Tat protein stimulates production of transforming growth factor-β1 by marrow macrophages: A potential mechanism for human immunodeficiency virus-1-induced hematopoietic suppression

Giorgio Zauli, Brian R. Davis, Maria Carla Re, Giuseppe Visani, Giuliano Furlini, Michele La Placa

Research output: Contribution to journalArticlepeer-review

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 languageEnglish
Pages (from-to)3036-3043
Number of pages8
JournalBlood
Volume80
Issue number12
Publication statusPublished - Dec 15 1992

ASJC Scopus subject areas

  • Hematology

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