Abstract
Endometriosis is a continuous and progressive disease with a poorly understood aetiology, pathophysiology and natural history. This study evaluated the histological differences between eutopic and ectopic endometria (abdominal wall endometriosis) and the expression of mast cell proteases (tryptase and chymase), annexin A1 (ANXA1) and formyl peptide receptor 1 (FPR1). Ectopic endometrium from 18 women with abdominal wall endometriosis and eutopic endometrium from 10 women without endometriosis were obtained. The endometrial samples were analysed by histopathology, immunohistochemistry and ultrastructural immunogold labeling to determine mast cell heterogeneity (tryptase and chymase positive cells) and the expression levels of ANXA1 and FPR1. Histopathological analysis of the endometriotic lesions showed a glandular pattern of mixed differentiation and an undifferentiated morphology with a significant influx of inflammatory cells and a change in mast cell heterogeneity, as evidenced by a significant increase in the number of chymase-positive cells and endogenous chymase expression. The undifferentiated glandular pattern of endometriotic lesions was positively associated with a marked increase and co-localization of ANXA1 and FPR1 in the epithelial cells. In conclusion, the co-upregulated expression of mast cell chymase and ANXA1–FPR1 system in ectopic endometrium suggests their involvement in the development of endometriotic lesions.
Similar content being viewed by others
References
Abrao MS, Neme RM, Carvalho FM, Aldrighi JM, Pinotti JA (2003) Histological classification of endometriosis as a predictor of response to treatment. Int J Gynaecol Obstet 82(1):31–40
Accetta I, Accetta P, Accetta AF, Maia FJ, Oliveira AP (2011) Abdominal wall endometrioma. Rev Col Bras Cir 38(1):41–44
Anaf V, Chapron C, El Nakadi I, De Moor V, Simonart T, Noël JC (2006) Pain, mast cells, and nerves in peritoneal, ovarian, and deep infiltrating endometriosis. Fertil Steril 86(5):1336–1343. doi:10.1016/j.fertnstert.2006.03.057
Bai XF, Ni XG, Zhao P, Liu SM, Wang HX, Guo B, Zhou LP, Liu F, Zhang JS, Wang K, Xie YQ, Shao YF, Zhao XH (2004) Overexpression of annexin 1 in pancreatic cancer and its clinical significance. World J Gastroenterol 10(10):1466–1470
Burney RO (2013) The genetics and biochemistry of endometriosis. Curr Opin Obstet Gynecol 25(4):280–286. doi:10.1097/GCO.0b013e3283630d56
D’Acquisto F, Perretti M, Flower RJ (2008) Annexin-A1: a pivotal regulator of the innate and adaptive immune systems. Br J Pharmacol 155(2):152–169. doi:10.1038/bjp.2008.252
Ding Y, Zhu J (2013) A retrospective review of abdominal wall endometriosis in Shanghai. China. Int J Gynaecol Obstet 121(1):41–44. doi:10.1016/j.ijgo.2012.11.011
Dufton N, Perretti M (2010) Therapeutic anti-inflammatory potential of formyl-peptide receptor agonists. Pharmacol Ther 127(2):175–188. doi:10.1016/j.pharmthera.2010.04.010
Dufton N, Hannon R, Brancaleone V, Dalli J, Patel HB, Gray M, D’Acquisto F, Buckingham JC, Perretti M, Flower RJ (2010) Anti-inflammatory role of the murine formyl-peptide receptor 2: ligand-specific effects on leukocyte responses and experimental inflammation. J Immunol 184(5):2611–2619. doi:10.4049/jimmunol.0903526
Fujiwara H, Konno R, Netsu S, Sugamata M, Shibahara H, Ohwada M, Suzuki M (2004) Localization of mast cells in endometrial cysts. Am J Reprod Immunol 51(5):341–344. doi:10.1111/j.1600-0897.2004.00166.x
Gavins FN, Hickey MJ (2012) Annexin A1 and the regulation of innate and adaptive immunity. Front Immunol 3:354. doi:10.3389/fimmu.2012.00354
Gil C, La M, Perretti M, Oliani S (2006) Interaction of human neutrophils with endothelial cells regulates the expression of endogenous proteins annexin 1, galectin-1 and galectin-3. Cell Biol Int 30(4):338–344. doi:10.1016/j.cellbi.2005.12.010
Giudice LC, Kao LC (2004) Endometriosis. Lancet 364(9447):1789–1799. doi:10.1016/S0140-6736(04)17403-5
Ihara T, Uchiide I, Sugamata M (2004) Light and electron microscopic evaluation of antileukotriene therapy for experimental rat endometriosis. Fertil Steril 81(Suppl 1):819–823. doi:10.1016/j.fertnstert.2003.08.029
Jeziorska M, Salamonsen LA, Woolley DE (1995) Mast cell and eosinophil distribution and activation in human endometrium throughout the menstrual cycle. Biol Reprod 53(2):312–320
Jiang QY, Wu RJ (2012) Growth mechanisms of endometriotic cells in implanted places: a review. Gynecol Endocrinol 28(7):562–567. doi:10.3109/09513590.2011.650662
Kamergorodsky G, Ribeiro PA, Galvão MA, Abrão MS, Donadio N, Lemos NL, Aoki T (2009) Histologic classification of specimens from women affected by superficial endometriosis, deeply infiltrating endometriosis, and ovarian endometriomas. Fertil Steril 92(6):2074–2077. doi:10.1016/j.fertnstert.2009.05.086
Kempuraj D, Papadopoulou N, Stanford EJ, Christodoulou S, Madhappan B, Sant GR, Solage K, Adams T, Theoharides TC (2004) Increased numbers of activated mast cells in endometriosis lesions positive for corticotropin-releasing hormone and urocortin. Am J Reprod Immunol 52(4):267–275. doi:10.1111/j.1600-0897.2004.00224.x
Khau T, Langenbach SY, Schuliga M, Harris T, Johnstone CN, Anderson RL, Stewart AG (2011) Annexin-1 signals mitogen-stimulated breast tumor cell proliferation by activation of the formyl peptide receptors (FPRs) 1 and 2. FASEB J 25(2):483–496. doi:10.1096/fj.09-154096
Konno R, Yamada-Okabe H, Fujiwara H, Uchiide I, Shibahara H, Ohwada M, Ihara T, Sugamata M, Suzuki M (2003) Role of immunoreactions and mast cells in pathogenesis of human endometriosis–morphologic study and gene expression analysis. Hum Cell 16(3):141–149
Li CY, Lang JH, Liu HY, Zhou HM (2008) Expression of Annexin-1 in patients with endometriosis. Chin Med J (Engl) 121(10):927–931
Ma F, Kambe N, Wang D, Shinoda G, Fujino H, Umeda K, Fujisawa A, Ma L, Suemori H, Nakatsuji N, Miyachi Y, Torii R, Tsuji K, Heike T, Nakahata T (2008) Direct development of functionally mature tryptase/chymase double-positive connective tissue-type mast cells from primate embryonic stem cells. Stem Cells 26(3):706–714. doi:10.1634/stemcells.2007-0348
Macdonald LJ, Boddy SC, Denison FC, Sales KJ, Jabbour HN (2011) A role for lipoxin A4 as an anti-inflammatory mediator in the human endometrium. Reproduction 142(2):345–352. doi:10.1530/REP-11-0021
Mayran N, Traverso V, Maroux S, Massey-Harroche D (1996) Cellular and subcellular localizations of annexins I, IV, and VI in lung epithelia. Am J Physiol 270(5 Pt 1):L863–L871
Menzies FM, Shepherd MC, Nibbs RJ, Nelson SM (2011) The role of mast cells and their mediators in reproduction, pregnancy and labour. Hum Reprod Update 17(3):383–396. doi:10.1093/humupd/dmq053
Mulla A, Christian HC, Solito E, Mendoza N, Morris JF, Buckingham JC (2004) Expression, subcellular localization and phosphorylation status of annexins 1 and 5 in human pituitary adenomas and a growth hormone-secreting carcinoma. Clin Endocrinol (Oxf) 60(1):107–119
Oliani SM, Christian HC, Manston J, Flower RJ, Perretti M (2000) An immunocytochemical and in situ hybridization analysis of annexin 1 expression in rat mast cells: modulation by inflammation and dexamethasone. Lab Invest 80(9):1429–1438
Oliani SM, Paul-Clark MJ, Christian HC, Flower RJ, Perretti M (2001) Neutrophil interaction with inflamed postcapillary venule endothelium alters annexin 1 expression. Am J Pathol 158(2):603–615
Ostrowski LE, Blackburn K, Radde KM, Moyer MB, Schlatzer DM, Moseley A, Boucher RC (2002) A proteomic analysis of human cilia: identification of novel components. Mol Cell Proteomics 1(6):451–465
Ozel L, Sagiroglu J, Unal A, Unal E, Gunes P, Baskent E, Aka N, Titiz MI, Tufekci EC (2012) Abdominal wall endometriosis in the cesarean section surgical scar: a potential diagnostic pitfall. J Obstet Gynaecol Res 38(3):526–530. doi:10.1111/j.1447-0756.2011.01739.x
Pejler G, Rönnberg E, Waern I, Wernersson S (2010) Mast cell proteases: multifaceted regulators of inflammatory disease. Blood 115(24):4981–4990. doi:10.1182/blood-2010-01-257287
Podgaec S, Abrao MS, Dias JA, Rizzo LV, de Oliveira RM, Baracat EC (2007) Endometriosis: an inflammatory disease with a Th2 immune response component. Hum Reprod 22(5):1373–1379. doi:10.1093/humrep/del516
Polli-Lopes AC, Estofolete CF, Oliani SM, Zucoloto S, Cunha FQ, Gil CD (2013) Myenteric denervation in gastric carcinogenesis: differential modulation of nitric oxide and annexin-A1. Int J Clin Exp Pathol 6(1):13–23
Rodrigo Tapia JP, García Pedrero JM, Pena Alonso E, Fernández MP, Morgan RO, Suárez Nieto C, Herrero Zapatero A (2004) Expression of annexins Al and A2 in the mucosa of the upper airdigestive tract. Acta Otorrinolaringol Esp 55(7):310–314
Sena AA, Provazzi PJ, Fernandes AM, Cury PM, Rahal P, Oliani SM (2006) Spatial expression of two anti-inflammatory mediators, annexin 1 and galectin-1, in nasal polyposis. Clin Exp Allergy 36(10):1260–1267. doi:10.1111/j.1365-2222.2006.02570.x
Sugamata M, Ihara T, Uchiide I (2005) Increase of activated mast cells in human endometriosis. Am J Reprod Immunol 53(3):120–125. doi:10.1111/j.1600-0897.2005.00254.x
Tsao FH, Chen X, Ts’ao CH (1995) Annexin I in female rabbit reproductive organs: varying levels in relation to maturity and pregnancy. Lipids 30(6):507–511
Vishwanatha JK, Muns G, Beckmann JD, Davis RG, Rubinstein I (1995) Differential expression of annexins I and II in bovine bronchial epithelial cells. Am J Respir Cell Mol Biol 12(3):280–286. doi:10.1165/ajrcmb.12.3.7873194
Acknowledgments
This study was supported by FAPESP (2011/00128-1) and CNPq (302768/2010-6). R Paula Junior was supported by CAPES scholarship. The authors thank the resident students of Department of Gynaecology and Obstetrics, São José do Rio Preto School of Medicine (FAMERP) for their crucial help in eutopic endometrium sample collection.
Conflict of interest
The authors have no competing financial interests to disclose in relation to this manuscript.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Paula, R., Oliani, A.H., Vaz-Oliani, D.C.M. et al. The intricate role of mast cell proteases and the annexin A1-FPR1 system in abdominal wall endometriosis. J Mol Hist 46, 33–43 (2015). https://doi.org/10.1007/s10735-014-9595-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10735-014-9595-y