Pathogen moleculoar pattern recognition mechanisms inside and outsied of the blood vessel

• Project/Area Number: 22591064
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hematology
• Research Institution: Saga University
• Principal Investigator: FUKUDOME Kenji 佐賀大学, 医学部, 准教授 (50284625)
• Co-Investigator(Kenkyū-buntansha): KIMOTO Masao 佐賀大学, 医学部, 教授 (40153225) ; TSUNEYOSHI Naoko 佐賀大学, 医学部, 客員研究員 (80336114)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 血液免疫学 / モノクローナル抗体 / 粗面小胞体 / ストレスシグナル / TLR4 / TLR / 血管内皮 / 敗血症 / アゴニスト / 抗体

Research Abstract

We demonstrated that sensitive LPS-recogition by macrophadese was due to the strong TLR4-signal transduction induced by raft-formation in the cells carring memebrane-associated CD14. The signal transduction was not so effective in CD14-negative cells such as B cells; however, it was significant to induce some responses. We discovered that LPS-tolerance was resulted by loss of antigen-presenting function in B cells differenciated by LPS-stimulation in the absence of antigen.

Research Products

• [Journal Article] nhibition of antibody production in vivo by pre-stimulation of Toll-like receptor 4 before antigen priming is caused by defective B cell priming and not impairment in antigen presentation (2013)
  • Author(s): Nurlaely MR, Fukudome K, Tsuneyoshi N, Bahrun U, Tsukamoto H, Yanagibashi T, Nagai Y, Takatsu K, Ohta S, Kimoto M.
  • Journal Title: Int Immunol Volume: 25(2) Pages: 117-128
  • Peer Reviewed
• [Journal Article] Multiple potential regulatory sites of TLR4 activation induced by LPS as revealed by novel inhibitory human TLR4 mAbs (2013)
  • Author(s): Tsukamoto H, Fukudome K, Takao S, Tsuneyoshi N, Ihara H, Ikeda Y, Kimoto M
  • Journal Title: Int Immunol Volume: 190(1) Pages: 195-204
  • Peer Reviewed
• [Journal Article] Inhibition of antibody production in vivo by pre-stimulation of Toll-like receptor 4 before antigen priming is caused by defective B-cell priming and not impairment in antigen presentation. (2013)
  • Author(s): Rachmawati NM
  • Journal Title: International Immunology Volume: 2 Pages: 117-28
  • Peer Reviewed
• [Journal Article] Reduced surface expression of TLR4 by a V254I point mutation accounts for the low lipopolysaccharide responder phenotype of BALB/c B cells. (2013)
  • Author(s): Tsukamoto H
  • Journal Title: Journal of Immunology Volume: 190
  • Peer Reviewed
• [Journal Article] Multiple potential regulatory sites of TLR4 activation induced by LPS as revealed by novel inhibitory human TLR4 mAbs. (2012)
  • Author(s): Tsukamoto H
  • Journal Title: International Immunology Volume: 8 Pages: 495-506
  • Peer Reviewed
• [Journal Article] Activated protein C utilizes the angiopoietin/Tie2 axis to promote endothelial barrier function (2010)
  • Author(s): Minhas N, Xue M, Fukudome K, Jackson CJ
  • Journal Title: FASEB J Volume: 24(3) Pages: 873-81
  • Peer Reviewed
• [Journal Article] Blocking endothelial protein C receptor (EPCR) accelerates thrombus development in vivo (2010)
  • Author(s): Centelles MN, Puy C, Lopez-Sagaseta J, Fukudome K, Montes R, Hermida J
  • Journal Title: Thromb Haemost Volume: 03(6) Pages: 1239-44
  • Peer Reviewed
• [Journal Article] Organotypic culture of human bone marrow adipose tissue (2010)
  • Author(s): Uchihashi K, Aoki S, Shigematsu M, Kamochi N, Sonoda E, Soejima H, Fukudome K, Sugihara H, Hotokebuchi T, Toda S
  • Journal Title: Pathol Int Volume: 60(4) Pages: 259-67
  • NAID: 10029331372
  • Peer Reviewed
• [Journal Article] Lipopolysaccharide-binding protein-mediated Toll-like receptor 4 dimerization enables rapid signal transduction against lipopolysaccharide stimulation on membrane-associated CD14-expressing cells (2010)
  • Author(s): Tsukamoto H, Fukudome K, Takao S, Tsuneyoshi N, Kimoto M
  • Journal Title: Int Immunol Volume: 22(4) Pages: 271-80
  • NAID: 10027392279
  • Peer Reviewed
• [Journal Article] Lipopolysaccharide-binding protein-mediated Toll-like receptor 4 dimerization enables rapid signal transduction against lipopolysaccharide stimulation on membrane-associated CD14-expressing cells. (2010)
  • Author(s): Tsukamoto H
  • Journal Title: Int Immunol. Volume: 22(4) Pages: 271-280
  • Peer Reviewed
• [Journal Article] Endotoxin tolerance attenuates airway allergic inflammation in model mice by suppression of the T-cell stimulatory effect of dendritic cells. (2010)
  • Author(s): Matsushita H
  • Journal Title: Int Immunol. Volume: 22(9) Pages: 739-747
  • Peer Reviewed
• [Journal Article] Organotypic culture of human bone marrow adipose tissue. (2010)
  • Author(s): Uchihashi K
  • Journal Title: Pathol Int. Volume: 60(4) Pages: 259-267
  • Peer Reviewed
• [Journal Article] Lopez-Sagaseta J, Fukudome K, Montes R, Hermida J. : Blocking endothelial protein C receptor (EPCR) accelerates thrombus development in vivo. (2010)
  • Author(s): Centelles MN
  • Journal Title: Thromb Haemost. Volume: 103(6) Pages: 1239-1244
  • Peer Reviewed
• [Journal Article] Activated protein C utilizes the angiopoietin/Tie2 axis to promote endothelial barrier function. (2010)
  • Author(s): Minhas N
  • Journal Title: FASEB J. Volume: 24(3) Pages: 873-881
  • Peer Reviewed
• [Presentation] Inhibition of antibody production in vivo by pre-stimulation of Toll-like receptor 4 before antigen priming is caused by defective B-cell priming and not impairment in antigen presentation. (2012)
  • Author(s): Rachmawati NM
  • Organizer: 日本免疫学会
  • Place of Presentation: 神戸
• [Presentation] Inhibition of primary but not secondary humoral immune responses by pre-injection of an agonistic anti-TLR4/MD-2 antibody. (2011)
  • Author(s): Rachmawati NM, Fukudome K, Tsuneyoshi N, Uleng B, Ohta S, Kimoto M
  • Organizer: 第40回日本免疫学会
  • Place of Presentation: 千葉市
  • Year and Date: 2011-11-28
• [Presentation] Inhibition of primary but not secondary humoral immune responses by pre-injection of an agonistic anti-TLR4/MD-2 antibody (2011)
  • Author(s): Rachmawati NM
  • Organizer: 日本免疫学会
  • Place of Presentation: 幕張メッセ(千葉県)
  • Year and Date: 2011-11-28
• [Presentation] Agonistic anti-TLR4 monoclonal antibodies function as immunoadjuvants (2010)
  • Author(s): Rachmawati NM, Uleng B, Fukudome K, Kimoto M
  • Organizer: 第14回国際免疫学会議
  • Place of Presentation: 神戸市
  • Year and Date: 2010-08-27
• [Presentation] Lipopolysaccharidebindingprotein-mediated Toll-like receptor 4 dimerization enables rapid signal transduction against lipopolysaccharide stimulation on membrane-associated CD14-expressing cells (2010)
  • Author(s): Tsukamoto H, Fukudome K, Takao S, Tsuneyoshi N, Kimoto M.
  • Organizer: 第14回国際免疫学会議
  • Place of Presentation: 神戸市
  • Year and Date: 2010-08-27
• [Presentation] Agonistic anti-TLR4 monoclonal antibodies function as immunoadjuvants. (2010)
  • Author(s): Rachmawati NM
  • Organizer: 第14回国際免疫学会議
  • Place of Presentation: 神戸市
  • Year and Date: 2010-08-27
• [Presentation] Lipopolysaccharide-bindingprotein-mediated Toll-like receptor 4 dimerization enables rapid signal transduction against lipopolysaccharide stimulation on membrane-associated CD14-expressing cells. (2010)
  • Author(s): Tsukamoto H
  • Organizer: 第14回国際免疫学会議
  • Place of Presentation: 神戸市
  • Year and Date: 2010-08-27
• [Remarks] ホームページ
  • URL: http://www.biomol.med.saga-u.ac.jp/immunol/index.htm