Document 0428
 DOCN  M9650428
 TI    Mechanisms for the transendothelial migration of HIV-1-infected
       monocytes into brain.
 DT    9605
 AU    Nottet HS; Persidsky Y; Sasseville VG; Nukuna AN; Bock P; Zhai QH;
       Sharer LR; McComb RD; Swindells S; Soderland C; Gendelman HE; Department
       of Pathology, Eppley Institute for Cancer and Allied; Disease,
       University of Nebraska Medical Center, Omaha 68198, USA.
 SO    J Immunol. 1996 Feb 1;156(3):1284-95. Unique Identifier : AIDSLINE
       MED/96144356
 AB    HIV-1 penetration of the brain is a pivotal event in the
       neuropathogenesis of AIDS-associated dementia. The establishment of
       productive viral replication or up-regulation of adhesion molecule
       expression on brain microvascular endothelial cells (BMVEC) could permit
       entry of HIV into the central nervous system. To investigate the
       contribution of both, we inoculated primary human BMVEC with high titer
       macrophage-tropic HIV-1 or cocultured them with virus-infected
       monocytes. In both instances, BMVEC failed to demonstrate productive
       viral replication. Cell to cell contact between monocytes and
       microvascular endothelium resulted in E-selectin expression on BMVEC.
       BMVEC. cocultured with LPS-activated HIV-infected monocytes expressed
       even higher levels of E-selectin and vascular cell adhesion molecule-1
       (VCAM-1). Transwell assays supported a role of soluble factors, from
       virus-infected monocytes, for the induction of adhesion molecules on
       BMVEC. To verify the in vivo relevance of these findings, levels of
       adhesion molecules were compared with those of proinflammatory cytokines
       and HIV-1 gene products in brain tissue of AIDS patients with or without
       encephalitis and HIV-seronegative controls. E-Selectin, and to a lesser
       degree VCAM-1, paralleled the levels of HIV-1 gene products and
       proinflammatory cytokines in brain tissue of subjects with encephalitis.
       Most importantly, an association between macrophage infiltration and
       increased endothelial cell adhesion molecules was observed in
       encephalitic brains. Monocyte binding to encephalitic brain tissue was
       blocked with Abs to VCAM-1 and E-selectin. These data, taken together,
       suggest that HIV entry into brain is, in part, a consequence of the
       ability of virus-infected and immune-activated monocytes to induce
       adhesion molecules on brain endothelium.
 DE    Base Sequence  Brain/BLOOD SUPPLY/*VIROLOGY  Cell Adhesion  Cell
       Movement/*IMMUNOLOGY  Cells, Cultured  E-Selectin/BIOSYNTHESIS/DRUG
       EFFECTS  Endothelium, Vascular/*METABOLISM  Human  HIV
       Infections/ETIOLOGY/IMMUNOLOGY/PATHOLOGY  HIV-1/*PATHOGENICITY
       Macrophage Activation  Molecular Sequence Data
       Monocytes/IMMUNOLOGY/*VIROLOGY  Support, Non-U.S. Gov't  Support, U.S.
       Gov't, P.H.S.  Vascular Cell Adhesion Molecule-1/BIOSYNTHESIS/DRUG
       EFFECTS/  IMMUNOLOGY  JOURNAL ARTICLE

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