Elevated heme impairs macrophage phagocytosis in endometriosis

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.