Stromal cell lines derived from LP-BM5 murine leukemia virus-infected long-term bone marrow cultures impair hematopoiesis in vitro

Abstract

Murine acquired immunodeficiency syndrome (MAIDS) induced by defective LP-BM5 murine leukemia virus is a disease with many similarities to human AIDS. Previous studies indicated that the depressed hematopoiesis observed in LP-BM5-infected marrow cultures may be attributable to a defect of hematopoietic stroma. We report here the generation of permanent stromal cell lines from noninfected and LP-BM5-infected marrow cultures. Retrovirus infection was confirmed by polymerase chain reaction for viral genome. The ability of these cell lines to support in vitro hematopoiesis was studied. Results indicated that, when cocultured with normal or infected nonadherent mononuclear cells, noninfected cell lines efficiently supported the production of hematopoietic precursors, whereas viral-infected cell lines induced suppression of both normal and viral-infected progenitors. Expression of cytokine genes in stromal cell lines was also examined. All cell lines expressed equivalent levels of transcripts for stem cell factor and tumor necrosis factor alpha. However, infection was associated with higher levels of interleukin-4 and transforming growth factor beta 1 transcript expression. These findings suggest that infected stromal cell lines exhibit a defective hematopoietic microenvironment that produced altered cytokine expression resulting in faulty hematopoiesis. Further characterization of the defective cell lines should prove valuable for studies of the pathogenesis of murine AIDS.

Suppression of Rat Bone Marrow Cells by Friend Murine Leukemia Virus Envelope Proteins

“…Many retroviruses can cause hematopoietic abnormalities, including HIV in humans (Maciejewski et al, 1994;Re et al, 1994), SIV in monkeys (Mandell et al, 1995;Watanabe et al, 1990), FIV in cats (Linenberger and Abkowitz, 1995), and MuLV in mice (Li and Fan, 1990;Tse et al, 1994). Here we report that retroviral infection of rats also caused bone marrow alterations.…”

Impaired cytokine production by bone marrow stromal cells of immunodeficient mice

“…Tse et al (1993) demonstrated that growth of haemopoietic progenitors is impaired in long-term bone marrow cultures (LTBMC) of MAIDS mice. More recently, they demonstrated defective cytokine production in LP-BM5-infected established bone marrow stromal cell lines (Tse et al, 1994).…”

Neural Cell Adhesion Molecule Contributes to Hemopoiesis‐Supporting Capacity of Stromal Cell Lines

“…The production of cytokines was estimated using reverse transcription-polymerase chain reaction (RT-PCR) assays with previously defined primers [34][35][36][37][38]. Amplifications (30 to 35 times) were performed according to established protocols and using known controls [34][35][36][37][38].…”