Pathophysiology and Immune Dysfunction in Endometriosis

Figure 1

An overview of immune cells and mediators involved in the promotion of neovascularization and endometriotic lesion growth on the peritoneal membrane. In women with endometriosis, high levels of angiogenic factors and inflammatory cytokines are found in the peritoneal fluid (PF). Development of blood vessels of the lesions depends on two processes: vasculogenesis and angiogenesis. Vasculogenesis is mediated by recruitment and incorporation of the bone marrow- (BM-) derived endothelial progenitor cells (EPCs) to proliferating blood vessels in the endometriotic lesions. Recruitment of BM-derived EPCs is facilitated by stromal cell-derived factor- (SDF-) 1. Vascular endothelial growth factor (VEGF) and other angiogenic factors including interleukin- (IL-) 6, IL-8, and tumor necrosis factor- (TNF-) α mediate the process of angiogenesis by activating angiogenic switch of endothelial cells. Local production of estradiol by the lesion maintains the expression of VEGF and promotes the production of VEGF and monocyte chemoattractant protein- (MCP-) 1 by the macrophages. In women with endometriosis, natural killer (NK) cell cytotoxicity is diminished, which may be due to increased expression of IL-10 in the PF. Immature dendritic cells (DCs) express VEGFR-2 on the surface and thus are theorized to play a role in angiogenesis by interacting with VEGF. The integrated role of immune cells and mediators is a complicated process and requires further studies to piece together the details available to fully appreciate their role in the pathogenesis of endometriosis.