Abstract
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 Ca(2+) influx in basophils and mast cells, analogous to beta-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 FcepsilonRI(+) 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 beta-chemokine homologue that influences the directional migration of human FcepsilonRI(+) cells and the expression of surface receptor CCR3 on these cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Antibodies, Monoclonal / pharmacology
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Basophils / immunology
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Basophils / metabolism*
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Calcium / metabolism
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Calcium Signaling / immunology
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Cell Migration Inhibition
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Cell Movement / immunology*
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Chemokine CCL11
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Chemokines, CC / antagonists & inhibitors
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Chemokines, CC / genetics
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Chemokines, CC / immunology
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Chemokines, CC / physiology*
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Chemotaxis, Leukocyte / immunology
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Cytokines / antagonists & inhibitors
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Cytokines / pharmacology
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Epitopes / immunology
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Gene Expression Regulation / immunology
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Gene Products, tat / antagonists & inhibitors
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Gene Products, tat / genetics
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Gene Products, tat / immunology
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Gene Products, tat / physiology*
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HIV-1 / genetics
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HIV-1 / physiology*
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Histamine Release / immunology
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Humans
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Lung / cytology
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Lung / immunology
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Mast Cells / immunology
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Mast Cells / metabolism*
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RNA, Messenger / biosynthesis
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Receptors, CCR3
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Receptors, Chemokine / biosynthesis*
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Receptors, Chemokine / genetics
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Receptors, HIV / biosynthesis
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Receptors, IgE / biosynthesis*
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Sequence Homology, Amino Acid
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Up-Regulation / immunology
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tat Gene Products, Human Immunodeficiency Virus
Substances
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Antibodies, Monoclonal
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CCL11 protein, human
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CCR3 protein, human
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Chemokine CCL11
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Chemokines, CC
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Cytokines
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Epitopes
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Gene Products, tat
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RNA, Messenger
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Receptors, CCR3
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Receptors, Chemokine
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Receptors, HIV
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Receptors, IgE
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tat Gene Products, Human Immunodeficiency Virus
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Calcium