Hemoglobin-induced continuous activation of macrophages in endometriotic cysts: a potential mechanism of endometriosis development and carcinogenesis

Endometriosis is a chronic inflammatory disease. Endometriotic cysts contain hemoglobin (Hb) and infiltrated macrophages, indicating that the metabolism of Hb by macrophages may play an important role in the inflammation of endometriotic cysts. In this study, we investigated the distribution of immune cells and CD163 (Hb receptor)-positive cells in the endometriotic cyst wall using immunohistochemistry. We also examined the role of macrophage activation by Hb on the pathogenesis of endometriotic cysts by measuring the cytokine concentration in the cystic fluids and macrophage-culture supernatant using ELISA. Macrophages were the most prominent immune cells observed in the endometriotic cysts and were differentially distributed in the different histological areas of the cyst wall. The localization of CD163-positive macrophages was restricted to the hemorrhagic and outer areas in the cyst wall. High concentrations of IL-6 and CCL2 were found in the cystic fluids, and inflammatory cytokines (IL-6, TNF-alpha, and CCL2) were secreted from macrophages on stimulation by Hb. IL-6 is a promotional factor for endometriotic stromal cells and ovarian clear cell carcinoma, the most common histological subtype of endometriosis-related ovarian cancer, hence, the continuous activation of macrophages by Hb could be a potential mechanism underlying endometriosis development and carcinogenesis.

Automated summary

Endometriosis is a chronic inflammatory disease characterized by the presence of endometriotic cysts containing hemoglobin and infiltrated macrophages. The study found that macrophages were the predominant immune cells in the cysts, with CD163-positive macrophages mainly localized in the hemorrhagic and outer areas of the cyst wall. High levels of IL-6 and CCL2 were detected in the cystic fluids, and inflammatory cytokines were secreted from macrophages when stimulated by Hb, suggesting a potential mechanism for the development and carcinogenesis of endometriosis.