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Functional and phenotypic alterations in peritoneal macrophages from patients with early and advanced endometriosis
A Raiter-Tenenbaum1, R I Barañao, J J Etchepareborda
1Instituto de Biología y Medicina Experimental-CONICET, Buenos Aires, Argentina.
Abstract:
The aim of this study was to elucidate whether peritoneal macrophage (pMO) alterations are a generalized feature in all stages of endometriosis and the effect of hormonal treatment on this leukocyte population. For this purpose we quantified the number of pMO, the expression of HLA-DR antigen (pMO DR+), percentages of pMO that reduced nitro-blue tetrazolium (pMO NBT+), and interleukin-1 (IL-1) and prostaglandin E2 (PGE2) production by pMO from patients with early (stages I/II) and advanced (stages III/IV) endometriosis, we also analyzed some of these properties in pMO from patients which had been treated for 6 months with 800 mg/day of Danazol or gonadotropin releasing hormone agonist (GnRHa). We found that there were a significant increase of the pMO number in both types of patients, though the highest values were obtained in early endometriosis (p < 0.001). Percentages of pMO DR+ were decreased in all patients (p < 0.01) while percentages of pMO NBT+ were significantly increased. Production of IL-1 by early and advanced endometriosis pMO were considerably enhanced. PGE2 release was not altered in early endometriosis pMO but, in advanced endometriosis, pMO PGE2 levels were 100-fold higher than control values. In posttreatment patients, the number of pMO and percentage of pMO NBT+ were similar to early endometriosis patients, though the percentage of pMO DR+ was within the normal range. We conclude that the pMO population, as well as IL-1 and PGE2 production, were altered in all stages of endometriosis, and that these changes could be involved in the pathogenesis of endometriosis and associated infertility. Hormonal treatments do not reverse the pMO changes.
Insights
Endometriosis alters peritoneal macrophages (pMO) in all stages, increasing their numbers and IL-1 production while decreasing HLA-DR expression. Hormonal treatments do not reverse these changes in pMO.
Area of Science:
- Immunology
- Reproductive Medicine
- Cell Biology
Background:
- Endometriosis is a chronic inflammatory condition affecting women of reproductive age.
- Peritoneal macrophages (pMO) play a crucial role in the peritoneal environment and immune responses.
- Alterations in pMO function may contribute to endometriosis pathogenesis and associated infertility.
Purpose of the Study:
- To investigate if peritoneal macrophage (pMO) alterations are a generalized feature across all stages of endometriosis.
- To determine the effect of hormonal treatments (Danazol and GnRHa) on pMO populations in endometriosis patients.
Main Methods:
- Quantification of pMO number, HLA-DR antigen expression (pMO DR+), and nitro-blue tetrazolium reduction (pMO NBT+) in pMO.
- Measurement of interleukin-1 (IL-1) and prostaglandin E2 (PGE2) production by pMO.
- Analysis of pMO properties in early (I/II) and advanced (III/IV) endometriosis patients, and in patients treated with Danazol or GnRHa.
Main Results:
- pMO numbers were significantly increased in all endometriosis stages, particularly early stages.
- pMO DR+ percentages decreased, while pMO NBT+ percentages increased across all stages.
- IL-1 production was enhanced in pMO from both early and advanced endometriosis patients.
- PGE2 levels were significantly elevated in advanced endometriosis pMO, showing a 100-fold increase.
- Hormonal treatments did not reverse the observed pMO alterations.
Conclusions:
- Peritoneal macrophage populations and their production of IL-1 and PGE2 are altered in all stages of endometriosis.
- These pMO alterations may contribute to endometriosis pathogenesis and associated infertility.
- Current hormonal treatments do not restore pMO characteristics to normal levels.