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Human immunodeficiency virus infection of bone marrow endothelium reduces
induction of stromal hematopoietic growth factors [see comments]
AV Moses, S Williams, ML Heneveld, J Strussenberg, M Rarick, M Loveless, G Bagby and JA Nelson
Department of Molecular Microbiology, Oregon Health Sciences University,
Portland, USA.
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.
Volume 87,
Issue 3,
pp. 919-925,
02/01/1996
Copyright © 1996 by The American Society of Hematology
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