Impaired in vitro growth of purified (CD34+) hematopoietic progenitors in human immunodeficiency virus-1 seropositive thrombocytopenic individuals.
In this report the role played by human immunodeficiency virus type-1 (HIV-1) in the pathogenesis of HIV-1-related thrombocytopenia was investigated. CD34+ hematopoietic stem/progenitor cells were purified from the bone marrow (BM) of HIV-1(+) thrombocytopenic patients, HIV-1(+) nonthrombocytopenic individuals, HIV-1(-) patients with immune thrombocytopenic purpura, and HIV-1(-) normal donors. CD34+ cells from HIV-1(+) thrombocytopenic individuals alone showed a reduced capacity to give rise to megakaryocytic colonies (CFU-Meg) and also a progressive and significant decline in cell number when placed in liquid culture containing recombinant human interleukin-3 (rIL-3). This decline involved not only megakaryocyte but also erythroid and granulocyte/macrophage progenitors. The defects in megakaryocyte colony formation and CD34+ cell growth did not result from a productive HIV-1 infection of CD34+ cells. Moreover, HIV-1 DNA was absent from CD34+ cells in 10 of 12 thrombocytopenic patients examined. On the other hand, the decreased survival/proliferation of CD34+ cells in liquid culture, within the HIV-1(+) thrombocytopenic patients, was correlated with the presence of HIV-1 p24 antigen in BM plasma. These results demonstrate an impairment of CD34+ cells in HIV-1(+) individuals presenting thrombocytopenia as the only hematologic manifestation. Furthermore, these findings suggest that increased viral replication in the BM microenvironment may cause this impairment and possibly contributes to HIV-induced thrombocytopenia.
Zauli
G
G
Institute of Microbiology, University of Bologna, Italy.
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M C
MC
Davis
B
B
Sen
L
L
Visani
G
G
Gugliotta
L
L
Furlini
G
G
La Placa
M
M
D000163:Acquired Immunodeficiency Syndrome / Q000097:blood / Q000473:pathology*; D000328:Adult; D015703:Antigens, CD / Q000032:analysis*; D018952:Antigens, CD34; D001853:Bone Marrow / Q000473:pathology*; D002455:Cell Division; D002478:Cells, Cultured; D004279:DNA, Viral / Q000032:analysis / Q000235:genetics; D005260:Female; D006679:HIV Seropositivity; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification; D006412:Hematopoietic Stem Cells / Q000473:pathology*; D006801:Humans; D007700:Kinetics; D008297:Male; D011533:Proviruses / Q000235:genetics / Q000302:isolation & purification; D013921:Thrombocytopenia / Q000097:blood / Q000473:pathology*
D015703:Antigens, CD; D018952:Antigens, CD34; D004279:DNA, Viral