--
作者：
Liu, Yu-Yin;Liu, Yu-Kai;Zhu, Xiao-Yong
子宫内膜异位症（EMS）是一种慢性炎症性疾病，其特征是存在子宫外的子宫内膜组织。以往的研究表明，子宫内膜异位症的发病机制可能与子宫内膜异位症的血液回流和腹腔巨噬细胞清除功能障碍有关。然而，巨噬细胞在EMS中表现出减弱的吞噬能力的机制仍然不确定。在此，我们发现，血红素，溶解红细胞的副产物，异常积累在腹膜液（PF）的EMS患者（14.22 μ mol/L，95%置信区间（CI）：12.54-16.71），与EMS组（9.517 μ mol/L，95% CI：8.891-10.1053）相比。这种异常积累与PF的颜色、月经周期的阶段或疾病的严重程度无关。EMS组腹腔巨噬细胞吞噬能力（pM φ s）降低。一致地，高浓度（30 μ mol/L）血红素处理损害EMS-pM φ s吞噬作用比低浓度（10 μ mol/L）血红素处理。在无EMS对照pM phi s（Ctrl-pM phi s）和CD 14（+）外周单核细胞（CD 14（+）Mos）中观察到类似的现象。这些结果表明，高浓度的血红素对巨噬细胞吞噬作用表现出负面影响，这补充了EMS中pM phi s的清除功能受损的机制。
Endometriosis (EMS) is a chronic inflammatory disease characterized by the presence of extrauterine endometrial tissues. It has been previously reported that the refluxed blood containing viable endometrial tissues and the defective elimination of peritoneal macrophages in the pelvic cavity may involve in EMS pathogenesis. However, the mechanism by which macrophages exhibit attenuated phagocytic capability in EMS remains undetermined. Herein, we found that heme, the byproduct of lysed erythrocytes, accumulated abnormally in the peritoneal fluid (PF) of patients with EMS (14.22 mu mol/L, 95% confidence interval (CI): 12.54-16.71), compared with the EMS-free group (9.517 mu mol/L, 95% CI: 8.891-10.1053). This abnormal accumulation was not associated with the color of PF, phase of the menstrual cycle or severity of the disease. The reduced phagocytic ability of peritoneal macrophages (pM phi s) was observed in the EMS group. Consistently, a high-concentration (30 mu mol/L) heme treatment impaired EMS-pM phi s phagocytosis more than a low-concentration (10 mu mol/L) heme treatment. A similar phenomenon was observed in the EMS-free control pM phi s (Ctrl-pM phi s) and the CD14(+) peripheral monocytes (CD14(+) Mos). These results indicated that a high heme concentration exhibits a negative effect on macrophage phagocytosis, which supplements the mechanism of impaired scavenger function of pM phi s in EMS.