Document 0141
 DOCN  M94A0141
 TI    Upregulation of human immunodeficiency virus-1 in chronically infected
       monocytic cell line by both contact with endothelial cells and
       cytokines.
 DT    9412
 AU    Fan ST; Hsia K; Edgington TS; Department of Immunology, Scripps Research
       Institute, La Jolla,; CA 92037.
 SO    Blood. 1994 Sep 1;84(5):1567-72. Unique Identifier : AIDSLINE
       MED/94348081
 AB    Cells of monocytic lineage (Mo) persistently infected with human
       immunodeficiency virus (HIV) have been suspected to be a major reservoir
       for in vivo transmission of virus to susceptible target cells. Cellular
       events and mechanisms that upregulate viral gene expression in such
       cells are important issues. Because the traffic of such cells is central
       to biodistribution of HIV, we have explored the impact of interaction of
       endothelium with HIV-1-infected U1 promonocytic cells. Coculturing of U1
       with human umbilical endothelial cells (HUVEC) for 24 to 72 hours in the
       absence of stimulation induced HIV-1 p24 biosynthesis significantly.
       Antibody-blocking experiments indicated that CD11/CD18 integrins play a
       role in upregulation of HIV expression elicited by interaction with
       HUVEC. Engagement of CD11b/CD18 by adherence of U1 to surfaces coated
       with either the cognate ligand fibrinogen or monoclonal antibody
       specific for CD11b/CD18 also enhanced p24 biosynthesis. Furthermore,
       endothelial cells were found to constitutively synthesize and secrete
       soluble factors that enhanced HIV-1 synthesis. The enhancing factors, of
       estimated size 10 to 45 kD, were induced in HUVEC to high levels by
       monokines or by lipopolysaccharide, resulting in markedly enhanced HIV-1
       expression by U1. These endothelial cell-derived HIV-1-enhancing factors
       consist of, among others, interleukin-6 (IL-6), IL-1 beta, and
       granulocyte-macrophage CSF (GM-CSF). Our results suggest that activation
       of HIV biosynthesis in infected Mo via interaction with endothelium may
       impact significantly on the tissue distribution and pathogenesis of HIV
       infections.
 DE    Antibodies, Monoclonal/PHARMACOLOGY  Antigens, CD/IMMUNOLOGY  Cell Line
       Cells, Cultured  Comparative Study  Cytokines/*PHARMACOLOGY
       Endothelium, Vascular/*PHYSIOLOGY  Granulocyte-Macrophage
       Colony-Stimulating Factor/PHARMACOLOGY  Human  HIV Core Protein
       p24/BIOSYNTHESIS  HIV-1/DRUG EFFECTS/*PHYSIOLOGY
       Interleukin-6/PHARMACOLOGY  Kinetics  Lipopolysaccharides/PHARMACOLOGY
       Monocytes  Support, U.S. Gov't, P.H.S.  Time Factors  Tumor Cells,
       Cultured  Tumor Necrosis Factor/PHARMACOLOGY  Umbilical Veins  *Virus
       Replication/DRUG EFFECTS  JOURNAL ARTICLE

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