Tat Protein Is an HIV-1-Encoded β-Chemokine Homolog That Promotes Migration and Up-Regulates CCR3 Expression on Human FcεRI+ Cells1

Tat Protein Is an HIV-1-Encoded β-Chemokine Homolog That Promotes Migration and Up-Regulates CCR3 Expression on Human FcεRI+ Cells1
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Tat 蛋白是一种 HIV-1 编码的 β-趋化因子同源物,可促进人 FcεRI+ 细胞迁移并上调 CCR3 表达1

DOI:
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发表时间:
2000
影响因子:
4.4
通讯作者:
G. Marone
G. Marone
中科院分区:
医学2区
文献类型:
--
作者:
A. de Paulis;R. De Palma;Luisa Di Gioia;Maria Carfora;N. Prevete;G. Tosi;R. Accolla;G. Marone

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人嗜碱性细胞和肥大细胞表达趋化因子受体CCR3,该受体结合趋化因子eotaxin和RANTES。HIV-1 Tat蛋白是一种有效的趋化剂,用于嗜碱性细胞和肺肥大细胞,这些细胞来自对HIV-1和HIV-2血清抗体阴性的健康人。该蛋白在嗜碱性细胞和肥大细胞中诱导快速和短暂的Ca2+内流,类似于β趋化因子。该蛋白既不诱导人嗜碱性细胞和肥大细胞释放组胺,也不增加il -3刺激嗜碱性细胞分泌组胺。用抗ccr3抗体预孵育FcεRI+细胞可阻断Tat蛋白的趋化活性。用抗Tat (aa 1-86)单抗预孵育Tat可阻断Tat诱导的迁移。相比之下,特异于基本区(aa 46-60)的mAb并没有抑制Tat蛋白的趋化作用。这种蛋白或eotaxin使嗜碱性细胞对随后的自体或异源刺激脱敏。Tat蛋白预处理嗜碱性细胞可上调CCR3 mRNA水平和CCR3受体的表面表达。该蛋白是第一个被发现的hiv -1编码的β-趋化因子同源物,它影响人类FcεRI+细胞的定向迁移和这些细胞表面受体CCR3的表达。
Human basophils and mast cells express the chemokine receptor CCR3, which binds the chemokines eotaxin and RANTES. HIV-1 Tat protein is a potent chemoattractant for basophils and lung mast cells obtained from healthy individuals seronegative for Abs to HIV-1 and HIV-2. Tat protein induced a rapid and transient Ca2+ influx in basophils and mast cells, analogous to β-chemokines. Tat protein neither induced histamine release from human basophils and mast cells nor increased IL-3-stimulated histamine secretion from basophils. The chemotactic activity of Tat protein was blocked by preincubation of FcεRI+ cells with anti-CCR3 Ab. Preincubation of Tat with a mAb anti-Tat (aa 1–86) blocked the migration induced by Tat. In contrast, a mAb specific for the basic region (aa 46–60) did not inhibit the chemotactic effect of Tat protein. Tat protein or eotaxin desensitized basophils to a subsequent challenge with the autologous or the heterologous stimulus. Preincubation of basophils with Tat protein up-regulated the level of CCR3 mRNA and the surface expression of the CCR3 receptor. Tat protein is the first identified HIV-1-encoded β-chemokine homologue that influences the directional migration of human FcεRI+ cells and the expression of surface receptor CCR3 on these cells.
巨细胞病毒编码的β趋化因子促进宿主中单核细胞相关的病毒血症。
DOI: 10.1073/pnas.96.19.10881
发表时间: 1999
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