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RI+ Cells1
*
Division of Clinical Immunology and Allergy, University of Naples Federico II, Naples, Italy;
Department of Medicine, Second University of Naples, Naples, Italy;
Department of Clinical and Biological Sciences, University of Insubria School of Medicine, Varese, Italy; and Advanced Biotechnology Center, Genoa, Italy
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 ß-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
Fc
RI+ 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 ß-chemokine homologue that influences the directional
migration of human FcRI+ cells and the expression of
surface receptor CCR3 on these cells.
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