Fas-Related Apoptosis of Peritoneal Fluid Macrophages in Endometriosis Patients: Understanding the Disease

Abstract

Recent studies of the peritoneal cavity environment in endometriosis demonstrate quantitative and qualitative changes in the cells responsible for cell-mediated immunity. Such changes may have led to disturbances in the surveillance, recognition, and destruction of misplaced endometrial cells and might have, in fact, brought about the disease. The aim of the study was to assess CD95 (Fas) expression on (activated) peritoneal fluid (PF) macrophages, as well as to ascertain soluble Fas (sFas) concentration in the PF of endometriosis patients, as compared to the nonendometriotic group. The concentration of leukocytes in the PF, the percentage of cells expressing CD45+/CD14+, and the percentage of PF macrophages expressing the HLA-DR antigen were significantly higher in patients with stages I and II endometriosis. The percentage of Fas- (CD95+-) expressing macrophages was significantly higher in all stages of the disease, in comparison with controls. Moreover, the concentration of sFas in the PF of patients with moderate and severe endometriosis was significantly higher, as compared to the reference group. The high number of immune cells in PF in early stage endometriosis and their increased susceptibility to apoptosis confirm the role of the impaired peritoneal environment and immune defects in the development and progression of the disease.

Macrophage‐derived insulin‐like growth factor‐1 is a key neurotrophic and nerve‐sensitizing factor in pain associated with endometriosis

“…The pain is thought to be a manifestation of a 2-way dialogue between the nervous system and endometriosis lesions: the presence of endometrial-like tissue in the pelvic cavity of women with endometriosis causes inflammation (39), and lesions are innervated by sensory nerve fibers that sense this peripheral inflammatory environment and generate a nociceptive response resulting in pain perception. Macrophages are the most abundant immune cell present within the pelvic cavity (40), and in women with endometriosis, an increase in the number of macrophages both in the PF (41, 42) and in lesions (43) is evident; thus, these cells may contribute significantly to the inflammatory milieu present in the disease. In our study, we used an established mouse model of endometriosis to demonstrate that macrophage depletion using liposomal clodronate can attenuate endometriosis-associated spontaneous grooming and mechanical hyperalgesia (both locally and at a referred site).…”

Protective role of propofol in endometriosis and its mechanism

“…Following its initiation, the occurrence of cell apoptosis is achieved by transduction of a variety of cell apoptosis signals and is controlled by apoptosis-associated genes (26). In recent years, the association between EM and apoptosis has received increasing attention from researchers (27). Propofol is an intravenous sedative-hypnotic agent, which is employed in the clinic to induce and sustain anesthesia.…”

Ovarian hormones-autophagy-immunity axis in menstruation and endometriosis

“…Among these, macrophages and uNK cells secrete MMP-7 and MMP-9, resulting in the apoptosis of smooth muscle cells and endothelial cells 99 . The proinflammatory cytokines secreted by these immune cells, such as TNF-α, play a role in menstrual shedding, by upregulating the expression of Fas and facilitating Fas-mediated apoptosis 100 . Mast cells in endometrium express tryptase and chymase, likely contributing to menstruation.…”