Tat protein is an HIV-1-encoded beta-chemokine homolog that promotes migration and up-regulates CCR3 expression on human Fc epsilon RI+ cells

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.