当前位置： SCI文献检索 > VIRUS RESEARCH期刊下所有文献 > Reconstitution of erythroid, megakaryocyte and myeloid hematopoietic support function with neutralizing antibodies against IL-4 and TGFbeta1 in long-term bone marrow cultures infected with LP-BM5 murine leukemia virus.

Reconstitution of erythroid, megakaryocyte and myeloid hematopoietic support function with neutralizing antibodies against IL-4 and TGFbeta1 in long-term bone marrow cultures infected with LP-BM5 murine leukemia virus.

Abstract：

:Murine acquired immunodeficiency syndrome (MAIDS) induced by a defective LP-BM5 murine leukemia virus (MuLV) produces hematopoietic cytopenias similar to HIV in patients with AIDS. The pathogenesis of MAIDS induced cytopenias remains obscure; however, direct retroviral infection of bone marrow stroma has been implicated to play a role. To evaluate the consequential effect of viral infection, primary stromal cell cultures were transiently incubated in vitro with LP-BM5 MuLV viral supernatant. Reverse transcription polymerase chain reaction (RT-PCR) and Southern blot hybridization revealed that defective LP-BM5 MuLV infection resulted in elevated levels of IL-4 and TGFbeta1 transcript expression in infected stromal cells. The increased expression of both IL-4 and TGFbeta1 transcripts was associated with enhanced production of corresponding proteins as determined by quantitative western blot analyses. Hematopoietic reconstitution assays revealed that the hematopoietic support function of stromal cells was significantly reduced following transient exposure to LP-BM5 MuLV. The production of nonadherent mononuclear cells and the growth of myeloid, megakaryocyte and erythroid lineages were all suppressed in infected cultures. Culture supernatant conditioned by infected stromal cells demonstrated growth-inhibitory activity for hematopoietic progenitor colony formation. This growth-inhibitory activity could be significantly abolished by addition of anti-IL-4 and/or anti-TGFbeta1 neutralizing antibodies to the culture supernatant or directly to the stromal cell cultures. This study demonstrates LP-BM5 MuLV increases two known cytokines to suppress hematopoiesis implicating viral infection can directly suppress hematopoiesis mediated by inhibitors released from marrow stroma.

journal_name

Virus Res

journal_title

Virus research

authors

Tse KF,Inayat MS,Morrow JK,Hughes NK,Oakley OR,Gallicchio VS

doi

10.1016/j.virusres.2005.03.027

subject

Has Abstract

pub_date

2005-10-01 00:00:00

pages

1-15

issue

1

eissn

0168-1702

issn

1872-7492

pii

S0168-1702(05)00095-X

journal_volume

113

pub_type

杂志文章

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