The role of the macrophage polarization type in the pathogenesis of endometrioid disease

Authors

DOI:

https://doi.org/10.14739/2310-1210.2021.5.233689

Keywords:

endometriosis, macrophages, peritoneal fluid

Abstract

Endometriosis today occupies one of the leading places in the structure of general gynecological pathology. Theories of the onset and progression of this disease are controversial. One of the most widespread theories is the assumption that endometriosis is a disease of macrophages. The question of which the macrophage phenotype, M1 or M2, is the leading one, however, remains controversial.

The aim. To determine the type of macrophage polarization (M1/M2) and the quantitative activity of their marker enzymes (iNos/Arg1) in the endometrium and peritoneal fluid in endometrioid disease.

Materials and methods. The total number of reproductive age (30.95±6.49) women enrolled in the study was 80. The main group consisted of 50 women with endometrioid disease. The control group included 30 women without signs of endometrioid disease. Women from the main group (n=24) and the control group (n=27) underwent endometrial sampling using an intrauterine Pipelle catheter in the first phase of the menstrual cycle before a surgery. During laparoscopic or laparotomy approaches, peritoneal fluid was taken (in the main group n=24, in the control group n=28). The type of macrophage polarization (M1 or M2) was determined based on the ratio of marker enzymes (Arg1, iNos) activity in each patient using a spectrophotometric method in the endometrium and peritoneal fluid. The polarization to the M1 phenotype was determined at iNos>Arg1, and at Arg1>iNos– the polarization to the M2 phenotype.

Results. As a result of the study, it was revealed that in women with endometrioid disease, pelvic adhesions were much more common, 84.0% versus 46.7% in women without it, and especially 3 and 4 degree of severity (P<0.05). When assessing the type of macrophages in the peritoneal fluid, a significantly greater number of the main group women had the M2 phenotype of macrophage polarization compared to the control group (58.3% versus 28.6%, P=0.03). It was the macrophage polarization to the M2 phenotype that influenced the severity of endometrioid disease, especially the 4 degree of severity. The mean values of the iNOS activity in the main group women, both in the peritoneal fluid and in the endometrium, significantly differed from those in the control group patients (by 1.73 and 1.77 times, respectively).

Conclusions. Thus, we can conclude that endometriosis is a disease, the development and progression of which is induced by the M2 phenotype of macrophages. Considering the increase in the mean levels of iNOS activity both in the peritoneal fluid and in the endometrium, it can be concluded that iNOS influences the pathogenesis of endometrioid disease.

Author Biographies

Y. А. Orlova, Poltava State Medical University, Ukraine

MD, PhD student of the Department of Obstetrics and Gynecology No. 1

A. М. Gromova, Poltava State Medical University, Ukraine

MD, PhD, DSc, Professor, Head of the Department of Obstetrics and Gynecology No. 1

O. Ye. Akimov, Poltava State Medical University, Ukraine

MD, PhD, Lecturer of the Department of Pathophysiology

O. М. Ketova, Poltava State Medical University, Ukraine

PhD, Assistant of the Department of Obstetrics and Gynecology No. 1

References

Pshenichnyuk, E. Yu., Asaturova, A. V., Adamyan, L. V., & Zaitsev, N. V. (2018). Immunogistokhimicheskie osobennosti eutopicheskogo i ektopicheskogo endometriya u patsientok s retsidiviruyushchim techeniem endometrioidnykh kist yaichnikov [Immunohistochemical features of eutopic and ectopic endometrium in patients with recurrent ovarian endometrioid cysts]. Akusherstvo i ginekologiya, (3), 84-95. https://doi.org/10.18565/aig.2018.3.84-95 [in Russian].

Baranov, V. S. (2013). Endometrioz kak problema sistemnoi genetiki [Endometriosis as systemic genetic problem]. Zhurnal akusherstva i zhenskikh boleznei, 62(1), 71-78. https://doi.org/10.17816/JOWD62171-78 [in Russian].

Wang, Y., Nicholes, K., & Shih, I. M. (2020). The Origin and Pathogenesis of Endometriosis. Annual Review of Pathology: Mechanisms of Disease, 15, 71-95. https://doi.org/10.1146/annurev-pathmechdis-012419-032654

Sokolov, D. I., Kondratjeva, P. G., Jarmolinskaja, M. I., Kramareva, N. L., Seljutin, A. V., Rulev, V. V, Niauri, D. A. & Selkov, S. A. (2014). Soderzhanie khemokinov i tsitokinov v peritoneal'noi zhidkosti bol'nykh naruzhnym genital'nym endometriozom razlichnoi stepeni tyazhesti [Contents of chemokines and cytokines in peritoneal fluid from the patients with endometriosis of various severity]. Meditsinskaya immunologiya, 9(1), 85-90. https://doi.org/10.15789/1563-0625-2007-1-85-90 [in Russian].

Wu, J., Xie, H., Yao, S., & Liang, Y. (2017). Macrophage and nerve interaction in endometriosis. Journal of Neuroinflammation, 14(1), Article 53. https://doi.org/10.1186/s12974-017-0828-3

Monastyrskaya, E. A., Lyamina, S. V., & Malyshev, I. Yu. (2008). M1 i M2 fenotipy aktivirovannykh makrofagov i ikh rol' v immunnom otvete i patologii [Ml and М2 phenotypes of activated macrophages and their role in immune response and pathology]. Patogenez, 6(4), 31-39. [in Russian].

Ponomarenko, I. V., Koneva, O. A., & Altukhova, O. B. (2016). Molekulyarnye osnovy etiopatogeneza i kliniki endometrioza [Molecular basis of pathogenesis and clinical endometriosis]. Nauchnye vedomosti Belgorodskogo gosudarstvennogo universiteta. Seriya: Meditsina. Farmatsiya, (19), 11-16. [in Russian].

Podgaec, S., Dias Junior, J. A., Chapron, C., Oliveira, R. M., Baracat, E. C., & Abrão, M. S. (2010). Th1 and Th2 ummune responses related to pelvic endometriosis. Revista da Associação Médica Brasileira, 56(1), 92-98. https://doi.org/10.1590/s0104-42302010000100022

de Campos, G. Y., Oliveira, R. A., Oliveira-Brito, P., Roque-Barreira, M. C., & da Silva, T. A. (2020). Pro-inflammatory response ensured by LPS and Pam3CSK4 in RAW 264.7 cells did not improve a fungistatic effect on Cryptococcus gattii infection. PeerJ, 8, Article e10295. https://doi.org/10.7717/peerj.10295

Kumar, S., Gupta, E., Gupta, N., Kaushik, S., Srivastava, V. K., Kumar, S., Mehta, S., & Jyoti, A. (2021). Functional role of iNOS-Rac2 interaction in neutrophil extracellular traps (NETs) induced cytotoxicity in sepsis. Clinica Chimica Acta, 513, 43-49. https://doi.org/10.1016/j.cca.2020.12.004

Ministry of Health of Ukraine. (2006, April 06). Pro zatverdzhennia ta vprovadzhennia medyko-tekhnolohichnykh dokumentiv zi standartyzatsii medychnoi dopomohy pry henitalnomu endometriozi [On Approval and implementation of the medical and technological documents on standardizing the management of genital endometriosis (No. 319)]. https://www.dec.gov.ua/mtd/genitalnyj-endometrioz/

Yelins’ka, A. M., Akimov, O. Ye., & Kostenko, V. O. (2019). Role of AP-1 transcriptional factor in development of oxidative and nitrosative stress in periodontal tissues during systemic inflammatory response. The Ukrainian Biochemical Journal, 91(1), 80-85. https://doi.org/10.15407/ubj91.01.080

Akimov, O. Ye., & Kostenko, V. O. (2020). Role of NF-κB transcriptional factor activation during chronic fluoride intoxication in development of oxidative-nitrosative stress in rat's gastric mucosa. Journal of Trace Elements in Medicine and Biology, 61, Article 126535. https://doi.org/10.1016/j.jtemb.2020.126535

Akimov, O. Ye., & Kostenko, V. O. (2016). Functioning of nitric oxide cycle in gastric mucosa of rats under excessive combined intake of sodium nitrate and fluoride. The Ukrainian Biochemical Journal, 88(6), 70-75. https://doi.org/10.15407/ubj88.06.070

Zakharov, I. S., Ushakova, G. A., Demyanova, T. N., Bolotova, S. N., Fetischeva, L. E., Petrich, L. N. & Dodonova, G. H. (2016). Spaechnaya bolezn' organov malogo taza: sovremennye vozmozhnosti profilaktiki [Adhesive disease of the pelvic organs: modern prevention opportunities]. Consilium Medicum, 18(6), 71-73. https://doi.org/10.26442/2075-1753_2016.6.71-73 [in Russian].

Working group of ESGE, ESHRE and WES, Saridogan, E., Becker, C. M., Feki, A., Grimbizis, G. F., Hummelshoj, L., Keckstein, J., Nisolle, M., Tanos, V., Ulrich, U. A., Vermeulen, N., & De Wilde, R. L. (2017). Recommendations for the Surgical Treatment of Endometriosis. Part 1: Ovarian Endometrioma. Human Reproduction Open, 2017(4), Article hox016. https://doi.org/10.1093/hropen/hox016

Miller, J. E., Ahn, S. H., Marks, R. M., Monsanto, S. P., Fazleabas, A. T., Koti, M., & Tayade, C. (2020). IL-17A Modulates Peritoneal Macrophage Recruitment and M2 Polarization in Endometriosis. Frontiers in Immunology, 11, Article 108. https://doi.org/10.3389/fimmu.2020.00108

Burns, K. A., Thomas, S. Y., Hamilton, K. J., Young, S. L., Cook, D. N., & Korach, K. S. (2018). Early Endometriosis in Females Is Directed by Immune-Mediated Estrogen Receptor α and IL-6 Cross-Talk. Endocrinology, 159(1), 103-118. https://doi.org/10.1210/en.2017-00562

Hudson, Q. J., Ashjaei, K., Perricos, A., Kuessel, L., Husslein, H., Wenzl, R., & Yotova, I. (2020). Endometriosis Patients Show an Increased M2 Response in the Peritoneal CD14+low/CD68+low. Macrophage Subpopulation Coupled with an Increase in the T-helper 2 and T-regulatory Cells. Reproductive Sciences, 27(10), 1920-1931. https://doi.org/10.1007/s43032-020-00211-9

Shamarakova, M. V., Adamyan, L. V., Asaturova, A. V., Ezhova, L. S., Zaitsev, N. V., Yurova, M. V., & Martirosyan, Ya. O. (2018). Seromutsinoznye opukholi yaichnikov i endometrioz u zhenshchin reproduktivnogo vozrasta [Seromucinous ovarian tumors and endometriosis in reproductive-aged women]. Akusherstvo i ginekologiya, (7), 84-91. https://doi.org/10.18565/aig.2018.7.84-91 [in Russian].

Kielbik, M., Szulc-Kielbik, I., & Klink, M. (2019). The Potential Role of iNOS in Ovarian Cancer Progression and Chemoresistance. International Journal of Molecular Sciences, 20(7), Article 1751. https://doi.org/10.3390/ijms20071751

Yeo, S. G., Won, Y. S., Lee, H. Y., Kim, Y. I., Lee, J. W., & Park, D. C. (2013). Increased Expression of Pattern Recognition Receptors and Nitric Oxide Synthase in Patients with Endometriosis. International Journal of Medical Sciences, 10(9), 1199-1208. https://doi.org/10.7150/ijms.5169

Yu, J., Chen, L. H., Zhang, B., & Zheng, Q. M. (2019). The modulation of endometriosis by lncRNA MALAT1 via NF-κB/iNOS. European Review for Medical and Pharmacological Sciences, 23(10), 4073-4080. https://doi.org/10.26355/eurrev_201905_17908

Dhall, S., Coksaygan, T., Hoffman, T., Moorman, M., Lerch, A., Kuang, J. Q., Sathyamoorthy, M., & Danilkovitch, A. (2018). Viable cryopreserved umbilical tissue (vCUT) reduces post-operative adhesions in a rabbit abdominal adhesion model. Bioactive Materials, 4(1), 97-106. https://doi.org/10.1016/j.bioactmat.2018.09.002

Published

2021-09-01

How to Cite

1.
Orlova YА, Gromova AМ, Akimov OY, Ketova OМ. The role of the macrophage polarization type in the pathogenesis of endometrioid disease. Zaporozhye Medical Journal [Internet]. 2021Sep.1 [cited 2024Jul.3];23(5):644-50. Available from: http://zmj.zsmu.edu.ua/article/view/233689

Issue

Section

Original research