炭毒素による致死の原因となる主な組織標的
Shihui Liu1, Yi Zhang, Mahtab Moayeri
1Microbial Pathogenesis Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. shliu@niaid.nih.gov
Nature
|September 3, 2013
まとめ
バシルス・アントラシスの毒素は,特定の細胞タイプを損傷することによって致死性を引き起こします. アントラックス致死毒素 (LT) は心臓および血管細胞を標的とし,エデマ毒素 (ET) は主に肝細胞 (肝細胞) に影響を及ぼします.
科学分野:
- 微生物学 微生物学とは
- 毒理学 毒理学 毒理学
- 病理生理学 病理生理学とは
背景:
- バシルス・アントラシスは,致死毒素 (LT) とエデマ毒素 (ET) の2つのエクソトキシンによって炭菌を引き起こす.
- これらの毒素の致死的な効果に責任を負う特定の宿主細胞の標的は,未だに特定されていません.
- 毛細血管形態生成タンパク質-2 (CMG2) は,これらの毒素の既知の受容体である.
研究 の 目的:
- 宿主死亡につながる炭病致死毒素 (LT) と腫毒素 (ET) が標的となる重要な細胞タイプを明らかにする.
- 炭毒素受容体CMG2が,異なる細胞タイプにおける毒素誘発による致死性を媒介する役割を調査する.
主な方法:
- 細胞型特異的なCMG2-nullとCMG2-発現するマウスの生成.
- これらの遺伝子組み換えマウスを,精製された炭病致死毒素 (LT) と腫毒素 (ET) で挑戦した.
- 特定の細胞タイプの毒素誘発死亡率への貢献を評価する.
主要な成果:
- LTによる致死には,心筋細胞と血管の滑らかな筋肉細胞の損傷が含まれます.
- ET誘発の致死性は,主に肝細胞への作用を通して媒介されます.
- 以前の仮説とは異なり,LTまたはETによる内皮細胞標的化は,死亡率に有意に寄与しない.
結論:
- Bacillus anthracisは,異なる重要な臓器系を協調的に損傷することによって宿主の致死性を誘発するために,LTとETを使用します.
- LTとETは,異なる細胞タイプのトロピズムを示し,致命的な効果のために別々の重要な細胞集団をターゲットにします.
- 内皮細胞は炭毒素による致死性の主要な標的ではない.
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