Activation of platelet toll-like receptors and its clinical significance

• Project/Area Number: 20591153
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hematology
• Research Institution: Ehime University
• Principal Investigator: HATO Takaaki Ehime University, 医学部附属病院, 准教授 (30172943)
• Co-Investigator(Renkei-kenkyūsha): YAMANOUCHI Jun 愛媛大学, 医学部附属病院, 講師 (10423451) ; YASUKAWA Masaki 愛媛大学, 医学系研究科, 教授 (60127917)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2008: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 血小板 / TOLL-like receptor / 自然免疫 / 細菌感染症 / Toll-like receptor / インテグリン / GPIIb-IIIa / 敗血症 / 感染症 / 免疫学

Research Abstract

We examined the role of toll-like receptors (TLR) on the platelet surface. Stimulation of platelet TLR with bacterial components promoted the platelet adhesive response through another platelet receptor. Serum from patients with sepsis, a severe bacterial infection, promoted the platelet adhesive response through platelet TLR. These results indicate that the linkage between platelets and various pathogens promotes the platelet adhesive activity, suggesting a crucial role of platelets on the host defense mechanism.

Research Products

• [Journal Article] Vasodilator-stimulated phosphoprotein (VASP) phosphorylation assay for platelet response to cilostazol. (2011)
  • Author(s): Yamanouchi J, Hato T, Niiya T, Nakagawa K, Kumon Y, Fujiwara H, Yakushijin Y, Yasukawa M
  • Journal Title: Platelets 22 Pages: 135-142
  • Peer Reviewed
• [Journal Article] 巨核球に形態異常を呈したCMLの一症例 (2011)
  • Author(s): 新家敏之、吉岡ゆき、岡本康二、坂東史郎、村瀬光春、西宮達也、東太地、羽藤高明、安川正貴、大澤春彦
  • Journal Title: 愛媛臨検技会誌 30 Pages: 79-85
  • Peer Reviewed
• [Journal Article] Vasodilator-stimulated phosphoprotein (VASP) phosphorylation assay for platelet response to cilostazol (2011)
  • Author(s): Yamanouchi J, Hato T, Niiya T, Nakagawa K, Kumon Y, Fujiwara H, Yakushijin Y, Yasukawa M
  • Journal Title: Platelets Volume: 22 Pages: 135-142
  • Peer Reviewed
• [Journal Article] Derivative (1 ; 18)(q10 ; q10) in essential thrombocythemia. (2010)
  • Author(s): Azuma T, Yamanouchi J, Inoue K, Kohno M, Narumi H, Fujiwara H, Yakushijin Y, Hato T, Yasukawa M.
  • Journal Title: Cancer Genet Cytogenet 199 Pages: 62-64
  • Peer Reviewed
• [Journal Article] プレドニゾロンが著効した後天性凝固第V因子インヒビターの症例 (2010)
  • Author(s): 山之内純、羽藤高明
  • Journal Title: 日本血栓止血学会誌 21 Pages: 391-394
  • NAID: 10026711733
  • Peer Reviewed
• [Journal Article] Derivative (1;18)(q10;q10) in essential thrombocythemia (2010)
  • Author(s): Azuma T, Yamanouchi J, Inoue K, Kohno M, Narumi H, Fujiwara H, Yakushijin Y, Hato T, Yasukawa M
  • Journal Title: Cancer Genet Cytogenet Volume: 199 Pages: 62-64
  • Peer Reviewed
• [Journal Article] プレドニゾロンが著効した後天性凝固第V因子インヒビターの症例 (2010)
  • Author(s): 山之内純、羽藤高明
  • Journal Title: 日本血栓止血学会誌 Volume: 21 Pages: 391-394
  • NAID: 10026711733
  • Peer Reviewed
• [Journal Article] Compound heterozygous mutations in the PROS1 gene responsible for quantitative and qualitative protein S deficiency. (2009)
  • Author(s): Yamanouchi J, Hato T, Tamura T, Fujiwara H,, Yakushijin Y, Yasukawa M
  • Journal Title: Int J Hemato, 1 90 Pages: 537-539
  • NAID: 10026109711
  • Peer Reviewed
• [Journal Article] Identification of a novel epitope derived from CML66 which is recognized by anti-leukaemia cytotoxic T lymphocytes. (2009)
  • Author(s): Suemori K, Fujiwara H, Ochi T, Azuma T, Yamanouchi J, Narumi H, Yakushijin Y, Hato T, Yasukawa M
  • Journal Title: Br J Haematol 46 Pages: 115-118
  • Peer Reviewed
• [Journal Article] Clinical significance of co-expression of CD21 and LFA-1 in B-cell lymphoma. (2009)
  • Author(s): Tanimoto K, Yakushijin Y, Fujiwara H, Otsuka M, Ohshima K, Sugita A, Sakai A, Hato T, Hasegawa H, Yasukawa M
  • Journal Title: Int J Hematol 89 Pages: 497-507
  • NAID: 10025161350
  • Peer Reviewed
• [Journal Article] Aurora-A kinase: a novel target of cellular immunotherapy for leukemia. (2009)
  • Author(s): Ochi T, Fujiwara H, Suemori K, Azuma T, Yakushijin Y, Hato T, Kuzushima K, Yasukawa M
  • Journal Title: Blood 113 Pages: 66-74
  • Peer Reviewed
• [Journal Article] The role of zinc finger protein 521/early hematopoietic zinc finger protein in erythroid cell differentiation. (2009)
  • Author(s): Matsubara E, Sakai I, Yamanouchi J, Fujiwara H, Yakushijin Y, Hato T, Shigemoto K, Yasukawa M
  • Journal Title: J Biol Chem 284 Pages: 3480-3487
  • Peer Reviewed
• [Journal Article] ノカルジアによる多発性筋膿瘍を併発した後天性血友病 (2009)
  • Author(s): 山之内純、阿部圭見、東太地、成見弘、藤原弘、薬師神芳洋、羽藤高明、安川正貴
  • Journal Title: 臨床血液 50 Pages: 495-498
  • NAID: 10024960378
  • Peer Reviewed
• [Journal Article] 治療中に病的骨折を起こした骨原発悪性リンパ腫 (2009)
  • Author(s): 村上雄一、山之内純、東太地、池田祐一、成見弘、藤原弘、薬師神芳洋、羽藤高明、安川正貴
  • Journal Title: 臨床血液 50 Pages: 187-191
  • NAID: 10024959249
  • Peer Reviewed
• [Journal Article] Compound heterozygous mutations in the PROS1 gene responsible for quantitative and qualitative protein S deficiency (2009)
  • Author(s): Yamanouchi J., et al.
  • Journal Title: International Journal of Hematology 90 Pages: 537-539
  • Peer Reviewed
• [Journal Article] The role of zinc finger protein 521/early hematopoietic zinc finger protein in erythroid cell differentiation (2009)
  • Author(s): Matsubara E., et al.
  • Journal Title: Journal of Biological Chemistry 284
  • Peer Reviewed
• [Journal Article] Aurora-A kinase : a novel target of cellular immunotherapy for leukemia (2009)
  • Author(s): Ochi T., et al.
  • Journal Title: Blood 113 Pages: 66-74
  • Peer Reviewed
• [Journal Article] Identification of an epitope derived from CML66, a novel tumor-associated antigen expressed broadly in human leukemia, recognized by human leukocyte antigen-A*2402- restricted cytotoxic T lymphocytes. (2008)
  • Author(s): Suemori K, Fujiwara H, Ochi T, Azuma T, Yamanouchi J, Narumi H, Yakushijin Y, Hato T, Hasegawa H, Yasukawa M
  • Journal Title: Cancer Sci 99 Pages: 1414-1419
  • NAID: 10024008706
  • Peer Reviewed
• [Journal Article] Cooperative role of the membrane-proximal and -distal residues of the integrin β3 cytoplasmic domain in regulation of talin-mediated αIIbβ3 activation. (2008)
  • Author(s): Hato T, Yamanouchi J, Tamura T, Yakushijin Y, Sakai I, Yasukawa M
  • Journal Title: J Biol Chem 283 Pages: 5662-5668
  • Peer Reviewed
• [Journal Article] Cooperative role of the membrane-proximal and -distal residues of the integrin β3 cytoplasmic domain in regulation of talin-mediated αIIbβ3 activation. (2008)
  • Author(s): Hato T, Yamanouchi J, Tamura T, Yakushijin Y, Sakai I, Yasukawa M
  • Journal Title: Journal of Biological Chemistry 283 Pages: 5662-5668
  • Peer Reviewed
• [Journal Article] Identification of an epitope derived from CML66, a novel tumor-associated antigen expressed broadly in human leukemia, recognized by human leukocyte antigen-A*2402-restricted cytotoxic T lymphocytes. (2008)
  • Author(s): Suemori K, Fujiwara H, Ochi T, Azuma T, Yamanouchi J, Narumi H, Yakushijin Y, Hato T, Hasegawa H, Yasukawa M
  • Journal Title: Cancer Science 99 Pages: 1414-1419
  • NAID: 10024008706
  • Peer Reviewed
• [Presentation] The β taildomain (βTD) in the integrin b3 subunit regulates αIIbβ3 activation (2010)
  • Author(s): Yamanouchi J, Hato T, Fujiwara H, Yakushijin Y, Yasukawa M
  • Organizer: 第72回日本血液学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2010-09-24
• [Presentation] The β tail domain (βTD) in the integrinβ3 subunit regulates αIIbβ3 activation. (2010)
  • Author(s): 山之内純、羽藤高明、藤原弘、薬師神芳洋、安川正貴
  • Organizer: 第72回日本血液学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2010-09-24
• [Presentation] Integrin β3 membrane-proximal and -distal residues cooperatively regulate talin-mediated αIIbβ3 activation. (2009)
  • Author(s): Yamanouchi J, Hato T, Fujiwara H, Yakushijin Y, Yasukawa M
  • Organizer: The 22^<nd> Congress of the International Society on Thrombosis and Haemostasis
  • Place of Presentation: Boston, USA
  • Year and Date: 2009-07-15
• [Presentation] Integrin β3 membrane-proximal and -distal residues cooperatively regulate talin-mediated αIIbβ3 activation (2009)
  • Author(s): Yamanouchi J., et al.
  • Organizer: The 22^<nd> Congress of International Society on Thrombosis and Haemostasis
  • Place of Presentation: 米国 ボストン市
  • Year and Date: 2009-07-15
• [Presentation] Compound heterozygous mutations in the PROS1 gene responsible for quantitative and qualitative Protein S deficiency (2009)
  • Author(s): Yamanouchi J, Hato T, Fujiwara H, Yakushijin Y, Yasukawa M
  • Organizer: The 22^<nd> Congress of the International Society on Thrombosis and Haemostasis
  • Place of Presentation: Boston, USA
  • Year and Date: 2009-07-13
• [Presentation] Toll-like receptorsを介した血小板インテグリンαIIbβ3の活性化 (2009)
  • Author(s): 山之内純、羽藤高明
  • Organizer: 第32回日本血栓止血学会学術集会
  • Place of Presentation: 北九州
  • Year and Date: 2009-06-05
• [Presentation] Integrin β3 membrane-proximal and -distal residues cooperatively regulate talin-mediated αIIbβ3 activation. (2008)
  • Author(s): Yamanouchi J, Hato T, Fujiwara H, Yakushijin Y, Yasukawa M
  • Organizer: The 50^<th> ASH annual meeting
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2008-12-06
• [Presentation] Integrin β3 membrane-proximal and -distal residues cooperatively regulatetalin-mediated αIIbβ3 activation (2008)
  • Author(s): Yamanouchi, J, Hato T, Fujiwara H Yakushijin Y, Yasukawa M
  • Organizer: The 50^<th> Annual meeting of American Society of Hematology
  • Place of Presentation: San Francisco (USA)
  • Year and Date: 2008-12-06
• [Presentation] テグリンβ3細胞内領域の膜近位部位と遠位部位はαIIbβ3の活性化を協調して制御してしる (2008)
  • Author(s): 羽藤 高明, 山之内 純, 田村 達司郎, 薬師神 芳洋, 酒井 郁也, 藤原 弘, 安川 正貴
  • Organizer: 第70回日本血液学会総会
  • Place of Presentation: 京都
  • Year and Date: 2008-10-11
• [Presentation] インテグリンβ3細胞内領域の膜近位部位と遠位部位はαIIbβ3の活性化を協調制御している (2008)
  • Author(s): 羽藤高明、山之内純、田村達司郎、薬師神芳洋、酒井郁也、藤原弘、安川正貴
  • Organizer: 第70回日本血液学会総会
  • Place of Presentation: 京都
  • Year and Date: 2008-10-10
• [Book] 輸血・血液型検査(今日の臨床検査) (2009)
  • Author(s): 羽藤高明
  • Publisher: 南江堂
• [Book] HLA検査今日の臨床検査 (2009)
  • Author(s): 羽藤高明
  • Publisher: 南江堂