Macrophages, oxidation, and endometriosis

Retrograde menstruation has been suggested to be the cause for the presence of endometrial cells in the peritoneal cavity. However, little is known about the events that lead to the adhesion and growth of these cells that ultimately result in endometriosis, considering the fact that the disease occurs only in certain women despite the common occurrence of retrograde menstruation in most women. We postulate that, in normal women, the endometrial cells and tissue that arrive in the peritoneal cavity during menstruation are effectively removed by macrophages that are chemoattracted and become resident tissue macrophages in the peritoneal cavity. In contrast, the peritoneal macrophages in women with endometriosis are nonadherent and ineffectively scavenged, resulting in the sustained presence and growth of the endometrial cells. We also postulate that the peritoneal fluid is not a passive reservoir of the factors secreted by cells of the peritoneum, but actively promotes endometriosis. The peritoneal fluid is rich in lipoproteins, particularly low-density lipoprotein, which generates oxidized lipid components in a macrophage-rich inflammatory milieu. The oxidants exacerbate the growth of endometriosis by inducing chemoattractants such as MCP-1 and endometrial cell growth-promoting activity. We provide evidence for the presence of oxidative milieu in the peritoneal cavity of women with endometriosis, the nonscavenging properties of macrophages that are nonadherent, and the synergistic interaction between macrophages, oxidative stress, and the endometrial cells. For example, the peritoneal fluid lipoproteins of subjects with endometriosis have increased the propensity to undergo oxidation as compared with plasma lipoproteins, and the subjects also have increased titer of autoantibodies to oxidatively modified proteins. If the oxidative proinflammatory nature of the peritoneal fluid is an important mediator of endometriosis growth, anti-inflammatory agents and antioxidants might afford protection against endometriosis.