超大型のフォン・ウィレブランド因子繊維は,スチアストレスの下での無傷な内皮細胞層への光線性Staphylococcus aureus粘着を媒介する
Karin I Pappelbaum1, Christian Gorzelanny, Sandra Grässle
1Experimental Dermatology, Department of Dermatology, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.
Circulation
|May 31, 2013
まとめ
ウルトラ・ラージ・フォン・ウィレブランド因子 (ULVWF) は,健康な心臓組織への黄金球菌の初期粘着を媒介し,感染症性心内炎の重要なステップである. ULVWF形成を標的とする治療法は,この感染症を予防する有望な結果を示しています.
科学分野:
- 心血管生物学 心血管生物学
- 微生物学 微生物学とは
- 血液学 ヘマトロジ
背景:
- Staphylococcus aureus感染性エンドカルディティスは,以前に心疾患がなかった場合もしばしば発生します.
- 完ぺきな心臓内膜への最初の細菌の粘着のメカニズムは十分に理解されていません.
研究 の 目的:
- 形質学的に無傷な内心部にStaphylococcus aureusが最初接着する分子のメカニズムを解明する.
- 細菌の粘着を媒介する超大フォン・ウィレブランド因子 (ULVWF) の役割を調査する.
主な方法:
- 発光性S. aureusで活性化されたヒト内皮細胞を高シール条件下でインビトロ perfusion した.
- VWF消去変異体とヘパリンを用いたフロー実験.
- 粘着因子に対するバクテリアの消去変異体の分析.
- 野生型およびVWFノックアウトマウスの体内内微鏡検査.
主要な成果:
- ULVWFは,S. aureusの内皮細胞への結合の95%を媒介した.
- VWFのA型ドメインと細菌壁のテイコ酸が結合に関与しています.
- 血小板と血清は,ULVWF媒介による粘着性を高めました.
- ADAMTS13はバクテリアの結合を減少させたが,ULVWFは依然としてバクテリアを結合させた.
- VWFのノックアウトマウスは,体内で細菌の粘着性が著しく低下したことを示した.
結論:
- ULVWFは,完ぺきな内皮のS. aureus内心炎の初期病原性段階において極めて重要です.
- ヘパリンまたはADAMTS13でULVWF形成をターゲットにすることは,潜在的な治療戦略を提供します.
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