Hemoglobin-induced continuous activation of macrophages in endometriotic cysts: a potential mechanism of endometriosis development and carcinogenesis

Kusunoki M, Maki Kusunoki, Fujiwara Y, Yukio Fujiwara, Yoshihiro Komohara, Komohara Y, Imamura Y, Yuko Imamura, Ritsuo Honda, Honda R, Takashi Ohba, Ohba T, Hidetaka Katabuchi
Medical molecular morphology · 2021 · vol. 54(2) , pp. 122–132 · doi:10.1007/s00795-020-00272-4 · PMID:33392726 · W3118497657
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⚙ AI-generated summary by claude@2026-06, 2026-06-07 ⓘ

Macrophages in endometriotic cysts, activated by hemoglobin, release inflammatory cytokines like IL-6 and CCL2, potentially driving disease development and carcinogenesis.

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⚙ AI-generated deep summary by claude@2026-06, 2026-06-07 · read from full text ⓘ

This thesis investigated how hemoglobin within endometriotic cysts may drive continuous macrophage activation, using an experimental/analytical approach described as relating to endometriotic lesion progression and malignant transformation. The central finding is that hemoglobin can induce sustained activation of macrophages in the context of endometriotic cysts, proposed as a mechanism that could contribute both to the development of endometriosis and to carcinogenesis. A key limitation is that the work is framed around a potential mechanistic pathway rather than definitive clinical causality. This paper is centrally about endometriosis — specifically, it focuses on hemoglobin-induced continuous macrophage activation in endometriotic cysts as a possible driver of progression and carcinogenic transformation.

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Abstract

Endometriosis is a chronic inflammatory disease. Endometriotic cysts contain hemoglobin (Hb) and infiltrated macrophages, indicating that the metabolism of Hb by macrophages may play an important role in the inflammation of endometriotic cysts. In this study, we investigated the distribution of immune cells and CD163 (Hb receptor)-positive cells in the endometriotic cyst wall using immunohistochemistry. We also examined the role of macrophage activation by Hb on the pathogenesis of endometriotic cysts by measuring the cytokine concentration in the cystic fluids and macrophage-culture supernatant using ELISA. Macrophages were the most prominent immune cells observed in the endometriotic cysts and were differentially distributed in the different histological areas of the cyst wall. The localization of CD163-positive macrophages was restricted to the hemorrhagic and outer areas in the cyst wall. High concentrations of IL-6 and CCL2 were found in the cystic fluids, and inflammatory cytokines (IL-6, TNF-α, and CCL2) were secreted from macrophages on stimulation by Hb. IL-6 is a promotional factor for endometriotic stromal cells and ovarian clear cell carcinoma, the most common histological subtype of endometriosis-related ovarian cancer, hence, the continuous activation of macrophages by Hb could be a potential mechanism underlying endometriosis development and carcinogenesis.
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WEKO3 アイテム 卵巣子宮内膜症性嚢胞においてヘモグロビンにより持続的に活性化されたマクロファージによる子宮内膜症の進展と癌化への寄与の可能性 http://hdl.handle.net/2298/00043788 http://hdl.handle.net/2298/00043788604515cb-3b5c-4b0a-9b13-ba13f3ba3655 | 名前 / ファイル | ライセンス | アクション | |---|---|---| | 審査要旨 (289.8 kB) | | | | 論文要旨 (592.2 kB) | | | | 全文 (1.3 MB) | | | アイテムタイプ | 学位論文 / Thesis or Dissertation(1) | ||||||||||| |---|---|---|---|---|---|---|---|---|---|---|---|---| | 公開日 | 2021-04-22 | ||||||||||| | タイトル | |||||||||||| | タイトル | Hemoglobin-induced continuous activation of macrophages in endometriotic cysts: a potential mechanism of endometriosis development and carcinogenesis | ||||||||||| | 言語 | en | ||||||||||| | タイトル | |||||||||||| | タイトル | 卵巣子宮内膜症性嚢胞においてヘモグロビンにより持続的に活性化されたマクロファージによる子宮内膜症の進展と癌化への寄与の可能性 | ||||||||||| | 言語 | ja | ||||||||||| | 言語 | |||||||||||| | 言語 | eng | ||||||||||| | 資源タイプ | |||||||||||| | 資源タイプ識別子 | http://purl.org/coar/resource_type/c_db06 | ||||||||||| | 資源タイプ | doctoral thesis | ||||||||||| | アクセス権 | |||||||||||| | アクセス権 | open access | ||||||||||| | アクセス権URI | http://purl.org/coar/access_right/c_abf2 | ||||||||||| | 著者 | 楠木, 槙 × 楠木, 槙 | ||||||||||| | 書誌情報 | 発行年 2021-03-25 | ||||||||||| | DOI | |||||||||||| | 関連識別子 | https://doi.org/10.1007/s00795-020-00272-4 | ||||||||||| | 権利 | |||||||||||| | 権利情報 | (C) 2021, The Japanese Society for Clinical Molecular Morphology | ||||||||||| | 権利 | |||||||||||| | 権利情報 | This is a post-peer-review, pre-copyedit version of an article published in [Medical molecular morphology]. The final authenticated version is available online at: https://doi.org/10.1007/s00795-020-00272-4 | ||||||||||| | 著者版フラグ | |||||||||||| | 出版タイプ | VoR | ||||||||||| | 出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | ||||||||||| | 日本十進分類法 | |||||||||||| | 主題 | 377.5 | ||||||||||| | 出版者 | |||||||||||| | 出版者 | 熊本大学 | ||||||||||| | 言語 | ja | ||||||||||| | 学位名 | |||||||||||| | 学位名 | 博士（医学）(ja) | ||||||||||| | 学位授与機関 | |||||||||||| | 学位授与機関名 | 熊本大学 | ||||||||||| | 学位授与年月日 | |||||||||||| | 学位授与年月日 | 2021-03-25 | ||||||||||| | 学位授与番号 | |||||||||||| | 学位授与番号 | 甲第2322号 | ||||||||||| | コメント | |||||||||||| | 値 | 医学教育部 医学専攻 | ||||||||||| | コメント | |||||||||||| | 値 | 本論文を構成する発表論文 Medical molecular morphology, 54(2), 122-132, 2021.【DOI:10.1007/s00795-020-00272-4】 | ||||||||||| | 学位番号 | |||||||||||| | 値 | 甲博医第2322号 |

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Condition tags

endometriosis

MeSH descriptors

Antigens, CD Antigens, Differentiation, Myelomonocytic Carcinogenesis Endometriosis Hemoglobins Interleukin-6 Macrophages Receptors, Cell Surface Adenocarcinoma, Clear Cell Adult CD163 Antigen Cytokines Cytokines Endometriosis Endometriosis Female Hemoglobins Humans Immunohistochemistry Interleukin-6

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