A. De Paulis et al., Tat protein is an HIV-1-encoded beta-chemokine homolog that promotes migration and up-regulates CCR3 expression on human Fc epsilon RI+ cells, J IMMUNOL, 165(12), 2000, pp. 7171-7179
Human basophils and mast cells express the chemokine receptor CCR3, which b
inds the chemokines eotaxin and RANTES. HIV-1 Tat protein is a potent chemo
attractant for basophils and lung mast cells obtained from healthy individu
als seronegative for Abs to HIV-1 and HIV-2. Tat protein induced a rapid an
d transient Ca2+ influx in basophils and mast cells, analogous to beta -che
mokines, Tat protein neither induced histamine release from human basophils
and mast cells nor increased IL-3-stimulated histamine secretion from baso
phils, The chemotactic activity of Tat protein was blocked by preincubation
of Fc epsilon RI+ cells with anti-CCR3 Ab. Preincubation of Tar with a mAb
anti-Tat (aa 1-86) blocked the migration induced by Tar. In contrast, a mA
b specific for the basic region (aa 46-60) did not inhibit the chemotactic
effect of Tat protein. Tar protein or eotaxin desensitized basophils to a s
ubsequent challenge with the autologous or the heterologous stimulus. Prein
cubation 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 i
dentified HTV-1-encoded beta -chemokine homologue that influences the direc
tional migration of human Fc epsilon RI+ cells and the expression of surfac
e receptor CCR3 on these cells.