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 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.
de Paulis
A
A
Division of Clinical Immunology and Allergy, University of Naples Federico II, Naples, Italy.
De Palma
R
R
Di Gioia
L
L
Carfora
M
M
Prevete
N
N
Tosi
G
G
Accolla
R S
RS
Marone
G
G
D000328:Adult; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001491:Basophils / Q000276:immunology / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000276:immunology; D002464:Cell Migration Inhibition; D002465:Cell Movement / Q000276:immunology*; D054413:Chemokine CCL11; D019742:Chemokines, CC / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000939:Epitopes / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology; D015696:Gene Products, tat / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006636:Histamine Release / Q000276:immunology; D006801:Humans; D008168:Lung / Q000166:cytology / Q000276:immunology; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D054397:Receptors, CCR3; D019707:Receptors, Chemokine / Q000096:biosynthesis* / Q000235:genetics; D015728:Receptors, HIV / Q000096:biosynthesis; D017455:Receptors, IgE / Q000096:biosynthesis*; D017386:Sequence Homology, Amino Acid; D015854:Up-Regulation / Q000276:immunology; D054322:tat Gene Products, Human Immunodeficiency Virus
D000911:Antibodies, Monoclonal; C515456:CCL11 protein, human; C515350:CCR3 protein, human; D054413:Chemokine CCL11; D019742:Chemokines, CC; D016207:Cytokines; D000939:Epitopes; D015696:Gene Products, tat; D012333:RNA, Messenger; D054397:Receptors, CCR3; D019707:Receptors, Chemokine; D015728:Receptors, HIV; D017455:Receptors, IgE; D054322:tat Gene Products, Human Immunodeficiency Virus; D002118:Calcium