Elevated heme impairs macrophage phagocytosis in endometriosis

Abstract

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 μmol/L, 95% confidence interval (CI): 12.54–16.71), compared with the EMS-free group (9.517 μmol/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 (pMφs) was observed in the EMS group. Consistently, a high-concentration (30 μmol/L) heme treatment impaired EMS-pMφs phagocytosis more than a low-concentration (10 μmol/L) heme treatment. A similar phenomenon was observed in the EMS-free control pMφs (Ctrl-pMφs) 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 pMφs in EMS.

Myoglobin-derived iron causes wound enlargement and impaired regeneration in pressure injuries of muscle

“…Therefore, our measurements will test whether the tissue margins can be saved from dying by Mb knockout and/or iron chelation therapy. Third, prior studies found that high levels of heme/hemin caused impairment of phagocyte functions of chemotaxis and phagocytosis (11,(39)(40)(41)(42)(43). Given that pressure ulcers often have slough or eschar, we hypothesize that phagocytosis will also be impaired in mPI, and that sterile mPI will have slough, despite the absence of bacterial biofilm.…”

SCM-198 Alleviates Endometriosis by Suppressing Estrogen-ERα mediated Differentiation and Function of CD4+CD25+ Regulatory T Cells

“…Assorted immune cells, including NK cells, macrophages and T cells are reported to be dysregulated in patients with EMS. Impaired cytotoxicity of NK cells and reduced phagocytic capacity of macrophages permitted the ectopic endometrium to escape immune surveillance and clearance [10][11][12]27].…”

“…Actually, immune disorder cannot shirk the responsibility in the progress of EMS [8,9]. Weakened phagocytosis ability of macrophages and reduced cytotoxicity of natural killer (NK) cells were found in peritoneal fluid of EMS, which were tightly linked with ectopic lesion formation [10][11][12]. Regulatory T cells (Tregs) have been extensively studied in the region of oncology for their important and irreplaceable role on immune tolerance [13,14].…”

Menstruation Dysregulation and Endometriosis Development

“…Altogether, an inefficient clearance of shed menstrual fragments could prolong the survival of cells increasing the chance for implantation. Furthermore, the presence of uncleared debris and altered macrophage phenotype may further contribute to an inflammatory peritoneal environment promoting the establishment and persistence of endometriosis lesions (19)(20)(21).…”