Document 0133
 DOCN  M9650133
 TI    HIV-1-Tat modulates the function of monocytes and alters their
       interactions with microvessel endothelial cells. A mechanism of HIV
       pathogenesis.
 DT    9605
 AU    Lafrenie RM; Wahl LM; Epstein JS; Hewlett IK; Yamada KM; Dhawan S;
       Laboratory of Developmental Biology, National Institute of Dental;
       Research, Bethesda, MD 20892, USA.
 SO    J Immunol. 1996 Feb 15;156(4):1638-45. Unique Identifier : AIDSLINE
       MED/96164596
 AB    Monocytes are major targets of HIV infection in patients with AIDS. In
       vitro infection of monocytes with HIV is associated with increased
       expression of beta 2 integrins, which increases both monocyte
       aggregation and monocyte/endothelial adhesion as well as monocyte
       metalloproteinase (MMP-9) expression. Treatment of primary monocytes
       with soluble HIV-Tat protein mimicked many of the properties of HIV
       infection of monocytes. Tat treatment up-regulated the expression of the
       beta 2 integrins, which was associated with the formation of large
       aggregates of monocytes and increased adhesion to endothelial
       monolayers. Treatment of monocytes with Tat increased their adhesion to
       both untreated and TNF-alpha-treated endothelial monolayers, and
       adhesion was inhibited by inclusion of anti-beta 2 and anti-ICAM-1 Abs.
       The increased adhesion of activated monocytes was accompanied by
       substantial disruption of the endothelial monolayers, with retraction or
       detachment of individual endothelial cells. Tat treatment of monocytes
       up-regulated the synthesis and release of the protease MMP-9, providing
       a potential mechanism to explain endothelial cell/basement membrane
       detachment. Thus, extracellular Tat is capable of activating monocytes
       even in the absence of HIV infection. Our studies demonstrate that many
       of the effects of HIV infection on monocyte homotypic and heterotypic
       adhesion, protease secretion, and disruption of the endothelium can be
       mimicked by treatment with HIV-Tat protein alone. These results suggest
       a mechanism where monocytes could be inappropriately activated by
       HIV-Tat, secreted by HIV-infected cells, causing them to extravasate
       into underlying tissues and ultimately contribute to tissue damage as
       seen during the progression of AIDS.
 DE    Cell Adhesion  Cell Aggregation  Cells, Cultured
       Collagenases/GENETICS/METABOLISM  Endothelium, Vascular/*IMMUNOLOGY
       Gene Expression Regulation, Viral  Gene Products, tat/*IMMUNOLOGY  Human
       HIV-1/*IMMUNOLOGY/PATHOGENICITY  Monocytes/*IMMUNOLOGY  Receptors,
       Cytoadhesin/*METABOLISM  RNA, Messenger/GENETICS  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).