JP2006505527A - 感染症の予防および治療 - Google Patents
感染症の予防および治療 Download PDFInfo
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- JP2006505527A JP2006505527A JP2004530234A JP2004530234A JP2006505527A JP 2006505527 A JP2006505527 A JP 2006505527A JP 2004530234 A JP2004530234 A JP 2004530234A JP 2004530234 A JP2004530234 A JP 2004530234A JP 2006505527 A JP2006505527 A JP 2006505527A
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Abstract
Description
ライノウイルスでの実験結果から、種々のライノウイルス(HRV菌株14および16)によるヒト上皮細胞の感染によって、酸性スフィンゴミエリナーゼの活性化(図1)およびセラミドの遊離(図2)が起こることが示されている。
HIVは、本質的にウイルスのgp120分子がCD4受容体に結合することによってヒト細胞に感染する。gp120がCD4に結合しない場合には、HIVによる細胞の感染は単に無効となる。gp120分子はgp41分子と共に、gp120が三量体として存在する、オリゴマー複合体を形成する。Tリンパ球上でのCD4分子へのgp120の結合によって、gp120のコンフォメーションが変化する;特に、可変ループのコンフォメーションが変化し、そのため、いわゆる補助受容体結合部位が露出する。gp120は、この結合部位を介して補助受容体、通常サイトカイン受容体CCR5またはCXCR4に結合する。全体で、14を超える異なる補助受容体が同定されているが、CCR5またはCXCR4のみがin vivoで非常に重要であると思われる。細胞内へのウイルスの取り込みは、CD4へのHIVの結合および更なる補助受容体を介して開始される(クラパム(Clapham)P.R.,マックナイト(McKnight)A.(2001).HIV−1 receptors and cell tropism.British Medical Bulletin 58:43−59)。
病原性細菌およびウイルスによる感染に対するセラミド豊富な膜プラットフォームの重要性が、緑膿菌(Pseudomonas aeruginosa)による哺乳動物細胞の感染の例で示された。緑膿菌(P. aeruginosa)を感染させた後に、酸性スフィンゴミエリナーゼの活性化およびセラミドの遊離が、Chang上皮細胞、WI−38線維芽細胞、ex vivo肺線維芽細胞、ex vivo培養気管上皮細胞の感染後にin vitroと、気管上皮細胞においてin vivoの両方で認められた。感染後のセラミドの遊離はラフトで起こり、ラフトは遊離したセラミドによって、より大きな膜プラットフォームに再編成される。緑膿菌(P. aeruginosa)による感染後、遊離したセラミドおよび酸性スフィンゴミエリナーゼは、新たに形成された膜プラットフォームにおいて局在化する。
Claims (18)
- 感染症および/またはその経過が感染により影響を受ける疾患を予防するため、かつ/または治療するための、酸性スフィンゴミエリナーゼの阻害剤および/またはこの酵素により触媒される反応の生成物、特にセラミドの阻害剤の使用。
- 前記阻害剤が、抗うつ薬、特に三環系および/または四環系抗うつ薬であることを特徴とする、請求項1に記載の使用。
- 前記抗うつ薬が、アミトリプチリンおよび/またはイミプラミンであることを特徴とする、請求項2に記載の使用。
- 前記阻害剤が、三環系および/または四環系抗うつ薬、特にアミトリプチリンおよび/またはイミプラミンから誘導される物質であることを特徴とする、前記各請求項のいずれかに記載の使用。
- 前記阻害剤が、デシプラミンおよび/またはFGF(線維芽細胞成長因子)および/またはそれから誘導される物質であることを特徴とする、前記各請求項のいずれかに記載の使用。
- 前記阻害剤が、抗体、特に中和抗体であることを特徴とする、前記各請求項のいずれかに記載の使用。
- 前記抗体が、酸性スフィンゴミエリナーゼに対するものであることを特徴とする、請求項6に記載の使用。
- 前記抗体が、セラミドに対するものであることを特徴とする、請求項6に記載の使用。
- 感染症および/またはその経過が感染により影響を受ける疾患を予防するため、かつ/または治療するための、セラミド豊富な膜プラットフォームの形成を抑制する物質の使用。
- 前記物質が、β−シクロデキストリン、ナイスタチンおよび/もしくはフィリピン並びに/またはそれから誘導される物質であることを特徴とする、請求項9に記載の使用。
- 前記感染症が、ウイルス、細菌、寄生虫および/または菌類感染症であることを特徴とする、前記各請求項のいずれかに記載の使用。
- 前記感染症が、エイズ、A型肝炎、ライノウイルス感染症、ロシア春夏脳炎(SSME)、風疹、インフルエンザ、結核、髄膜炎菌感染症および/またはマラリアであることを特徴とする、前記各請求項のいずれかに記載の使用。
- その経過が感染により影響を受ける前記疾患が、嚢胞性線維症であることを特徴とする、前記各請求項のいずれかに記載の使用。
- 前記感染症が、牛疫および/またはブタコレラであることを特徴とする、前記各請求項のいずれかに記載の使用。
- 三環系および/または四環系抗うつ薬、特にアミトリプチリンおよび/またはイミプラミンから誘導される少なくとも1種類の物質の有効量と、薬剤担体と、を含む医薬組成物。
- デシプラミン、FGF、β−シクロデキストリン、ナイスタチンおよび/もしくはフィリピン並びに/またはそれから誘導される少なくとも1種類の物質の有効量と、薬剤担体と、を含む医薬組成物。
- 酸性スフィンゴミエリナーゼに対するものである少なくとも1種類の抗体、特に中和抗体の有効量と、薬剤担体と、を含む医薬組成物。
- セラミドに対するものである少なくとも1種類の抗体、特に中和抗体の有効量と、薬剤担体と、を含む医薬組成物。
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Also Published As
Publication number | Publication date |
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AU2003255468B2 (en) | 2010-04-29 |
EP1531826B1 (de) | 2011-05-11 |
US7812015B2 (en) | 2010-10-12 |
US20110059949A1 (en) | 2011-03-10 |
DE10239531A1 (de) | 2004-03-04 |
WO2004017949A2 (de) | 2004-03-04 |
CA2497582A1 (en) | 2004-03-04 |
CA2497582C (en) | 2013-11-19 |
EP1531826A2 (de) | 2005-05-25 |
JP4733980B2 (ja) | 2011-07-27 |
US20050209219A1 (en) | 2005-09-22 |
ATE508749T1 (de) | 2011-05-15 |
CN1688316A (zh) | 2005-10-26 |
WO2004017949A3 (de) | 2004-04-29 |
CN100502875C (zh) | 2009-06-24 |
ES2366895T3 (es) | 2011-10-26 |
AU2003255468A1 (en) | 2004-03-11 |
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