Macrophage inflammatory responses to amorphous silica particles

• Project/Area Number: 24590158
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Environmental pharmacy
• Research Institution: Tohoku University
• Principal Investigator: NAKAYAMA Masafumi 東北大学, 学際科学フロンティア研究所, 准教授 (20453582)
• Co-Investigator(Kenkyū-buntansha): OGASAWARA Kouetsu 東北大学, 加齢医学研究所, 教授 (30323603)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: シリカ粒子 / マクロファージ / 炎症 / 肺炎 / 貪食

Outline of Final Research Achievements

Although amorphous silica particles are used in a wide variety of products such as pharmaceuticals and foods, the immunotoxicity of these particles is not fully understood. In this study, we addressed the relationship between the size of amorphous silica and the inflammatory activity. Of note, 30 nm-1000 nm diameter silica particles induced macrophage lysosomal destabilization, cell death, and IL-1β secretion at markedly higher levels than did 3000 nm-10000 nm silica particles. Consistent with in vitro results, intra-tracheal administration of 30 nm silica particles into mice caused more severe lung inflammation than that of 3000 nm silica particles. Taken together, these results suggest that silica particle size impacts immune responses, with submicron amorphous silica particles inducing higher inflammatory responses than silica particles over 1000 nm in size.

Research Products

• [Journal Article] Antigen presentation by MHC-dressed cells. (2015)
  • Author(s): Nakayama M
  • Journal Title: Front. Immunol. Volume: 672 Pages: 1-5
  • DOI: 10.3389/fimmu.2014.00672
  • Peer Reviewed / Open Access
• [Journal Article] Effect of silica particle size on macrophage inflammatory responses (2014)
  • Author(s): Kusaka T, Nakayama M, Nakamura K, Ishimiya M, Furusawa E, Ogasawara K
  • Journal Title: PLoS One Volume: 9 Issue: 3 Pages: 597-606
  • DOI: 10.1371/journal.pone.0092634
  • Peer Reviewed / Open Access
• [Journal Article] NKG2D+ IFN-γ+ CD8+ T cells are responsible for palladium allergy. (2014)
  • Author(s): Kawano M, Nakayama M, Aoshima Y, Nakamura K, Ono M, Nishiya T, Nakamura S, Takeda Y, Dobashi A, Takahashi A, Endo M, Ito A, Ueda K, Sato N, Higuchi S, Kondo T, Hashimoto S, Watanabe M, Watanabe M, Takahashi T, Sasaki K, Nakamura M, Sasazuki T, Narushima T, Suzuki R, Ogasawara K.
  • Journal Title: PLoS One. Volume: 9 Issue: 2 Pages: 1-12
  • DOI: 10.1371/journal.pone.0086810
  • Peer Reviewed / Open Access
• [Journal Article] 細菌感染におけるペア型受容体の役割 (2014)
  • Author(s): 中山勝文、小笠原康悦
  • Journal Title: Surgery Frontier Volume: 21 Pages: 41-45
• [Journal Article] NK cell-fratricide: dynamic crosstalk between NK cells and tumor cells (2013)
  • Author(s): Nakamura K, Nakayama M, Kawano M, Ishii T, Harigae H, Ogasawara K
  • Journal Title: Oncoimmunology Volume: 2
  • Peer Reviewed
• [Journal Article] Interruption of dendritic cell-mediated TIM-4 signaling induces regulatory T cells and promotes skin allograft survival (2013)
  • Author(s): Yeung M, McGrath M, Nakayama M, Shimizu T, Boenisch O, Magee CN, Abdoli R, Akiba H, Ueno T, Turka L, and Najafian N
  • Journal Title: J Immunol Volume: 191 Issue: 8 Pages: 4447-4455
  • DOI: 10.4049/jimmunol.1300992
  • Peer Reviewed
• [Journal Article] Fratricide of NK cells dressed with tumor-derived NKG2D ligand (2013)
  • Author(s): Nakamura K, Nakayama M, Kawano M, Amagai R, Ishii T, Harigae H, and Ogasawara K
  • Journal Title: Proc Natl Acad Sci USA Volume: 110 Issue: 23 Pages: 9421-9426
  • DOI: 10.1073/pnas.1300140110
  • Peer Reviewed
• [Journal Article] Inhibitory receptor PIR-B is exploited by Staphylococcus aureus for virulence (2012)
  • Author(s): Nakayama M, Kurokawa K, Nakamura K, Lee BL, Sekimizu K, Kubagawa H, Hiramatsu K, Yagita H, Okumura K, Takai T, Underhill DM, Aderem A, Ogasawara K.
  • Journal Title: J Immunol Volume: 189 Issue: 12 Pages: 5903-5911
  • DOI: 10.4049/jimmunol.1201940
  • Peer Reviewed
• [Presentation] Inhibitory receptor PIR-B is exploited by Staphylococcus aureus for virulence (2013)
  • Author(s): Nakayama M, Underhill DM, Nakamura K, Yagita H, Okumura K, Takai T, Aderem A, Ogasawara K
  • Organizer: 第42回 日本免疫学会総会
  • Place of Presentation: 幕張
• [Presentation] Natural killer cell death mediated by NKG2D-trogocytosis (2013)
  • Author(s): Nakamura K, Nakayama M, Kawano M, Ishii T, Harigae H, Ogasawara K
  • Organizer: 55th Annual Meeting-American Society of Hematology
  • Place of Presentation: New Orleans, LA, USA
• [Presentation] Trogocytosis-mediated generation of regulatory MHCII-dressed NK cells (2012)
  • Author(s): Nakayama M, Takeda K, Nakamura K, and Ogasawara K
  • Organizer: 第41回 日本免疫学会総会
  • Place of Presentation: 神戸
• [Presentation] Effect of particle size of silica on macrophage inflammatory responses (2012)
  • Author(s): Kusaka T, Nakayama M, Nakamura K, and Ogasawara K
  • Organizer: 第41回 日本免疫学会総会
  • Place of Presentation: 神戸
• [Remarks] 東北大学加齢医学研究所ホームページニュース「細菌と免疫系との新たな攻防メカニズムを解明しました」
  • URL: http://www.idac.tohoku.ac.jp/ja/activities/info/news/20121221/index.html