Characterization of a monocyte differentiation factor distinct from gamma-interferon, tumor necrosis factor, or G,M-colony-stimulating factor that regulates the growth and functional capabilities of the U937 monocytic cell line.
We have analyzed the characteristics and cellular sources of the T cell-derived lymphokines that affect the proliferation and the oxidative metabolic capabilities of the U937 monocytic cell line. Although gamma-interferon (gIFN) and tumor necrosis factor-alpha (TNFa) can, in high doses, inhibit the proliferation of U937 cells, the predominant antiproliferative factor produced by activated CD4+ and CD8+ T cells has a MW = 45-55 Kd, is resistant to heat treatment, and is distinct and independent from gIFN, TNFa, and GM-CSF. The inhibitory effect of this lymphokine on U937 cell growth requires an 18-24-hr induction period; thereafter, this growth arrest persists for up to 5 d, even in the absence of the factor. The lymphokine responsible for inducing oxidative metabolic capabilities in U937 cells is also a non-gIFN, heat-resistant, 45-55-Kd factor secreted by CD4+ and CD8+ cells, and we postulate that this differentiation factor is identical to the factor responsible for inhibiting U937 growth. These data demonstrate the prominent role of T cell-derived factors distinct from gIFN, TNFa, or GM-CSF in regulating the growth and functional capabilities of monocyte-lineage cells. Furthermore, the data suggest it may be appropriate to distinguish monocyte activation, in which cells at a given maturational stage develop a heightened ability to perform a particular function, from changes in the functional repertoire of cells acquired as a consequence of lymphokine-induced differentiation.
D002460:Cell Line; D003115:Colony-Stimulating Factors / Q000502:physiology*; D003470:Culture Media; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006131:Growth Inhibitors / Q000502:physiology*; D006133:Growth Substances / Q000502:physiology*; D006801:Humans; D007371:Interferon-gamma / Q000502:physiology*; D007700:Kinetics; D008222:Lymphokines / Q000502:physiology*; D008970:Molecular Weight; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D010101:Oxygen Consumption / Q000187:drug effects; D010641:Phenotype; D013491:Suppressor Factors, Immunologic / Q000502:physiology; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D003115:Colony-Stimulating Factors; D003470:Culture Media; D006131:Growth Inhibitors; D006133:Growth Substances; D008222:Lymphokines; D013491:Suppressor Factors, Immunologic; D014409:Tumor Necrosis Factor-alpha; C050979:monocyte-macrophage differentiation factor; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor