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 diss emination of human immunodeficiency virus type-1 (HIV-1). HIV-1-tat, a viral gene product essential for HIV replication, has been shown to i nteract 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 umbi lical vein EC, Our results show that treatment of EC with HIV-tat indu ces 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 abolishe d the HIV-tat-dependent induction of all the adhesion molecules, indic ating that protein synthesis was required for induction. The effect of HIV-tat on expression of adhesion molecules was potentiated by tumor necrosis factor (INF), a well-known inducer of adhesion molecules, Lik e TNF, HIV-tat also enhanced the adhesion of human promyelomonocytic H L-60 cells to EC, and this effect was abolished by treatment with anti bodies either against HIV-tat or adhesion molecules. Our results thus indicate that the HIV-tat protein can activate human vascular EC to in duce the expression of various adhesion molecules that may play a role in the extravasation of HIV-infected cells, (C) 1997 by The American Society of Hematology.