Interleukin-4 inhibits proliferation of human leukemic megakaryoblast cell line MHH 225.
The effects of six recombinant human cytokines: erythropoietin, GM-CSF, G-CSF, interleukin-3, -4 and -6 on the proliferation and differentiation of a human multilineage myeloid leukemia cell line MHH 225, established from the bone marrow of an AML(M7) patient in our laboratory determined by changes in antigen expressions using monoclonal antibodies in APAAP technique were examined in liquid suspension culture. The MHH 225 cells have been growing exponentially without cytokines or conditioned media. About 90 per cent of MHH 225 cells are CD33+ CD34+ CD3- CD7- CD19- CD20- TdT- with 57.6 per cent, 28.3 per cent and 7.8 per cent of them being CD41+, glycophorin A+ and CD15+, respectively. After five days of treatment with erythropoietin, GM-CSF, G-CSF or IL-6 no change was observed in MHH 225 cell antigens expression. IL-3 (100 U/ml) induced a moderate increase in only CD13 and alpha naphthyl esterase positive cells from 6.5 +/- 1.9 per cent and 5.7 +/- 2.4 per cent in control cultures to 21.6 +/- 3.0 per cent and 19.1 +/- 2.8 per cent, respectively. On the other hand, 100 U/ml IL-4 significantly increased the number of CD13, CD15 and alpha naphthyl esterase positive cells to 48.9 +/- 5.0 per cent, 47.2 +/- 3.6 per cent and 46.1 +/- 3.0 per cent, p < 0.001, respectively. Also, 100 U/ml IL-4 decreased the number of CD41 positive cells from 57.6 +/- 2.8 per cent to only 25.9 +/- 3.6 per cent and did not change the number of CD33 or glycophorin A positive cells. The present results showed that out of the six myelopoietic growth factors tested, IL-4 was the only one to inhibit selectively the proliferation of CD33+ CD41+ leukemic megakaryoblast cells suggesting that IL-4 may have a lineage regulatory effect in favour of a myeloblastic CD33+ CD13+ CD15+ at the expense of a megakaryoblastic CD33+ CD41+ amplification in human leukemia cells and with apparently no effect on leukemic erythroblast cells. The MHH 225 cell line provides a useful tool and freely available model to scientists for studying signal transduction via IL-4 and for studies of 'lineage switch'.
Hassan
H T
HT
Department of Haematology and Oncology, Medizinische Hochschule Hannover, Germany.
Grell
S
S
Borrmann-Danso
U
U
Freund
M
M
D015703:Antigens, CD / Q000032:analysis; D001402:B-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D016207:Cytokines / Q000494:pharmacology*; D004921:Erythropoietin / Q000494:pharmacology; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D016130:Immunophenotyping; D007377:Interleukin-3 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology; D007951:Leukemia, Myeloid; D007962:Leukocytes / Q000276:immunology; D008533:Megakaryocytes; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D016207:Cytokines; D007377:Interleukin-3; D015850:Interleukin-6; D011994:Recombinant Proteins; D004921:Erythropoietin; D016179:Granulocyte Colony-Stimulating Factor; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor