Interferon-gamma induced proliferation of human myeloid leukaemia cell lines.
Interferon-gamma (IFN-gamma) is a pleiotropic cytokine involved in the regulation of various phases of immune and inflammatory responses; it also has anti-viral and anti-proliferative activity. Using continuous human leukaemia cell lines as model systems, we found that IFN-gamma stimulated the proliferation of leukaemic myeloid cells; this effect was specifically neutralized by an anti-IFN-gamma monoclonal antibody (McAb). No proliferative response was seen in autonomously growing cell lines; however, 11/19 constitutively growth factor-dependent cell lines showed a significant response in short-term proliferation assays upon incubation with IFN-gamma. The stimulation indices ranged from 2 to 37 compared with the untreated control cells; the EC50 values for these cell lines were in the range of 0.1-0.6 ng/ml IFN-gamma. Flow cytometric analysis demonstrated heterogeneity in the expression of the IFN-gamma receptor, as it was found on 37-97% of the cells per cell line. The effects of IFN-gamma on proliferation triggered by a spectrum of 10 other cytokines were variable, and both stimulation and attenuation of the proliferative responses were seen in different cell lines. Under serum-free culture conditions, IFN-gamma acted as a survival factor suppressing apoptosis. As has been described for other functional processes triggered by IFN-gamma, the proliferation-inducing activity of IFN-gamma also led to activation of the signal transducing element STAT 1. Thus, IFN-gamma can induce myeloid leukaemia cells to proliferate and can modulate their proliferative response to other cytokines. Therefore IFN-gamma may be a pathologically relevant ligand for leukaemic cell proliferation in vivo. In physiological settings, IFN-gamma might be a bifunctional regulator of haemopoietic cell proliferation, depending on other differential co-signals from the micro-environment.
Drexler
H G
HG
DSMZ-German Collection of Microorganisms and Cell Cultures, Department of Human and Animal Cell Cultures, Braunschweig, Germany.
Zaborski
M
M
Quentmeier
H
H
D000328:Adult; D000368:Aged; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival; D004347:Drug Interactions; D005260:Female; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D007223:Infant; D007371:Interferon-gamma / Q000494:pharmacology*; D007951:Leukemia, Myeloid / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D018121:Receptors, Cytokine / Q000378:metabolism; D017471:Receptors, Interferon / Q000378:metabolism; D014407:Tumor Cells, Cultured; D000096743:Interferon gamma Receptor
D006133:Growth Substances; D007371:Interferon-gamma; D018121:Receptors, Cytokine; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor