Recombinant human thioredoxin-1 becomes oxidized in circulation and suppresses bleomycin-induced neutrophil recruitment in the rat airway
Recombinant human thioredoxin-1 becomes oxidized in circulation and suppresses bleomycin-induced neutrophil recruitment in the rat airway
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DOI：
10.1080/10715760701487682
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发表时间：
2007-01-01
影响因子：
3.3
通讯作者：
Nakamura, Hajime
中科院分区：
文献类型：
--
作者：
Nakamura, Takayuki;Hoshino, Yuma;Nakamura, Hajime
硫氧还蛋白-1（TRX）是一种具有抗炎作用的氧化还原活性蛋白。本研究探讨了重组人TRX（rhTRX）抑制博莱霉素（BLM）诱导的大鼠持续性急性肺损伤模型中中性粒细胞募集的最佳给药方法及其机制。雄性Wister大鼠经气管内注射0.125 mg/kg BLM，第3-6天静脉注射rhTRX 8 mg/kg/d，采用3种方案：每日推注、每日3 h输注或连续输注96 h。与其他两种方法相比，只有rhTRX持续输注显著减少中性粒细胞浸润。BLM诱导的循环中性粒细胞L-选择素表达下调可被rhTRX抑制。氧化的rhTRX显示出与还原的rhTRX相当的效果，并且与血浆孵育或在血浆中循环的rhTRX超过99%被氧化。这些结果表明，rhTRX在循环中被氧化，rhTRX的持续输注抑制了气道中的中性粒细胞募集。
Thioredoxin-1 (TRX) is a redox-active protein with anti- inflammatory effects. This study investigated the optimal delivery method and the mechanisms of recombinant human TRX (rhTRX) to suppress neutrophil recruitment in a rat bleomycin (BLM)-induced sustained acute lung injury model. In male Wister rats intratracheally administered with 0.125 mg/kg BLM, 8 mg/kg/day rhTRX was intravenously administered on days 3-6 using one of three protocols: daily bolus injection, 3 h daily infusion or continuous infusion for 96 h. Only the continuous-infusion of rhTRX significantly reduced the neutrophil infiltration compared with the other two methods. The BLM-induced down-regulation of L-selectin expression on circulating neutrophils was inhibited by rhTRX. Oxidized rhTRX showed a comparable effect with reduced rhTRX and rhTRX incubated with plasma or circulating in plasma was more than 99% oxidized. These results suggest that rhTRX becomes oxidized in circulation and continuous infusion of rhTRX suppresses neutrophil recruitment in the airway.