Document 1151
 DOCN  M9591151
 TI    Negative regulators may mediate some of the inhibitory effects of HIV-1
       infected stromal cell layers on erythropoiesis and myelopoiesis in human
       bone marrow long term cultures.
 DT    9509
 AU    Schwartz GN; Kessler SW; Szabo JM; Burrell LM; Francis ML;
       Transplantation Therapy Section, National Cancer Institute,; National
       Institutes of Health, Bethesda, MD 20892, USA.
 SO    J Leukoc Biol. 1995 Jun;57(6):948-55. Unique Identifier : AIDSLINE
       MED/95310805
 AB    This report presents results concerning the potential role of negative
       regulators in hematopoietic suppression observed in human
       immunodeficiency virus (HIV)-infected long-term cultures (LTC) of human
       bone marrow cells. Confluent stromal cell layers established from human
       bone marrow cells were exposed to HIV-1ADA, a monocytotropic strain of
       HIV-1. A progressive increase in the concentration of HIV-1 p24 antigen
       in cultures exposed to HIV-1ADA demonstrated that there was a productive
       infection. Cells from both noninfected and HIV-infected stromal cell
       layers produced factors that stimulated the proliferation of
       colony-forming units for granulocytes and macrophages (CFU-GM) from
       non-infected CD34+ cells. In contrast, when noninfected CD34+ cells were
       directly cocultured on intact stromal cell layers fewer CFU-GM and
       burst-forming units for erythroid cells (BFU-E) were detected in
       HIV-infected LTC than in noninfected LTC. One week after the addition of
       CD34+ cells, the number of CFU-GM in HIV-infected LTC in six of nine
       experiments was reduced compared to noninfected control LTC. In those
       six experiments, the number of CFU-GM was only 53 +/- 5% (SEM) of the
       number in noninfected LTC. The number of BFU-E in HIV-1-infected LTC was
       only 46 +/- 5% of the number in noninfected LTC (n = 5). There were
       fewer BFU-E in HIV-1-infected LTC, whether or not there was a reduced
       number of CFU-GM. Neutralizing antibody to tumor necrosis factor alpha
       (TNF-alpha) had no effect on the number of BFU-E in HIV-infected LTC.
       The number of BFU-E, however, was 2.1 +/- 0.2-fold greater (n = 3) in
       HIV-infected LTC incubated with neutralizing antibody to
       interferon-alpha. In HIV-infected LTC with decreased numbers of CFU-GM,
       the number of CFU-GM was approximately 2-fold greater after incubation
       of HIV-infected LTC with anti-interleukin-4 (IL-4). The effect of
       anti-TNF-alpha was variable, and anti-transforming growth factor-beta
       had no effect on the number of CFU-GM in HIV-infected LTC. After 2
       weeks, the number of CFU-GM in HIV-infected LTC incubated with anti-IL-4
       and anti-TNF-alpha was 2- to 4-fold greater than in untreated
       HIV-infected LTC. Antibody treatment did not promote an increase in the
       number of CFU-GM in noninfected LTC or in LTC in which CFU-GM numbers
       were not reduced after HIV infection.(ABSTRACT TRUNCATED AT 400 WORDS)
 DE    Antigens, CD/ANALYSIS  Bone Marrow/*CYTOLOGY/VIROLOGY  Cells, Cultured
       Cytokines/*PHYSIOLOGY  *Erythropoiesis  *Hematopoiesis  Human
       HIV-1/*PHYSIOLOGY  Interferon-alpha/PHYSIOLOGY  Interleukin-4/PHYSIOLOGY
       Stromal Cells/VIROLOGY  Support, U.S. Gov't, Non-P.H.S.  Transforming
       Growth Factor beta/PHYSIOLOGY  Tumor Necrosis Factor/PHYSIOLOGY  JOURNAL
       ARTICLE

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