       Document 0679
 DOCN  M9640679
 TI    Inhibition of purified CD34+ hematopoietic progenitor cells by human
       immunodeficiency virus 1 or gp120 mediated by endogenous transforming
       growth factor beta 1.
 DT    9604
 AU    Zauli G; Vitale M; Gibellini D; Capitani S; Institute of Human Anatomy,
       University of Ferrara, Italy.
 SO    J Exp Med. 1996 Jan 1;183(1):99-108. Unique Identifier : AIDSLINE
       MED/96136752
 AB    Human CD34+ hematopoietic progenitor cells, stringently purified from
       the peripheral blood of 20 normal donors, showed an impaired survival
       and clonogenic capacity after exposure to either heat-inactivated human
       immunodeficiency virus (HIV) 1 (strain IIIB) or cross-linked envelope
       gp120. Cell cycle analysis, performed at different times in serum-free
       liquid culture, showed an accumulation in G0/G1 in HIV-1- or
       gp120-treated cells and a progressive increase of cells with subdiploid
       DNA content, characteristic of apoptosis. In blocking experiments with
       anti-transforming growth factor (TGF) beta 1 neutralizing serum or
       TGF-beta 1 oligonucleotides, we demonstrated that the HIV-1- or
       gp120-mediated suppression of CD34+ cell growth was almost entirely due
       to an upregulation of endogenous TGF-beta 1 produced by purified
       hematopoietic progenitors. Moreover, by using a sensitive assay on the
       CCL64 cell line, increased levels of bioactive TGF-beta 1 were recovered
       in the culture supernatant of HIV-1/gp120-treated CD34+ cells.
       Anti-TGF-beta 1 neutralizing serum or TGF-beta 1 oligonucleotides were
       also effective in inducing a significant increase of the plating
       efficiency of CD34+ cells, purified from the peripheral blood of three
       HIV-1-seropositive individuals, suggesting that a similar mechanism may
       be also operative in vivo. The relevance of these findings to a better
       understanding of the pathogenesis of HIV-1-related cytopenias is
       discussed.
 DE    *Antigens, CD34  Base Sequence  Cell Cycle  Cells, Cultured  Culture
       Media, Serum-Free  Female  Hematopoietic Stem Cells/*PHYSIOLOGY/VIROLOGY
       Human  HIV Envelope Protein gp120/GENETICS/*METABOLISM  HIV
       Seropositivity/PATHOLOGY  HIV-1/GENETICS/*METABOLISM
       Leukopenia/ETIOLOGY  Male  Molecular Sequence Data  Oligonucleotides,
       Antisense  Recombinant Proteins/METABOLISM  RNA, Messenger/ANALYSIS
       Support, Non-U.S. Gov't  Transforming Growth Factor
       beta/*BIOSYNTHESIS/GENETICS/IMMUNOLOGY  Up-Regulation (Physiology)
       JOURNAL ARTICLE

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

