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M9650276.TXT
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1996-03-09
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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).