Hemoglobin-induced continuous activation of macrophages in endometriotic cysts: a potential mechanism of endometriosis development and carcinogenesis
- 4 January 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Medical Molecular Morphology
- Vol. 54 (2), 122-132
- https://doi.org/10.1007/s00795-020-00272-4
Abstract
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-α, 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.Funding Information
- Japan Society for the Promotion of Science (20K09673, 18K09266, 19K09827, 20H03459, 16K09247)
This publication has 28 references indexed in Scilit:
- Possible involvement of signal transducer and activator of transcription-3 in cell–cell interactions of peritoneal macrophages and endometrial stromal cells in human endometriosisFertility and Sterility, 2013
- The association between endometriosis and ovarian cancer: A review of histological, genetic and molecular alterationsGynecologic Oncology, 2012
- Interleukin-6 and other soluble factors in peritoneal fluid and endometriomas and their relation to pain and aromatase expressionJournal of Reproductive Immunology, 2010
- Macrophages Are Alternatively Activated in Patients with Endometriosis and Required for Growth and Vascularization of Lesions in a Mouse Model of DiseaseThe American Journal of Pathology, 2009
- REVIEW ARTICLE: Immunopathogenesis of Pelvic Endometriosis: Role of Hepatocyte Growth Factor, Macrophages and Ovarian SteroidsAmerican Journal of Reproductive Immunology, 2008
- Lipopolysaccharide-promoted proliferation of endometriotic stromal cells via induction of tumor necrosis factor α and interleukin-8 expressionFertility and Sterility, 2004
- Serum and cyst fluid levels of interleukin (IL) -6, IL-8 and tumour necrosis factor-alpha in women with endometriomas and benign and malignant cystic ovarian tumoursHuman Reproduction, 2003
- The peritoneal environment in endometriosisHuman Reproduction Update, 1996
- Immunological aspects of endometriosisHuman Reproduction Update, 1996
- Cytokines in the peritoneal fluid of patients with endometriosisInternational Journal of Gynecology & Obstetrics, 1993