M1マクロファージとM2マクロファージ

M1・M2という概念の形成

M1マクロファージ、M2マクロファージという言い方をよく聞きますが、これはM1やM2という2種類のマクロファージが存在するという意味ではありません。同じマクロファージの2つの状態をそれぞれM1、M2と呼んでいるのです。M1,M2マクロファージという考え方は2000年頃にHillらによって提唱されたもの(Mills  et al., 2000; J Immunol 164:6166-6173)だそうです。「状態」なので2つの状態を行き来する可能性もあります。

  1. マクロファージ学~その歴史と現在地 佐藤 荘 実験医学2018年9月号 疾患を制御するマクロファージの多様性

M1マクロファージとM2マクロファージの特徴

Macrophages undergo specific differentiation in different tissue environments, and can be divided into two different polarization states: M1 type macrophages (M1) and M2 type macrophages (M2). M1 can respond to dangerous signals transmitted by bacterial products or IFN-γ, which attracting and activating cells of the adaptive immune system; an important feature of M1 is that it can express nitric oxide synthase (iNOS) and reactive oxygen species (ROS) (15–17) and cytokine IL-12 (18). M1 also has the function of engulfing and killing target cells. M2 expresses a large number of scavenger receptors, which is related to the high-intensity expression of IL-10, IL-1β, VEGF and matrix metalloprotein (MMP) (19, 20). M2 has the function of removing debris, promoting angiogenesis, tissue reconstruction and injury repairments, as well as promoting tumorigenesis and development (4). It is worth noting that the polarization of macrophages into M2 appears to be oversimplified. Some people have classified M2 macrophages into M2a (induced by IL-4 or IL-13), M2b (induced by immune complexes combined with IL-1β or LPS) and M2c (induced by IL-10, TGFβ, or glucocorticoid), and M2d (conventional M2 macrophages that exert immunosuppression) (21, 22). https://www.frontiersin.org/articles/10.3389/fimmu.2020.583084/full

M1マクロファージとM2マクロファージとのバランス

Patients with M2/M1 < 3 had significantly improved progression-free survival and overall survival compared with patients with M2/M1 > 3. M1 and M2 macrophages elicited opposite effects on colon cancer progression via the FBW7-MCL-1 axis. https://www.nature.com/articles/s12276-020-0436-7

マクロファージの多様性

役割によってM1型・M2型に大別されると考えられているが、佐藤荘准教授は、単純なM1・M2という振り分け方ではなく、生体内には更に多様なマクロファージが存在すると仮定。実験により、様々な疾患に特異的に働くマクロファージが複数存在していることを立証した。(https://resou.osaka-u.ac.jp/ja/story/2018/9w5cyp

  1. 疾患特異的マクロファージの機能的多様性 佐藤 荘 みにれびゅう  Journal of Japanese Biochemical Society 91(4): 561-564 (2019) doi:10.14952/SEIKAGAKU.2019.910561

参考

  1. Microglial Adenosine Receptors: From Preconditioning to Modulating the M1/M2 Balance in Activated Cells Cells Volume 10 Issue 5 10.3390/cells10051124 Cells 2021, 10(5), 1124; https://doi.org/10.3390/cells10051124
  2. Mer regulates microglial/macrophage M1/M2 polarization and alleviates neuroinflammation following traumatic brain injury Journal of Neuroinflammation volume 18, Article number: 2 (2021) Published: 05 January 2021
  3. Regulation of Human Macrophage M1–M2 Polarization Balance by Hypoxia and the Triggering Receptor Expressed on Myeloid Cells-1 Front. Immunol., 07 September 2017 | https://doi.org/10.3389/fimmu.2017.01097
  4. Differential Roles of M1 and M2 Microglia in Neurodegenerative Diseases Yu Tang & Weidong Le Molecular Neurobiology volume 53, pages1181–1194 (2016)
  5. 特集 がん・免疫・代謝・発生におけるM1/M2分類を超えたマクロファージの機能 細胞工学 ; vol. 33 no.12 (2014)
  6. JSI Newsletter Vol.22 No.1 2018/10/18 日本免疫学会会報
  7. M1 and M2 macrophages derived fromTHP-1 cells differentially modulate the response of cancer cells to etoposide Genin et al. BMC Cancer (2015) 15:577 DOI 10.1186/s12885-015-1546-9
  8. Role of Microglial M1/M2 Polarization in Relapse and Remission of Psychiatric Disorders and Diseases Yutaka Nakagawa1 and Kenji Chiba2,* Pharmaceuticals (Basel). 2014 Dec; 7(12): 1028–1048. doi: 10.3390/ph7121028 PMCID: 
  9. Macrophages within NSCLC tumour islets are predominantly of a cytotoxic M1 phenotype associated with extended survival C. M. Ohri, A. Shikotra, R. H. Green, D. A. Waller, P. Bradding European Respiratory Journal 2009 33: 118-126; DOI: 10.1183/09031936.00065708