Suppression of hematopoietic support function is associated with overexpression of interleukin-4 and transforming growth factor-beta 1 in LP-BM5 murine-leukemia-virus-infected stromal cell lines.
Murine acquired immunodeficiency syndrome (MAIDS) induced by defective LP-BM5 murine leukemia virus (MuLV) is a disease with many similarities to human AIDS. Our previous studies demonstrated that the depressed hematopoiesis observed in LP-BM5-infected marrow cultures could be attributed to a defective hematopoietic stroma. We report now the generation of permanent stroma cell lines from noninfected and LP-BM5-infected marrow cultures. Retrovirus infection was confirmed by the polymerase chain reaction for detecting viral genome expression of the p12 envelope glycoprotein. The ability of these cell lines to support in vitro hematopoiesis was evaluated. The results demonstrated that when cocultured with normal or infected nonadherent mononuclear cells, noninfected cell lines efficiently supported the production of hematopoietic progenitors, whereas in virus-infected progenitors was suppressed. Expression of cytokine genes in stromal cell lines was also examined. All cell lines expressed equivalent levels of transcripts for interleukin (IL)-1 beta, IL-2, IL-3, IL-6, IL-7, IL-10, interferon, tumor necrosis factor-alpha and stem cell factor. However, infection was associated with higher expression of IL-4 and transforming growth factor-beta 1. These findings demonstrate that infected stomal cell lines generate a defective hematopoietic microenvironment to produce altered cytokine expression and faulty hematopoiesis. Further characterization of these defective cell lines should assist elucidation of the mechanism(s) whereby retroviruses alter hematopoiesis ultimately leading to the generation of immunodeficiency.
Gallicchio
V S
VS
Department of Internal Medicine, Lucille P. Markey Cancer Center, Chandler Medical Center, University of Kentucky, Lexington 0536-0084 (USA).
Tse
K F
KF
Morrow
J
J
Hughes
N K
NK
D000818:Animals; D001853:Bone Marrow / Q000502:physiology / Q000821:virology; D001854:Bone Marrow Cells; D002460:Cell Line; D016207:Cytokines / Q000235:genetics; D004591:Electrophoresis, Polyacrylamide Gel; D005786:Gene Expression Regulation; D015683:Gene Products, gag / Q000235:genetics; D006410:Hematopoiesis / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D015847:Interleukin-4 / Q000096:biosynthesis*; D009052:Leukemia Virus, Murine / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016183:Murine Acquired Immunodeficiency Syndrome / Q000473:pathology / Q000821:virology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D017154:Stromal Cells / Q000502:physiology / Q000821:virology; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*
D016207:Cytokines; D015683:Gene Products, gag; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D015847:Interleukin-4