Document 0276
 DOCN  M9650276
 TI    Human immunodeficiency virus infection of bone marrow endothelium
       reduces induction of stromal hematopoietic growth factors.
 DT    9605
 AU    Moses AV; Williams S; Heneveld ML; Strussenberg J; Rarick M; Loveless M;
       Bagby G; Nelson JA; Department of Molecular Microbiology, Oregon Health
       Sciences; University, Portland, USA.
 SO    Blood. 1996 Feb 1;87(3):919-25. Unique Identifier : AIDSLINE
       MED/96151972
 AB    The majority of human immunodeficiency virus (HIV)-seropositive patients
       develop bone marrow abnormalities associated with hematopoietic
       malfunction during the progression of disease. One important
       manifestation of HIV-associated hematopoietic dysfunction is that after
       myelosuppression, bone marrow recovery, a process known to be mediated
       in part by the production of stromal cell-derived hematopoietic growth
       factors, is impaired. We sought to test the hypothesis that bone marrow
       stromal cells are infected by HIV-1 in vivo and that production of
       certain stromal cell-derived hematopoietic growth factors is deficient
       as a consequence. In this report, we demonstrate that bone marrow
       microvascular endothelial cells (MVEC), a key element of the stroma, are
       the predominant cells infected by HIV (5% to 20%) in bone marrow stromal
       cultures obtained from 11 consecutive HIV-seropositive patients.
       Although HIV-infected stromal cultures enriched for MVEC constitutively
       express normal levels of interleukin (IL)-4, IL-6, granulocyte
       (G)-colony-stimulating factor (CSF), granulocyte-macrophage (GM)-CSF,
       tumor necrosis factor (TNF)-alpha, transforming growth factor
       (TGF)-beta, and Steel factor, IL-1 alpha-induced release of IL-6 and
       G-CSF is significantly reduced in these cultures. These observations
       suggest that HIV infection of bone marrow MVEC reduces the capacity of
       hematopoietic stroma to respond to regulatory signals that normally
       augment blood cell production during periods of increased demand.
 DE    von Willebrand Factor/ANALYSIS  Adult  Antigens, CD34/ANALYSIS
       Biological Markers  Bone Marrow/BLOOD SUPPLY/METABOLISM/*VIROLOGY
       Cells, Cultured  Cytokines/BIOSYNTHESIS  Endothelium,
       Vascular/METABOLISM/VIROLOGY  Female  Hematopoiesis  Hematopoietic Cell
       Growth Factors/*BIOSYNTHESIS  Human  HIV
       Infections/BLOOD/*PHYSIOPATHOLOGY  HIV-1/*PHYSIOLOGY  Male  Middle Age
       Support, Non-U.S. Gov't  Support, U.S. Gov't, P.H.S.  JOURNAL ARTICLE

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