Important note: Information in this article was accurate in 1995. The state of the art may have changed since the publication date.
Suppression of hematopoietic support function is associated with overexpression of IL-4 and TGF beta 1 in LP-BM5 MuLV infected stromal cell lines (Meeting abstract).
Proc Annu Meet Am Assoc Cancer Res; 36:A1184 1995. Unique Identifier : AIDSLINE ICDB/95608961 Tse KF; Morrow JK; Hughes NK; Gallicchio VS; Univ. of Kentucky Medical Center, Lexington, KY 40536
Abstract:
Murine acquired immunodeficiency syndrome (MAIDS) induced by defective LPBM5 murine leukemia virus is a disease which shares many similarities to human AIDS. The pathogenesis of MAIDS is currently not understood, but may involve the consequential effect of stroma infection in the bone marrow resulting in a defective hematopoietic microenvironment. To evaluate the effect of infection on the hematopoietic stroma, we generated permanent stromal cell lines from LP-BM5 infected and noninfected primary marrow cultures. Retroviral infection in infected cell lines was confirmed by the expression of defective viral gag p12 sequence via RT-PCR and the production of viral particles. The ability of these cell lines to support in vitro hematopoiesis was studied. Results indicated that when cocultured with either noninfected or infected nonadherent mononuclear cells, noninfected control cell lines efficiently supported the production of hematopoietic precursors, whereas virus-infected cell lines induced suppression of both noninfected and virus-infected progenitors. Expression of several cytokine genes in stromal cell lines was also determined by RT-PCR. All cell lines expressed equivalent levels of transcripts for stem cell factor, IL-3, IL-7 and TNF alpha. However, infection was associated with higher levels of IL-4 and TGF beta 1 mRNA expression. These findings suggest that LP-BM5 infection of stromal cells leads to defective hematopoietic support function and altered cytokine expression. Further characterization of the defective cell lines should prove valuable for studies of the pathogenesis of murine AIDS.
Keywords: Animal Bone Marrow/*PHYSIOPATHOLOGY Cell Line Interleukin-4/*GENETICS Leukemia Viruses, Murine/ISOLATION & PURIF/*PHYSIOLOGY Mice Polymerase Chain Reaction RNA, Messenger/GENETICS/METABOLISM Transforming Growth Factor beta/*GENETICS ABSTRACT 950930
M9591327
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