Exogenous tat protein activates central nervous system-derived endothelial cells.
Tat protein, an HIV gene product known to be secreted extracellularly, was tested to determine its role in the dissemination of HIV into the central nervous system (CNS). Tat was shown to activate human CNS-derived endothelial cells (CNS-EC) by the increase in the expression of E-selectin, the synthesis of IL-6, and the secretion of plasminogen activator inhibitor-1 (PAI-1). Tat also functioned synergistically with tumor necrosis factor alpha (TNF). AIDS brains stained for tat in situ, demonstrated positive cells. These data suggest that secreted tat protein may increase leukocyte binding, and alter the blood-brain barrier permeability to enhance dissemination of HIV-infected cells into the CNS.
Hofman
F M
FM
Department of Pathology, University of Southern California School of Medicine, Los Angeles 90033.
Dohadwala
M M
MM
Wright
A D
AD
Hinton
D R
DR
Walker
S M
SM
D000163:Acquired Immunodeficiency Syndrome / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002478:Cells, Cultured; D002490:Central Nervous System / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004357:Drug Synergism; D019040:E-Selectin; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects; D015696:Gene Products, tat / Q000494:pharmacology*; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D054322:tat Gene Products, Human Immunodeficiency Virus
D015815:Cell Adhesion Molecules; D019040:E-Selectin; D015696:Gene Products, tat; D015850:Interleukin-6; D017395:Plasminogen Activator Inhibitor 1; D014409:Tumor Necrosis Factor-alpha; D054322:tat Gene Products, Human Immunodeficiency Virus