Macrophages

There have been several studies on macrophages involved in endometriosis. Let's look first at what, exactly, do macrophages do:

"Macrophages function as control switches of the immune system, providing a balance between pro- and anti-inflammatory responses. To accomplish this, they develop into different subsets: classically (M1) or alternatively (M2) activated macrophages. Whereas M1 macrophages display a cytotoxic, proinflammatory phenotype, much like the soldiers of The Dark Side of The Force in the Star Wars movies, M2 macrophages, like Jedi fighters, suppress immune and inflammatory responses and participate in wound repair and angiogenesis. Critical to the actions of these divergent or polarized macrophage subpopulations is the regulated release of inflammatory mediators. When properly controlled, M1 macrophages effectively destroy invading pathogens, tumor cells, and foreign materials. However, when M1 activation becomes excessive or uncontrolled, these cells can succumb to The Dark Side, releasing copious amounts of cytotoxic mediators that contribute to disease pathogenesis. The activity of M1 macrophages is countered by The Force of alternatively activated M2 macrophages, which release anti-inflammatory cytokines, growth factors, and mediators involved in extracellular matrix turnover and tissue repair. It is the balance in the production of mediators by these two macrophage subpopulations that ultimately determines the outcome of the tissue response to chemical toxicants." http://www.drthrasher.org/page167.html

 

"Macrophages are recruited at sites of hypoxia and tissue stress, where they clear cell debris and heme-iron and generate pro-life and pro-angiogenesis signals. Macrophages are abundant in endometriotic lesions, where are recruited and undergo alternative activation. In rodents macrophages are required for lesions to establish and to grow; bone marrow-derived Tie-2 expressing macrophages specifically contribute to lesions neovasculature, possibly because they concur to the recruitment of circulating endothelial progenitors, and sustain their survival and the integrity of the vessel wall. Macrophages sense cues (hypoxia, cell death, iron overload) in the lesions and react delivering signals to restore the local homeostasis: their action represents a necessary, non-redundant step in the natural history of the disease. Endometriosis may be due to a misperception of macrophages about ectopic endometrial tissue. They perceive it as a wound, they activate programs leading to ectopic cell survival and tissue vascularization. Clearing this misperception is a critical area for the development of novel medical treatments of endometriosis, an urgent and unmet medical need." http://www.ncbi.nlm.nih.gov/pubmed/23372570

"The expression of CD68, NCL-MACRO, HAM56, TNFα, IL-6, and IL-1β was significantly higher in PF macrophages obtained from women with endometriosis than in controls. The ERα and ERβ had significantly higher expression in macrophages of women with endometriosis than in controls. A positive correlation was observed between the expression of ERα and ERβ both in women with and without endometriosis. The ERα expression was positively correlated with the expression of inflammatory cytokines in women with endometriosis but not in controls; ERβ expression was correlated to the expression of inflammatory cytokines in the both groups. There is a correlation between the expression of ERβ and proinflammatory cytokines both in women with and without endometriosis. The expression of ERα correlates with cytokine production selectively in women with endometriosis but not in controls.” http://www.fertstert.org/article/S0015-0282(07)00095-7/abstract

"On the basis of the common occurrence of high concentration of estrogen and activated macrophages in patients with endometriosis, we postulate that interaction between 17beta-estradiol and macrophage may be an important affair in endometriosis. So our study was focused on the effect of 17beta-estradiol on macrophage. First morphology of macrophages was examined with environmental scanning electron microscopy. Increased size, extension of more microvilli, expression of retraction fibers and elaboration of membrane ruffles were detected in 17beta-estradiol treated macrophages. Then Nitrate and nitrite level in the supernatant was measured by the method of Griess and iNOS expression was analyzed using immunohistochemical staining. It showed that 17beta-estradiol could induce NO release from peritoneal macrophages and expression of iNOS was increased. Also more TNF-alpha in supernatant that was measured by MTT via L929 cell was produced by macrophages under the inducing of 17beta-estradiol. Furthermore, [Ca2+]i, which was viewed by microscope in a laser scanning confocal unit, elevated 39.8% in peritoneal macrophages after 17beta-estradiol 100 nmol/L treated. The results above demonstrated that peritoneal macrophage had been activated in both morphology and cytokine line when interaction with 17beta-estradiol, which indicated that macrophage activated by 17beta-estradiol might play a permission role in development of endometriosis." http://www.ncbi.nlm.nih.gov/pubmed/15088640

"Macrophages particularly play important roles in facilitating development, growth, and repair of nerve fibers...Thus the evidence which suggests that the immune cell population, particularly macrophages, are likely to play crucial roles in growth and survival of nerve fibers in endometriosis is compelling, and indicates that certain inflammatory mechanisms may substantially contribute to the generation of pain in endometriosis." Endometriosis: Science and Practice edited by Linda C. Giudice, MD, Johannes L. H. Evers, MD, David L. Healy, MD http://books.google.com/books?id=kxzaBqmglrMC&pg=PA221...

Could this switching of macrophages also be used to help with the inflammation of endometriosis then?

"Macrophages are critical effector cells in the inflammatory response. Classically activated macrophages initiate the innate immune response and direct the activity of the acquired immune response. Upon resolution of inflammation, macrophages convert to an anti-inflammatory phenotype called alternatively activated. Alternatively activated macrophages promote debris scavenging, tissue remodeling and wound healing. Intriguingly, macrophages can be manipulated to move back and forth between these two phenotypes. During inflammatory disorders, like inflammatory bowel disease, switching macrophages to an alternatively activated phenotype, could dampen down inflammation and reduce disease. We are currently assessing the macrophage phenotype present during inflammatory bowel disease and mechanisms that we could use to switch macrophages to an anti-inflammatory phenotype during disease."  http://www.vangopro.ca/Sly-Lab/overview.html

 

It still appears that complete removal of endometriosis lesions is the best therapy.