Endometriosis-Associated Macrophages: Origin, Phenotype, and Function

Abstract

Endometriosis is a complex, heterogeneous, chronic inflammatory condition impacting ∼176 million women worldwide. It is associated with chronic pelvic pain, infertility, and fatigue, and has a substantial impact on health-related quality of life. Endometriosis is defined by the growth of endometrial-like tissue outside the uterus, typically on the lining of the pelvic cavity and ovaries (known as "lesions"). Macrophages are complex cells at the center of this enigmatic condition; they are critical for the growth, development, vascularization, and innervation of lesions as well as generation of pain symptoms. In health, tissue-resident macrophages are seeded during early embryonic life are vital for development and homeostasis of tissues. In the adult, under inflammatory challenge, monocytes are recruited from the blood and differentiate into macrophages in tissues where they fulfill functions, such as fighting infection and repairing wounds. The interplay between tissue-resident and recruited macrophages is now at the forefront of macrophage research due to their differential roles in inflammatory disorders. In some cancers, tumor-associated macrophages (TAMs) are comprised of tissue-resident macrophages and recruited inflammatory monocytes that differentiate into macrophages within the tumor. These macrophages of different origins play differential roles in disease progression. Herein, we review the complexities of macrophage dynamics in health and disease and explore the paradigm that under disease-modified conditions, macrophages that normally maintain homeostasis become modified such that they promote disease. We also interrogate the evidence to support the existence of multiple phenotypic populations and origins of macrophages in endometriosis and how this could be exploited for therapy.

Prospects for the Treatment of Endometriosis: The Effect of Immune Peptides on the Reactivation of Immune Surveillance over Ectopic Endometrial Cells

“…Despite the undoubted importance of determining markers of systemic changes in immunity, it is believed that the main role in the pathogenesis of external forms of GE is still the local interaction of the components of the immune system and pathologically altered cells, therefore, the activity of local factors, in particular macrophages of the peritoneal fluid, is of particular importance. Regression or progression of foci of external GE is caused by the interaction of macrophages with stromal endometrial cells with subsequent synthesis of cytokines (interleukins, growth factors, interferons), which cause death or, conversely, increased proliferation of these cells [9][10][11][12][13]. [8].…”

Changes in Peripheral Blood as Manifestation of Disorders in the Mononuclear Phagocyte and Platelet System in Endometriosis

“…Показано, что макрофаги, относящиеся к противовоспалительной субпопуляции (М2), контролируют процессы ремоделирования и репарации в тканях, а также активируют ангиогенез [5]. Именно этот макрофагальный фенотип преимущественно инфильтрирует эндометриоидные очаги [1]. Возникает вопрос о происхождении макрофагов в эндометриоидном очаге: переместились ли они в ретроградно заброшенный фрагмент эндометрия из перитонеальной жидкости, уже находясь в ней, либо макрофаги изначально присутствовали в ткани эндометрия еще до ее менструального распада.…”

“…Термин эндометриоз подразумевает наличие жизнеспособной ткани эктопического эндометрия в различных анатомических локализациях за пределами полости матки. Данная патология наблюдается у 6-10% женщин репродуктивного возраста, 50% из этих женщин страдают бесплодием, а у 71-97% пациенток есть хроническая тазовая боль [1]. Симптоматика данного заболевания негативно влияет на психическое, физическое и социальное благополучие, ухудшая качество жизни [2].…”

Endometriosis and Medical Therapy: From Progestogens to Progesterone Resistance to GnRH Antagonists: A Review

“…Red lesions were found to be very active, with high proliferative activity and vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP) content, explaining their frequent bleeding and remodeling during the menstrual period [ 46 , 47 , 48 ]. Active endometriotic lesions are highly infiltrated by macrophages that are present in the stroma and play a role in the development of the disease [ 49 , 50 ]. These red lesions are resistant to progestin therapy, which may induce some decidualization, but not atrophy [ 46 , 47 , 48 ].…”