ヘパリンは,マスト細胞の特定の粒子のプロテアゼの貯蔵に不可欠です
D E Humphries1, G W Wong, D S Friend
1Department of Medicine, Boston University School of Medicine, and VA Medical Center, Massachusetts 02130, USA. Humphries.Donald_E@BOSTON.VA.GOV
Nature
|August 31, 1999
まとめ
ヘパリンは,重要なグリコサミノグリカンであり,マスト細胞のプロテアゼレベルを調節する. この研究ではヘパリンが検出されました.
科学分野:
- バイオケミストリー バイオケミストリー
- 免疫学 免疫学とは
- 分子生物学は分子生物学である.
背景:
- ヘパリンは,哺乳類のどこにでも存在するグリコサミノグリカンであり,主にマスト細胞の顆粒に含まれています.
- 広範な研究にもかかわらず,ヘパリンの正確な生理学的役割は未だに曖昧である.
- マスト細胞は,アレルギー反応や炎症に関与する重要な免疫細胞です.
研究 の 目的:
- 哺乳類におけるヘパリンの生理学的機能を調査する.
- マスト細胞プロテアゼの調節におけるヘパリンの役割を決定する.
- ヘパリンがマスト細胞のプロテアゼ含有量に影響を与えるメカニズムを解明する.
主な方法:
- N-デアセチラゼ/N-スルフォトランスフェラーゼ-2遺伝子を破壊することによって,完全硫化ヘパリンが欠けているトランスジェニックマウスの生成.
- トランス遺伝子マウスの骨格筋におけるマスト細胞粒子の分析.
- トランスジェニックマウスの骨髄から得られたマスト細胞の培養と分析.
主要な成果:
- ヘパリンを欠いたトランスゲン性マスト細胞は,メタクロマティック粒子の欠乏を示した.
- これらのマスト細胞は,特定のプロテアゼ (mMCP-4,mMCP-5,mMC-CPA) を蓄えることができなかったが,mMCP-7を保持していた.
- トランスジェニックマウスから培養されたマスト細胞は,高いプロテアーストランスクリプトレベルにもかかわらず,減少したmMCP-5およびmMC-CPA発現を示した.
結論:
- ヘパリンは,マスト細胞内の特定の陽性電荷タンパク質の適切な貯蔵に不可欠です.
- ヘパリンは,翻訳後のメカニズムで特定のタンパク質のレベルを調節する.
- この発見は,マスト細胞生物学とプロテアゼ調節の重要な側面を明らかにします.
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