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Stromal cell lines derived from LP-BM5 murine leukemia virus-infected
long-term bone marrow cultures impair hematopoiesis in vitro
KF Tse, JK Morrow, NK Hughes and VS Gallicchio
Department of Internal Medicine, University of Kentucky Medical Center,
Lexington.
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.
Volume 84,
Issue 5,
pp. 1508-1518,
09/01/1994
Copyright © 1994 by The American Society of Hematology
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