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病原体の上皮細胞接着に対する初期応答が感染感受性を規定する

Research Project

Project/Area Number 15659239
Research Category

Grant-in-Aid for Exploratory Research

Allocation TypeSingle-year Grants
Research Field 膠原病・アレルギー・感染症内科学
Research InstitutionNara Medical University

Principal Investigator

喜多 英二  奈良県立医科大学, 医学部, 教授 (90133199)

Co-Investigator(Kenkyū-buntansha) 三笠 桂一  奈良県立医科大学, 医学部, 教授 (80209725)
前田 光一  奈良県立医科大学, 医学部, 講師 (30295795)
Project Period (FY) 2003 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2005: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2004: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2003: ¥2,300,000 (Direct Cost: ¥2,300,000)
Keywordsrespiratory infection / syndecan shedding / S.penumoniae / innate immunity / pneumonia / MMP-7 / S.pneumoniae / 細菌性肺炎 / 気道感染 / surfactant / chemokine / cytokine / opsonin activity / シンデカン / 粘膜炎症 / ケモカイン / 微生物接着 / 肺炎連鎖球菌 / サーファクタント
Research Abstract

呼吸器感染における気道内炎症反応の初期応答解明を目的として、年齢層の異なるマウスとsyndecan-1 knockout(SYN-1KO)マウスにおける肺炎連鎖球菌気管内感染モデルを用いた解析から、以下のことを明らかにした。
1)若齢マウス(4週齢以下)では、気道上皮に幼若な上皮細胞の割合が多く、肺炎連鎖球菌感染で強いMMP-7活性化とsyndecan-1 sheddingを誘発し、結果として好中球主体の顕著な炎症応答を招き、浸潤好中球による気道傷害をきたす。
2)高齢マウス(12週齢以上)では、気道上皮に幼若な上皮細胞の割合が低いため、肺炎連鎖球菌感染によるsyndecan-1 sheddingレベルは低いが、同時に上皮細胞でのsufactant産生量も少ないため、炎症応答は弱いが、肺でのクリアランスが低下し、MMP-7の活性化が低く、組織修復が弱い。
3)6〜9週齢マウスでは、肺炎連鎖球菌感染後に一過性のsyndecan-1 sheddingと単球主体の炎症反応を認め、MMP-7活性化は感染後期に顕著で、急速な炎症終結と組織修復が認められた。
4)SYN-1KOマウスは強毒株感染に対し単球主体の炎症反応と感染後期のMMP-7活性化を認め、強い抵抗性を示した。感染時に精製SYN-1 ectodomainをSYN-1KOマウス気管内投与すると、好中球主体の炎症反応を呈し感受性が著しく亢進した。
以上の結果から、呼吸器感染において、気道上皮におけるsyndecanの遊離強度と持続期間が、その後の肺内炎症強度と質的特性を規定することが、確認された。この研究成果から、syndecan-1遊離制御が呼吸器感染症における抗生剤治療の補助療法として、有効になる可能性が示唆された。

Report

(3 results)
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • Research Products

    (15 results)

All 2006 2005 2004 2003 Other

All Journal Article (9 results) Book (3 results) Publications (3 results)

  • [Journal Article] Favorable modification of macrolide-resistant Streptococcus pneumoniae infection in the lung by a 14-membered ring macrolide2006

    • Author(s)
      Yasuki Yasuda, Kei Kasahara, Eiji Kita, et al.
    • Journal Title

      J.Infect.Dis. (in press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Subcutaneous vaccination of Mycobacterium bovis Bacillus Calmette-Guerin (BCG) attenuates allergic inflammation in a murine model of asthma2005

    • Author(s)
      Ito T, Hamada K, Suzaki Y, Matsui N, Kita E, Kimura H.
    • Journal Title

      Allergy International 54

      Pages: 601-609

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Macrolide resistance of Streptococcus pneumoniae isolated during long term macrolide therapy : A difference between erythromycin and clarithromycin2005

    • Author(s)
      Kasahara K, Kita E, Maeda K, et al.
    • Journal Title

      J.Infect.Chemother. 11

      Pages: 112-114

    • NAID

      10015526209

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Clonal dissemination of macrolide resistant penicillin susceptible serotype 3 and penicillin resistant Taiwan 19F-14 and 23F-15 Streptococcus pneumoniae in Japan.2005

    • Author(s)
      Kasahara K., Mikasa K., Konishi M., Maeda K., Kita E.et al.
    • Journal Title

      J.Clin.Microbiol. 43

      Pages: 1640-1645

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Macrolide resistance of Streptococcus pneumoniae isolated during long term macrolide therapy : A difference between erythromycin and clarithromycin2005

    • Author(s)
      Kasahara K, Kita K, et al.
    • Journal Title

      J.Infect.Chemother In press

    • NAID

      10015526209

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Clonal dissemination of macrolide resistant penicillin susceptible serotype 3 and penicillin resistant Taiwan 19F-14 and 23F-15 Streptococcus pneumoniae in Japan2005

    • Author(s)
      Kasahara K, Kita E, et al.
    • Journal Title

      J.Clin.Microbiol. In press

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Long-term azithromycin therapy for three patients with chronic lower respiratory tract infections.2004

    • Author(s)
      Kasahara K., Mikasa K., Konishi M., Maeda K., Kita E.et al.
    • Journal Title

      J.Infect.Chemother. 10

      Pages: 42-45

    • NAID

      10016521124

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Long-term azithromycin therapy for three patients with chronic lower respiratory tract infections2004

    • Author(s)
      Kasahara K., Kita E.et al.
    • Journal Title

      J.Infect.Chemother 10

      Pages: 42-45

    • NAID

      10016521124

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Syndecan shedding from epithelial cells affects host defense against respiratory infection.2003

    • Author(s)
      Kita E.
    • Journal Title

      Int.Cong.Ser. 1257

      Pages: 21-26

    • Related Report
      2005 Annual Research Report
  • [Book] Modulation of respiratory inflammation and defense by macrolides In : Antibiotics as Anti-Inflammatories. (B.K.Rubin & J.Tamaoki, eds)2004

    • Author(s)
      Mikasa K.
    • Total Pages
      12
    • Publisher
      BioSciences, Birkhaeuser Publishing Ltd.
    • Related Report
      2005 Annual Research Report
  • [Book] Antibiotics as Anti-Inflammatories2004

    • Author(s)
      Mikasa K., Kasahara K., Kita E.
    • Total Pages
      14
    • Publisher
      B.K.Rubin & J.Tamaoki
    • Related Report
      2004 Annual Research Report
  • [Book] Syndecan shedding from epithelial cells affects host defense against respiratory infection2003

    • Author(s)
      Kita E.
    • Total Pages
      5
    • Publisher
      Cong.Ser.
    • Related Report
      2004 Annual Research Report
  • [Publications] Kita E.: "Syndecan shedding from epithelial cells affects host defense against respiratory infection"Int.Cong.Ser.. 1257. 21-26 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kasahara K.: "Long-term azithromycin therapy for three patients with chronic lower respiratory tract infections"J.Infect. Chemother. 10. 42-45 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Mikasa K.: "Modulation of respiratory inflammation and defense by macrolides In : Antibiotics as Anti-Inflammatories. (B.K.Rubin & J.Tamaoki, eds)"BioSciences, Birkhaeuser Publishing Ltd.. 12 (2004)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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