Thioredoxin, a redox enzyme released in infection and inflammation, is a unique chemoattractant for neutrophils, monocytes, and T cells.
Thioredoxin, a redox enzyme released in infection and inflammation, is a unique chemoattractant for neutrophils, monocytes, and T cells.
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DOI：
10.1084/jem.189.11.1783
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发表时间：
1999-06-07
期刊：
影响因子：
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通讯作者：
Ghezzi P
中科院分区：
文献类型：
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作者：
Bertini R;Howard OM;Dong HF;Oppenheim JJ;Bizzarri C;Sergi R;Caselli G;Pagliei S;Romines B;Wilshire JA;Mengozzi M;Nakamura H;Yodoi J;Pekkari K;Gurunath R;Holmgren A;Herzenberg LA;Herzenberg LA;Ghezzi P
硫氧还蛋白（Trx）是一种普遍存在的细胞内蛋白质二硫键氧化还原酶，具有CXXC活性位点，可在激活后由各种细胞类型释放。我们在这里表明，Trx是单核细胞，多形核白细胞和T淋巴细胞的趋化性，无论是在体外的标准微Boyden室迁移试验和在体内的小鼠气囊模型。Trx对所有白细胞群体的趋化作用的效力在纳摩尔范围内，与已知的趋化因子相当。然而，Trx不增加细胞内Ca 2+，其活性不受百日咳毒素抑制。因此，Trx的趋化作用不同于已知的趋化因子，因为它不依赖于G蛋白。活性位点半胱氨酸的突变导致趋化活性的丧失，表明后者是由Trx的酶活性介导的。Trx也占了人类T淋巴细胞病毒（HTLV）-1感染细胞释放的趋化活性的一部分，这是抑制与抗Trx抗体孵育。由于Trx的产生是由氧化剂诱导的，它代表了氧化应激和炎症之间的联系，这是特别感兴趣的，因为循环Trx水平在炎症性疾病和HIV感染中升高。
Thioredoxin (Trx) is a ubiquitous intracellular protein disulfide oxidoreductase with a CXXC active site that can be released by various cell types upon activation. We show here that Trx is chemotactic for monocytes, polymorphonuclear leukocytes, and T lymphocytes, both in vitro in the standard micro Boyden chamber migration assay and in vivo in the mouse air pouch model. The potency of the chemotactic action of Trx for all leukocyte populations is in the nanomolar range, comparable with that of known chemokines. However, Trx does not increase intracellular Ca2+ and its activity is not inhibited by pertussis toxin. Thus, the chemotactic action of Trx differs from that of known chemokines in that it is G protein independent. Mutation of the active site cysteines resulted in loss of chemotactic activity, suggesting that the latter is mediated by the enzyme activity of Trx. Trx also accounted for part of the chemotactic activity released by human T lymphotropic virus (HTLV)-1–infected cells, which was inhibited by incubation with anti-Trx antibody. Since Trx production is induced by oxidants, it represents a link between oxidative stress and inflammation that is of particular interest because circulating Trx levels are elevated in inflammatory diseases and HIV infection.