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Exogenous tat protein activates human endothelial cells [see comments]
FM Hofman, AD Wright, MM Dohadwala, F Wong-Staal and SM Walker
Department of Pathology, University of Southern California School of
Medicine, Los Angeles 90033.
tat protein, a human immunodeficiency virus (HIV) gene product that
functions as a transactivator for HIV replication, is known to be secreted
extracellularly by infected cells. To determine the potential role of tat
in the dissemination of HIV into extravascular tissue, this protein was
examined for its ability to activate human endothelial cells. The results
show that tat does indeed stimulate endothelial cells. This is evidenced by
their expression of the endothelial- leukocyte adhesion molecules,
E-selectin, critical for the initial binding of leukocytes to the blood
vessel wall, and their increased synthesis of interleukin-6 (IL-6), a
cytokine known to enhance endothelial cell permeability. Furthermore, tat
acts synergistically with low concentrations of tumor necrosis factor-alpha
to enhance IL-6 secretion. These data suggest that extracellular tat
protein secreted or released into the microenvironment may contribute
significantly to the determination of specific sites of leukocyte binding
to blood vessels, to transmigration into tissue, and to eventual
dissemination of HIV-infected cells or free virions into tissue.
Volume 82,
Issue 9,
pp. 2774-2780,
11/01/1993
Copyright © 1993 by The American Society of Hematology
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