Effect of recombinant murine tumor necrosis factor on the generation of natural killer cells in bone marrow cultures.
We investigated the possible role of tumor necrosis factor-alpha (TNF-alpha) in the interleukin-2 (IL-2)-dependent generation of natural killer (NK) cells from bone marrow precursors. TNF-alpha synergistically augmented both cytotoxic activity against NK-sensitive targets and cell number at the end of the 7-day incubation period. After this time, NK activity was not induced by TNF-alpha in the absence of IL-2. The cytotoxic cells generated by IL-2 + TNF-alpha had the phenotype of mature NK cells, including expression of NK-1.1, asialo-GM1, Ly-5, LFA-1 and Thy-1. TNF-alpha was also able to up-regulate the mRNA expression for the IL-2 receptor alpha-chain (P55) as well as the mRNA expression of c-myc protooncogene. Blocking studies with monoclonal antibodies against the alpha-chain P55 of the IL-2 receptor confirmed the functional role ascribed to IL-2 in the in vitro generation of NK cells from bone marrow cultures. Additional proliferation studies demonstrated that the up-regulation of c-myc protooncogene was associated with an increased uptake of thymidine. These data indicate that the TNF-alpha-induced increase of IL-2-dependent NK cell generation from bone marrow precursors was associated with an augmented proliferation and an up-regulation of mRNA expression for IL-2 receptor and c-myc protooncogene.
Ayroldi
E
E
Institute of Pharmacology, University of Perugia, Italy.
Sorci
G
G
Cannarile
L
L
Riccardi
C
C
D000818:Animals; D000954:Antigens, Surface; D002478:Cells, Cultured; D016259:Genes, myc; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology*; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D000954:Antigens, Surface; D007376:Interleukin-2; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D014409:Tumor Necrosis Factor-alpha