The role of neutrophils in preeclampsia

Czech version

Authors: E. Miková; J. Hrdý
Authors‘ workplace: Ústav imunologie a mikrobiologie, 1. lékařská fakulta UK a VFN, Praha, přednostka prof. RNDr. L. Kolářová, CSc.
Published in: Ceska Gynekol 2020; 85(3): 206-213
Category:

Overview

Objective: Review of current knowledge about particular neutrophil subsets and their role in preeclampsia.

Design: Review.

Setting: Institute of Immunology and Microbiology, First Faculty of Medicine Charles University and General University Hospital in Prague.

Introduction: Preeclampsia represents one of the major complications of pregnancy with high mortality nowadays. Preeclampsia is a multifactorial disease and to this date, there has not been clear disease trigger identified. Throughout preeclampsia development, an increase in pathophysiological inflammatory response is being present. The induction of inflammation leads to higher number of migrating neutrophils. Current studies demonstrate that neutrophils are a rather heterogeneous population. Deregulation of the ratio between immunoregulatory subpopulations, including polymorphonuclear myeloid–derived suppressor cells, and proinflammatory neutrophil subpopulations could contribute to the induction of inflammatory environment at the feto–maternal interface and subsequently could promote development of pregnancy complications, such as preeclampsia.

Methods and results: In this review, topic of preeclampsia is briefly introduced and a list of distinct neutrophil subsets published in literature is presented.

Conclusion: Unravelling the role of abnormal neutrophil subpopulations migrating to the inflammatory environment of preeclamptic placentas and their role in preeclampsia development could help to identify possible therapeutic targets.

Keywords:

preeclampsia – Neutrophils – polymorphonuclear myeloid–derived suppressor cells – myeloperoxidase – NETosis – inflammation

Sources

1. Ahmadi, M., Mohammadi, M., Ali–Hassanzadeh, M., et al. MDSCs in pregnancy: Critical players for a balanced immune system at the feto–maternal interface. Cell Immunol, 2019, 346, p. 103990.

2. Amsalem, H., Kwan, M., Hazan, A., et al. Identification of a novel neutrophil population: Proangiogenic granulocytes in second–trimester human decidua. J Immunol, 2014, 193(6), p. 3070–3079.

3. Aouache, R., Biquard, L., Vaiman, D., Miralles, F. Oxidative stress in preeclampsia and placental diseases. Int J Mol Sci, 2018, 19(5), p. 1496.

4. Apel, F., Zychlinsky, A., Kenny, EF. The role of neutrophil extracellular traps in rheumatic diseases. Net Rev Rheumatol, 2018, 14(8), p. 467–475.

5. Azizieh, FY., Raghupathy, RG. Tumor necrosis factor-α and pregnancy complications: A prospective study. Med Princ Pract, 2015, 24(2), p. 165–170.

6. Brill, A., Fuchs, TA., Savchenko, AS., et al. Neutrophil extracellular traps promote deep vein thrombosis in mice. 2012, 10(1), p. 136–144.

7. Brinkmann, V., Reichard, U., Goosmann, C., et al. Neutrophil extracellular traps kill bacteria. Science, 2004, 303(5663), p. 1532–1535.

8. Canzoneri, BJ., Lewis, DF., Groome, L., Wang, Y. Increased neutrophil numbers account for leukocytosis in women with preeclampsia. Am J Perinatol, 2009, 26(10), p. 729–32.

9. Cotechini, T., Komisarenko, M., Sperou, A., et al. Inflammation in rat pregnancy inhibits spiral artery remodeling leading to fetal growth restriction and features of preeclampsia. J Exp Med, 2014, 211(1), p. 165–179.

10. Dai, J., El Gazzar, M., Li, GY., et al. Myeloid–derived suppressor cells: Paradoxical roles in infection and immunity. J Innate Immun, 2015, 7(2), p. 116–126.

11. Faas, MM., de Vos, P. Uterine NK cells and macrophages in pregnancy. Placenta, 2017, 56, p. 44–52.

12. Gandley, RE., Rohland, J., Zhou, Y., et al. Increased myeloperoxidase in the placenta and circulation of women with preeclampsia. Hypertension, 2008, 52(2), p. 387–393.

13. Gelber, SE., Brent, E., Redecha, P., et al. Prevention of defective placentation and pregnancy loss by blocking innate immune pathways in a syngeneic model of placental insufficiency. J Immunol, 2015, 195(3), p. 1129–1138.

14. Girardi, G. Complement activation, a threat to pregnancy. Semin Immunopathol, 2018, 40(1), p. 103–111.

15. Gupta, AK., Hasler, P., Holzgreve, W., et al. Induction of neutrophil extracellular DNA lattices by placental microparticles and IL–8 and their presence in preeclampsia. Hum Immunol, 2005, 66(11), p. 1146–1154.

16. Gupta, AK., Joshi, MB., Philippova, M., et al. Activated endothelial cells induce neutrophil extracellular traps and are susceptible to NETosis-mediated cell death. 2010, 584(14), p. 3193–3197.

17. Hahn, S., Giaglis, S., Hoesli, I., Hasler, P. Neutrophil NETs in reproduction: From infertility to preeclampsia and the possibility of fetal loss. Front Immunol, 2012, 3, p. 362.

18. Holthe, MR., Staff, AC., Berge, LN., et al. Calprotectin plasma level is elevated in preeclampsia. Acta Obstet Gynecol Scand, 2005, 84(2), p. 151–154.

19. Kang, X., Zhang, X., Liu, Z., et al. Granulocytic myeloid–derived suppressor cells maintain feto–maternal tolerance by inducing Foxp3 expression in CD4+CD25– T cells by activation of the TGF-β/β–catenin pathway. Mol Hum Reprod, 2016, 22(7), p. 499–511.

20. Kim, SM., Park, JS., Norwitz, ER., et al. Circulating levels of neutrophil gelatinase-associated lipocalin (NGAL) correlate with the presence and severity of preeclampsia. Reprod Sci, 2013, 20(9), p. 1083–1089.

21. Köstlin, N., Kugel, H., Spring, B., et al. Granulocytic myeloid derived suppressor cells expand in human pregnancy and modulate T-cell response. Eur J Immunol, 2014, 44(9), p. 2582–2591.

22. Kropf, P., Baud, D., Marshall, SE., et al. Arginase activity mediates reversible T cell hyporesponsiveness in human pregnancy. Eur J Immunol, 2007, 37(4), p. 935–945.

23. Kucukgoz Gulec, U., Ozgunen, FT., Buyukkurt, S., et al. Comparison of clinical and laboratory findings in early– and late– onset preeclampsia. I Matern Fetal Neonatal Med, 2013, 26(12), p. 1228–1233.

24. Lampé, R., Szucs, S., Adány, R., Póka, R. Granulocyte superoxide anion production and regulation by plasma factors in normal and preeclamptic pregnancy. J Reprod Immunol, 2011, 89(2), p. 199–206.

25. Lampé, R., Kövér, Á, Scűcs, S., et al. Phagocytic index of neutrophil granulocytes and monocytes in healthy and preeclamptic pregnancy. J Reprod Immunol, 2015, 107, p. 26–30.

26. Lampé, R., Kövér, Á, Scűcs, S., et al. The effect of healthy pregnant plasma and preeclamptic plasma on the phagocytosis index of neutrophil granulocytes and monocytes of nonpregnant women. Hypertens Pregnancy, 2017, 36(1), p. 59–63.

27. Lee, KH., Kronbichler, A., Park, DD., et al. Neutrophil extracellular traps (NETs) in autoimmune diseases: A comprehensive review. Autoimmun Rev, 2017, 16(11), p. 1160–1173.

28. Lisonkova, S., Joseph, KS. Incidence of preeclampsia: Risk factors and outcomes associated with early–versus late–onset disease. Am J Obstet Gynecol, 2013, 209(6), p. 544.e1–544.e12.

29. Lynch, AM., Gibbs, RS., Murphy, JR., et al. Early elevations of the complement activation fragment C3a and adverse pregnancy outcomes. Obstet Gynecol, 2011, 117(1), p. 75–83.

30. Nadkarni, S., Smith, J., Sferruzzi–Perri, AN., et al. Neutrophils induce proangiogenic T cells with a regulatory phenotype in pregnancy. Proc Natl Acad Sci USA, 2016, 113(52), p. E8415–E8424.

31. Pelletier, M., Maggi, L., Micheletti, A., et al. Evidence for a cross–talk between human neutrophils and Th17 cells. Blood, 2010, 115(2), p. 335–343

32. Rafaeli–Yehudai, T., Imterat, M., Douvdevani, A., et al. Maternal total cell–free DNA in preeclampsia and fetal growth restriction: Evidence of differences in maternal response to abnormal implantation. PLoS One, 2018, 13(7), p. e0200360.

33. Ramma, W., Buhimischi, IA., Zhao, G., et al. The elevation in circulating anti–angiogenic factors is independent of markers of neutrophil activation in preeclampsia. Angiogenesis, 2012, 15(3), p. 333–340.

34. Regal, JF., Gilbert, JS., Burwick, RM. The complement system and adverse pregnancy outcomes. Mol Immunol, 2015, 67(1), p. 56–70.

35. Rodriguez–Lopez, M., Wagner, P., Perez–Vicente, R., et al. Revisiting the discriminatory accuracy of traditional risk factors in preeclampsia screening. PLoS One, 2017, 12(5), p. e0178528.

36. Roubalová, L., Vojtěch, J., Feyereisl, J., et al. Screening preeklampsie v I. trimestru těhotenství. Čes Gynek, 2019, 84(5), s. 361–370.

37. Ryu, BJ., Han, JW., Kim, RH., et al. Activation of NOD–1/ JNK/IL–8 signal axis in decidual stromal cells facilitates trophoblast invasion. Am J Reprod Immunol, 2017, 78(2).

38. Salazar Garcia, MD., Mobley, Y., Henson, J., et al. Early pregnancy immune biomarkers in peripheral blood may predict preeclampsia. J Reprod Immunol, 2018, 125, p. 25–31.

39. Ssemaganda, A., Kindinger, L., Bergin, P., et al. Characterization of neutrophil subsets in healthy human pregnancies. PLoS One, 2014, 9(2), p. e85696.

40. Sun, L., Mao, D., Cai, Y., et al. Association between higher expression of interleukin–8 (IL–8) and haplotype –353A/– 251A/+678T of IL–8 gene with preeclampsia: A case–control study. Medicine (Baltimore), 2016, 95(52), p. e5537.

41. Sur Chowdhury, C., Hahn, S., Hasler, P., et al. Elevated levels of total cell-free DNA in maternal serum samples arise from the generation of neutrophil extracellular traps. Fetal Diagn Ther, 2016, 40(4), p. 263–267.

42. Thalin, C., Hisada, Y., Lundström, S., et al. Neutrophil extracellular traps: Villains and targets in arterial, venous, and cancer–associated thrombosis. Arterioscler Thromb Vasc Biol, 2019, 39(9), p. 1724–1738.

43. Tsukimori, K., Fukushima, K., Tsushima, A., Nakano, H. Generation of reactive oxygen species by neutrophils and endothelial cell injury in normal and preeclamptic pregnancies. Hypertension, 2005, 46(4), p. 696–700.

44. Tsukimori, K., Tsushima A., Fukushima, K., et al. Neutrophil– derived reactive oxygen species can modulate neutrophil adhesion to endothelial cells in preeclampsia. Am J Hypertens, 2008, 21(5), p. 587–591.

45. Vlk, R. Matěcha, J. Drochýtek, V. Prevence preeklampsie – přehledový článek. Čes Gynek, 2015, 80(3), s. 229–235.

46. Wang, Y., Gu, Y., Philibert, L., Lucas MJ. Neutrophil activation induced by placental factors in normal and pre–eclamptic pregnancies in vitro. Placenta, 2001, 22(6), p. 560–565.

47. Wang, Y., Liu, Y., Shu, C., et al. Inhibition of pregnancy– associated granulocytic myeloid–derived suppressor cell expansion and arginase–1 production in preeclampsia. J Reprod Immunol, 2018, 127, p. 48–54.

48. Wójtowicz, A., Zembala–Szczerba, M., Babczyk, D., et al. Early- and late-onset preeclampsia: A comprehensive cohort study of laboratory and clinical findings according to the new ISHHP criteria. Int J Hypertens, 2019, 2019, p. 4108271

49. Zhao, H., Kalish, F., Schulz, S., et al. Unique roles of infiltrating myeloid cells in the murine uterus during early to midpregnancy. J Immunol, 2015, 194(8), p. 3713–3722.

50. Zhong, LM., Liu, ZG., Zhou, X., et al. Expansion of PMN–myeloid derived suppressor cells and their clinical relevance in patients with oral squamous cell carcinoma. Oral Oncol, 2019, 95, p. 157–163.