Production of hemo- and immunoregulatory cytokines by erythroblast antigen super(+ )and glycophorin A super(+ )cells from human bone marrow

Background: Erythroid nuclear cells (ENC) of the bone marrow (BM) have not previously been considered as important producers of wide spectrum of haemo- and immunoregulatory cytokines. The aim of the current work was to confirm the production of the main hemo- and immunoregulatory cytokines in human ENC from BM. Results: We used native human BM ENC in our experiments. We for the first time have shown, that the unstimulated erythroblasts (Gl A super(+ )or AG-EB super(+)) produced a wide spectrum of immunoregulatory cytokines. Human BM ENC produce cytokines such as interleukn (IL)-1b, IL-2, IL-4, IL-6, interferon (IFN)-, transforming growth factor (TGF)-b1, tumor necrosis factor (TNF)-a and IL-10. They can be sub-divided into glycophorin A positive (Gl A super(+)) and erythroblast antigen positive (AG-EB super(+)) cells. To study potential differences in cytokine expression between these subsets, ENC were isolated and purified using specific antibodies to Gl A and AG-EB and the separated cells were cultivated for 24 hours. The cytokine contents of the supernatant were measured by electrochemiluminescence immunoassay. Quantitative differences in TGF-b1 and TNF-a production were found between Gl A super(+ )and AG-EB super(+ )BM ENC. Furthermore, in vitro addition of erythropoietin (EPO) reduced IFN- and IL-2 production specifically by the AG-EB super(+ )ENC. Thus, Gl A super(+ )and AG-EB super(+ )ENC produce IL-1b, IL-2, IL-4, IL-6, IFN-, TGF-b1 and TNF-a. Gl A super(+ )ENC also produce IL-10. Conclusions: Cytokine production by erythroid nuclear cells suggests that these cells might be involved in regulating the proliferation and differentiation of hematopoietic and immunocompetent cells in human BM.