Human immunodeficiency virus infection of bone marrow endothelium reduces induction of stromal hematopoietic growth factors

Ashlee Moses, S. Williams, M. L. Heneveld, J. Strussenberg, M. Rarick, M. Loveless, G. Bagby, Jay Nelson

Research output: Contribution to journalArticle

127 Citations (Scopus)

Abstract

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 bono 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)-α, transforming growth factor (TGF)-β, and Steel factor, IL- 1α-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.

Original languageEnglish (US)
Pages (from-to)919-925
Number of pages7
JournalBlood
Volume87
Issue number3
StatePublished - Feb 1 1996
Externally publishedYes

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Virus Diseases
Viruses
Endothelium
Intercellular Signaling Peptides and Proteins
Bone
Bone Marrow
HIV
Stromal Cells
Endothelial cells
Endothelial Cells
Interleukin-6
Colony-Stimulating Factors
Stem Cell Factor
Lymphoproliferative Disorders
Transforming Growth Factors
Granulocyte Colony-Stimulating Factor
Granulocyte-Macrophage Colony-Stimulating Factor
Interleukin-1
Interleukin-4
Disease Progression

ASJC Scopus subject areas

  • Hematology

Cite this

Moses, A., Williams, S., Heneveld, M. L., Strussenberg, J., Rarick, M., Loveless, M., ... Nelson, J. (1996). Human immunodeficiency virus infection of bone marrow endothelium reduces induction of stromal hematopoietic growth factors. Blood, 87(3), 919-925.

Human immunodeficiency virus infection of bone marrow endothelium reduces induction of stromal hematopoietic growth factors. / Moses, Ashlee; Williams, S.; Heneveld, M. L.; Strussenberg, J.; Rarick, M.; Loveless, M.; Bagby, G.; Nelson, Jay.

In: Blood, Vol. 87, No. 3, 01.02.1996, p. 919-925.

Research output: Contribution to journalArticle

Moses, A, Williams, S, Heneveld, ML, Strussenberg, J, Rarick, M, Loveless, M, Bagby, G & Nelson, J 1996, 'Human immunodeficiency virus infection of bone marrow endothelium reduces induction of stromal hematopoietic growth factors', Blood, vol. 87, no. 3, pp. 919-925.
Moses A, Williams S, Heneveld ML, Strussenberg J, Rarick M, Loveless M et al. Human immunodeficiency virus infection of bone marrow endothelium reduces induction of stromal hematopoietic growth factors. Blood. 1996 Feb 1;87(3):919-925.
Moses, Ashlee ; Williams, S. ; Heneveld, M. L. ; Strussenberg, J. ; Rarick, M. ; Loveless, M. ; Bagby, G. ; Nelson, Jay. / Human immunodeficiency virus infection of bone marrow endothelium reduces induction of stromal hematopoietic growth factors. In: Blood. 1996 ; Vol. 87, No. 3. pp. 919-925.
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