Human immunodeficiency virus type 1 TAT protein induces adhesion molecule expression in astrocytes.
AIDS encephalitis is a frequent consequence of CNS HIV infection, especially in children. One of its many characteristics is a leukocyte infiltrate that is believed to contribute to the production of cytokines, chemokines and neurotoxic factors resulting in CNS damage. Entry of such leukocytes into the CNS is mediated in part by the expression of adhesion molecules by blood - brain barrier (BBB) endothelial cells. Expression of these proteins by astrocytes, the other main component of the BBB, also serves to target leukocytes to the CNS parenchyma. We now demonstrate that HIV-1-derived Tat, a soluble protein secreted by infected cells, induced astrocyte VCAM-1 and ICAM-1 expression in a dose- and time-dependent manner. The functional role of Tat in monocyte binding in vitro was also demonstrated. These data suggest that the presence of extracellular Tat may be a significant factor in the trafficking of HIV-infected and inflammatory cells into the CNS via its effect on adhesion molecule expression by astrocytes.
Woodman
S E
SE
Department of Pathology, Albert Einstein College of Medicine Bronx, New York, NY 10461, USA.
Benveniste
E N
EN
Nath
A
A
Berman
J W
JW
D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism*; D015152:Blotting, Northern; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D003470:Culture Media / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D015696:Gene Products, tat / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D015483:HIV Antibodies / Q000378:metabolism; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology; D012333:RNA, Messenger / Q000032:analysis; D020298:U937 Cells; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D054322:tat Gene Products, Human Immunodeficiency Virus
D003470:Culture Media; D015696:Gene Products, tat; D015483:HIV Antibodies; D012333:RNA, Messenger; D019010:Vascular Cell Adhesion Molecule-1; D054322:tat Gene Products, Human Immunodeficiency Virus; D018799:Intercellular Adhesion Molecule-1