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急性呼吸障害症候群における表面活性剤特異タンパク質の損傷
C S Baker1, T W Evans, B J Randle
1Cell Biology Unit, National Heart and Lung Institute, Imperial College School of Medicine, London, UK.
Lancet (London, England)
|April 27, 1999
まとめ
急性呼吸器障害症候群 (ARDS) は,表面活性物質タンパク質を損傷し,中性粒子の弾性酵素 (neutrophil elastase) による可能性が高い. このin-vivoダメージは,ARDS患者のための現在の表面活性剤治療の有効性を制限する可能性があります.
科学分野:
- 肺内医学 肺内医学 肺内医学
- クリティカルケアでは,
- バイオケミストリー バイオケミストリー
背景:
- 急性呼吸器障害症候群 (ARDS) は,高い死亡率と特定の治療法のない重症な状態です.
- ARDSにおける中性粒子の活性化は,肺損傷と表面活性物質の機能障害につながる.
- 中性粒子のエラスタゼは表面活性物質タンパク質を分解し,治療効果を潜在的に制限する可能性があります.
研究 の 目的:
- ARDS患者における表面活性剤特異性タンパク質のインビボ損傷を調査する.
- 中性粒子のエラスターゼがARDS肺における表面活性物質タンパク質の損傷に責任があるかどうかを判断する.
主な方法:
- 肺表面活性物質のサンプルは,18人のARDS患者と6人の健康な対照群から,ブロンコアルベオラ洗浄で採取されました.
- タンパク質分離はSDS-PAGEを用いて行われました.
- モノクローナル抗体 (E8) を用いたウェスタン・ブラッティングで,表面活性剤特異タンパク質A (SP-A) を特定した.
主要な成果:
- 18人のARDS患者のうち14人が,対照群と異なるSP-A損傷の証拠を示した.
- 損傷したSP-Aは,対照群の正常ジマー (66 kDa) と比較して,変異した分子量帯 (55 kDa,30-36 kDa,36-40 kDa) を示した.
- 観察された損傷パターンは,中性粒子のエラスタゼによるSP-Aのインビトロ割れに似ている.
結論:
- 表面活性剤特異のタンパク質は,おそらくタンパク質分解によって,ARDS患者の肺に直接損傷します.
- 中性粒子の産物によるこの継続的な損傷は,ARDSにおける治療的表面活性物質に対する限られた反応を説明する可能性がある.
- 表面活性剤と抗プロテアゼの併用療法により,ARDSの治療結果が改善される可能性があります.
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