Human immunodeficiency virus-1-tat protein induces the cell surface expression of endothelial leukocyte adhesion molecule-1, vascular cell adhesion molecule-1, and intercellular adhesion molecule-1 in human endothelial cells.
Human vascular endothelial cells (EC) have been implicated in the dissemination of human immunodeficiency virus type-1 (HIV-1). HIV-1-tat, a viral gene product essential for HIV replication, has been shown to interact with different cell types, altering their growth and inducing gene expression. In the present report, we have examined the effect of HIV-tat on the expression of various adhesion molecules in human umbilical vein EC. Our results show that treatment of EC with HIV-tat induces the cell surface expression of intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and endothelial leukocyte adhesion molecule-1 in a time- and dose-dependent manner. Cycloheximide abolished the HIV-tat-dependent induction of all the adhesion molecules, indicating that protein synthesis was required for induction. The effect of HIV-tat on expression of adhesion molecules was potentiated by tumor necrosis factor (TNF), a well-known inducer of adhesion molecules. Like TNF, HIV-tat also enhanced the adhesion of human promyelomonocytic HL-60 cells to EC, and this effect was abolished by treatment with antibodies either against HIV-tat or adhesion molecules. Our results thus indicate that the HIV-tat protein can activate human vascular EC to induce the expression of various adhesion molecules that may play a role in the extravasation of HIV-infected cells.
Dhawan
S
S
Division of Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD, USA.
Puri
R K
RK
Kumar
A
A
Duplan
H
H
Masson
J M
JM
Aggarwal
B B
BB
D003513:Cycloheximide / Q000494:pharmacology; D004357:Drug Synergism; D019040:E-Selectin / Q000096:biosynthesis*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D005434:Flow Cytometry; D015696:Gene Products, tat / Q000494:pharmacology*; D015497:HIV-1; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D013050:Spectrometry, Fluorescence; D013499:Surface Properties; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis*; D054322:tat Gene Products, Human Immunodeficiency Virus
D019040:E-Selectin; D015696:Gene Products, tat; D011500:Protein Synthesis Inhibitors; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D054322:tat Gene Products, Human Immunodeficiency Virus; D018799:Intercellular Adhesion Molecule-1; D003513:Cycloheximide