Human immunodeficiency virus transactivator protein (Tat) stimulates chemotaxis, calcium mobilization, and activation of human polymorphonuclear leukocytes: Implications for Tat-mediated pathogenesis
Human immunodeficiency virus transactivator protein (Tat) stimulates chemotaxis, calcium mobilization, and activation of human polymorphonuclear leukocytes: Implications for Tat-mediated pathogenesis
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DOI：
10.1086/317597
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发表时间：
2000-12-01
影响因子：
6.4
通讯作者：
Albini, A
中科院分区：
文献类型：
--
作者：
Benelli, R;Barbero, A;Albini, A
人类免疫缺陷病毒(HIV)反式激活蛋白(TAT)的胞外活性包括诱导血管生成和刺激单核细胞迁移。在体内，多形核白细胞(PMNL)，主要是中性粒细胞，响应TAT的反应迅速入侵并启动新血管的形成。在体外，TAT对PMNL具有趋化作用并诱导钙(Ca~(2+))动员，在精氨酸-甘氨酸-天冬氨酸或碱性结构域具有失活取代的TAT蛋白仍具有诱导PMNL迁移的活性，而TAT多肽将迁移和Ca~(2+)动员活性映射到一个富含半胱氨酸的核心区。以前被描述为TAT“趋化素样”区域(多肽CysL(24-51))。TAT和CysL(24-51)肽还可诱导PMNL产生超氧化物和释放血管生成因子IL-X和血管内皮生长因子，CysL(24-51)不诱导内皮细胞迁移，但在体内具有血管生成作用。这些数据表明，TAT在PMNL上的活性是由其趋化素样区域介导的，Tar对PMNL的募集与血管生成有关。
The extracellular activities of the human immunodeficiency virus (HIV) transactivator protein (Tat) include induction of angiogenesis and stimulation of monocyte migration, Here it is shown that polymorphonuclear leukocytes (PMNL), mostly neutrophils, rapidly invade in response to Tat in vivo and initiate the formation of new vessels, In vitro, Tat was chemotactic for PMNL and induced calcium (Ca2+) mobilization, Tat proteins with inactivating substitutions in the arginine-glycine-aspartic acid or basic domain were still active in inducing PMNL migration, whereas Tat peptides mapped the migration and Ca2+ mobilization activity to a cysteine-rich core domain, previously described as a Tat "chemokine-like" region (peptide CysL(24-51)). Tat and the CysL(24-51) peptide also induced PMNL superoxide production and the release of the angiogenic factors interleukin-X and vascular endothelial growth factor from PMNL, CysL(24-51) did not induce endothelial cell migration but was angiogenic in vivo. These data indicate that the Tat activity on PMNL is mediated by its chemokine-like region and that PMNL recruitment by Tar is linked to angiogenesis.