Abstract
In this study, we examined the potential role of the human immunodeficiency virus (HIV) tat protein in causing the hematopoietic abnormalities frequently observed in HIV-infected individuals. Recombinant tat (r-tat) protein, at concentrations up to 10 μg/mL, did not display any stimulatory or inhibitory effect on the survival/proliferate capacity of CD34+ hematopoietic progenitor cells, purified from normal bone marrow (BM). However, exposure of r-tat protein (at concentrations between 10 ng/mL and 10 μg/mL) to enriched normal BM macrophages induced the production of a factor(s) in conditioned media that inhibited the in vitro growth of CD34+ cells in liquid cultures and of immature hematopoietic progenitors (day 14 colony-forming unit-granulocyte-macrophage, burst-forming unit-erythroid, and colony-forming unit-megakaryocyte) in semisolid assays. Pre-exposure of r-tat protein with a monoclonal neutralizing anti-tat antibody completely abrogated the inhibitory activity present in BM macrophage culture supernatants. The main factor responsible for this suppressive activity was transforming growth factor-β1 (TGF-β1), as shown by the ability of a polyclonal anti-TGF-β1 neutralizing antibody to almost completely reverse the suppressive effect of BM macrophage supernatants on CD34+cells. TGF-β1 bioassays showed that exposure of r-tat protein to BM macrophages significantly increased the levels of both active and latent forms of TGF-β1. These results indicate that the production of TGF-β1, one of the most potent negative regulator of hematopoiesis, is increased by HIV tat protein and that such increase could contribute to the derangement of the hematopoietic system in HIV-infected individuals.
| Original language | English |
|---|---|
| Pages (from-to) | 3036-3043 |
| Number of pages | 8 |
| Journal | Blood |
| Volume | 80 |
| Issue number | 12 |
| Publication status | Published - Dec 15 1992 |
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ASJC Scopus subject areas
- Hematology
Cite this
Tat protein stimulates production of transforming growth factor-β1 by marrow macrophages : A potential mechanism for human immunodeficiency virus-1-induced hematopoietic suppression. / Zauli, Giorgio; Davis, Brian R.; Re, Maria Carla; Visani, Giuseppe; Furlini, Giuliano; La Placa, Michele.
In: Blood, Vol. 80, No. 12, 15.12.1992, p. 3036-3043.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Tat protein stimulates production of transforming growth factor-β1 by marrow macrophages
T2 - A potential mechanism for human immunodeficiency virus-1-induced hematopoietic suppression
AU - Zauli, Giorgio
AU - Davis, Brian R.
AU - Re, Maria Carla
AU - Visani, Giuseppe
AU - Furlini, Giuliano
AU - La Placa, Michele
PY - 1992/12/15
Y1 - 1992/12/15
N2 - In this study, we examined the potential role of the human immunodeficiency virus (HIV) tat protein in causing the hematopoietic abnormalities frequently observed in HIV-infected individuals. Recombinant tat (r-tat) protein, at concentrations up to 10 μg/mL, did not display any stimulatory or inhibitory effect on the survival/proliferate capacity of CD34+ hematopoietic progenitor cells, purified from normal bone marrow (BM). However, exposure of r-tat protein (at concentrations between 10 ng/mL and 10 μg/mL) to enriched normal BM macrophages induced the production of a factor(s) in conditioned media that inhibited the in vitro growth of CD34+ cells in liquid cultures and of immature hematopoietic progenitors (day 14 colony-forming unit-granulocyte-macrophage, burst-forming unit-erythroid, and colony-forming unit-megakaryocyte) in semisolid assays. Pre-exposure of r-tat protein with a monoclonal neutralizing anti-tat antibody completely abrogated the inhibitory activity present in BM macrophage culture supernatants. The main factor responsible for this suppressive activity was transforming growth factor-β1 (TGF-β1), as shown by the ability of a polyclonal anti-TGF-β1 neutralizing antibody to almost completely reverse the suppressive effect of BM macrophage supernatants on CD34+cells. TGF-β1 bioassays showed that exposure of r-tat protein to BM macrophages significantly increased the levels of both active and latent forms of TGF-β1. These results indicate that the production of TGF-β1, one of the most potent negative regulator of hematopoiesis, is increased by HIV tat protein and that such increase could contribute to the derangement of the hematopoietic system in HIV-infected individuals.
AB - In this study, we examined the potential role of the human immunodeficiency virus (HIV) tat protein in causing the hematopoietic abnormalities frequently observed in HIV-infected individuals. Recombinant tat (r-tat) protein, at concentrations up to 10 μg/mL, did not display any stimulatory or inhibitory effect on the survival/proliferate capacity of CD34+ hematopoietic progenitor cells, purified from normal bone marrow (BM). However, exposure of r-tat protein (at concentrations between 10 ng/mL and 10 μg/mL) to enriched normal BM macrophages induced the production of a factor(s) in conditioned media that inhibited the in vitro growth of CD34+ cells in liquid cultures and of immature hematopoietic progenitors (day 14 colony-forming unit-granulocyte-macrophage, burst-forming unit-erythroid, and colony-forming unit-megakaryocyte) in semisolid assays. Pre-exposure of r-tat protein with a monoclonal neutralizing anti-tat antibody completely abrogated the inhibitory activity present in BM macrophage culture supernatants. The main factor responsible for this suppressive activity was transforming growth factor-β1 (TGF-β1), as shown by the ability of a polyclonal anti-TGF-β1 neutralizing antibody to almost completely reverse the suppressive effect of BM macrophage supernatants on CD34+cells. TGF-β1 bioassays showed that exposure of r-tat protein to BM macrophages significantly increased the levels of both active and latent forms of TGF-β1. These results indicate that the production of TGF-β1, one of the most potent negative regulator of hematopoiesis, is increased by HIV tat protein and that such increase could contribute to the derangement of the hematopoietic system in HIV-infected individuals.
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UR - http://www.scopus.com/inward/citedby.url?scp=0027096251&partnerID=8YFLogxK
M3 - Article
VL - 80
SP - 3036
EP - 3043
JO - Blood
JF - Blood
SN - 0006-4971
IS - 12
ER -