Production of hemo- and immunoregulatory cytokines by erythroblast antigen+ and glycophorin A+ 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+ or AG-EB+) produced a wide spectrum of immunoregulatory cytokines. Human BM ENC produce cytokines such as interleukin (IL)-1beta, IL-2, IL-4, IL-6, interferon (IFN)-gamma, transforming growth factor (TGF)-beta1, tumor necrosis factor (TNF)-alpha and IL-10. They can be sub-divided into glycophorin A positive (Gl A+) and erythroblast antigen positive (AG-EB+) 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-beta1 and TNF-alpha production were found between Gl A+ and AG-EB+ BM ENC. Furthermore, in vitro addition of erythropoietin (EPO) reduced IFN-gamma and IL-2 production specifically by the AG-EB+ ENC. Thus, Gl A+ and AG-EB+ ENC produce IL-1beta, IL-2, IL-4, IL-6, IFN-gamma, TGF-beta1 and TNF-alpha. Gl A+ 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.
Sennikov
Sergey V
SV
Laboratory of the Regulation of Immunopoiesis, Institute of Clinical Immunology SB RAMS, Yadrintsevskaya 14, Novosibirsk, 630099, Russia. ici@online.nsk.su
Injelevskaya
Tatyana V
TV
Krysov
Sergey V
SV
Silkov
Alexandr N
AN
Kovinev
Igor B
IB
Dyachkova
Natalya J
NJ
Zenkov
Anton N
AN
Loseva
Mary I
MI
Kozlov
Vladimir A
VA
D000941:Antigens / Q000502:physiology*; D001402:B-Lymphocytes / Q000502:physiology; D001854:Bone Marrow Cells / Q000378:metabolism*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis* / Q000502:physiology; D004900:Erythroblasts / Q000276:immunology*; D006021:Glycophorins / Q000502:physiology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000502:physiology; D007375:Interleukin-1 / Q000096:biosynthesis / Q000502:physiology; D016753:Interleukin-10 / Q000096:biosynthesis / Q000502:physiology; D007376:Interleukin-2 / Q000096:biosynthesis / Q000502:physiology; D015847:Interleukin-4 / Q000096:biosynthesis / Q000502:physiology; D015850:Interleukin-6 / Q000096:biosynthesis / Q000502:physiology; D013601:T-Lymphocytes / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000502:physiology; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000941:Antigens; D016207:Cytokines; D006021:Glycophorins; D007375:Interleukin-1; D007376:Interleukin-2; D015850:Interleukin-6; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma