赤血球フェロポルチンは,細胞内鉄の蓄積,血解,マラリアのリスクを軽減する
De-Liang Zhang1, Jian Wu2, Binal N Shah3
1Section on Human Iron Metabolism, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Science (New York, N.Y.)
|March 31, 2018
まとめ
鉄エクスポーターフェロポルチン (FPN) は赤血球 (RBC) をマラリアから保護する. アフリカの集団で見つかった特定のFPN変異 (Q248H) は,重度のマラリアに対する保護を提供しており,FPNの疾患耐性における役割を強調しています.
科学分野:
- 血液学
- 寄生虫学
- 遺伝学
背景:
- マラリア感染は 鉄分調節を妨害し 貧血を引き起こします
- 逆説的に 鉄の補給はマラリアを悪化させるが 根本的なメカニズムは不明だ
- 赤血球 (赤血球) はマラリアの病原産と鉄代謝に中心的な役割を果たします.
研究 の 目的:
- マラリア感染時の赤血球における鉄エクスポーターフェロポルチン (FPN) の役割を調査する.
- FPNの機能と遺伝的変異が マラリアの重症度と宿主防御にどのように影響するかを理解する.
主な方法:
- ネズミの赤血球細胞におけるFPNの条件付きの遺伝子消去
- 赤血球におけるFPN発現と活性の分析
- ヒトのFPN変異 (Q248H) と,FPNの分解とマラリア予防への影響の調査.
主要な成果:
- FPNは赤血球に豊富に存在し,その活動は鉄補給によって抑制されます.
- エリソイド細胞のFPNを削除すると,マラリアに感染したマウスの鉄過負荷,細胞損傷,血液溶解,死亡率の増加が起こります.
- 人間のFPN Q248H変異はヘプシジン誘発の分解を防止し,重度のマラリアに対する保護を与えます.
- マラリアの圧力によるアフリカ人集団におけるFPN Q248Hの陽性選択が示唆されている.
結論:
- フェロポルチン (FPN) は,酸化ストレスとマラリアに対する赤血球の重要な保護作用をします.
- FPN Q248H変異は重症マラリアに対する有意な保護を与え,マラリアが流行する地域で選択されています.
- FPNの役割を理解することで,マラリアの病原性や潜在的な治療戦略の洞察が得られます.
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