Cytokine-Synthesizing Activity of Erythroid Cells

The presence of mRNA of cytokines IL-1alpha, IL-1beta, IL-4, IL-6, IFN-gamma, TGF-beta, GM-CSF and the absence of mRNA of IL-2, IL-3 and IL-5 were identified in erythroid cells isolated from spleen of mice subjected to erythropoiesis-stimulating actions (treated with phenylhydrazine, acute hypoxia) and from spleen of newborn mice. Gene expression of cytokines in erythroid cells therewith differed both qualitatively and quantitatively depending on erythropoiesis-stimulating action. Erythroid cells of newborn mice contained mRNA of GM-CSF, but did not contain mRNA of IFN-gamma, whereas erythroid cells of mice under acute hypoxia or treated with phenylhydrazine had mRNA of IFN-gamma, but no mRNA of GM-CSF. After cell cultivation with erythropoietin, qualitative and quantitative changes in gene expression of cytokines were observed including the appearance of mRNA of IL-2, IL-3 but not of IL-5. The fact of gene expression of cytokines was confirmed on cells from single erythroid colonies. The level of mRNA expression of cytokines in erythroid cells was comparable with, and for a number of cytokines even higher than in splenocytes of mice immunized with T-dependent antigen. Moreover, it was demonstrated that erythroid cells are capable of translating proteins themselves. The production of GM-CSF and IFN-gamma by erythroid cells extracted from spleen of newborn mice, as well as from mice after erythropoiesis-stimulating actions (treatment with phenylhydrazine, acute hypoxia, acute blood loss) was detected. The level of IFN-gamma production was comparable with the level of production of this cytokine by mitogen-stimulated splenocytes. Thus, erythroid cells, as well as the cells of practically all hemopoietic lineages are capable to express and produce a number of hemo- and immunoregulatory cytokines by means of which they can participate in the regulation of hemo- and immunopoiesis, as well as exert a self-regulatory lineage restricted effect on cell proliferation and differentiation.