Thrombopoietin-independent effect of interferon-gamma on the proliferation of human megakaryocyte progenitors.
Flow cytometric study revealed that almost all CD34+ cells in human umbilical cord blood expressed interferon-gamma receptor (IFN-gammaR). To clarify the precise functional roles of IFN-gammaR in human CD34+ cells, we examined the effect of IFN-gamma alone and in combination with various cytokines on the growth of haemopoietic progenitor cells in CD34+ cells using a serum-free clonal culture. Surprisingly, IFN-gamma alone supported only megakaryocyte (MK) colonies in a dose-dependent manner with a plateau level at 1000 U/ml of IFN-gamma. IFN-gamma at 1000 U/ml induced 10 +/- 1.2 MK colonies from 1 x 10(3) CD34+ cells, whereas thrombopoietin (TPO), interleukin (IL)-3, stem cell factor (SCF) or IL-6 alone induced 22 +/- 4.0, 22 +/- 4.2, 4 +/- 0.6 and 0 MK colonies, respectively. The addition of anti-IFN-gamma monoclonal antibody (mAb) to the IFN-gamma culture completely abrogated MK colony formation, whereas the mAb had no effect on TPO-dependent production of MK colonies. In contrast, although anti-TPO polyclonal Ab almost completely blocked TPO-dependent MK colony formation, it failed to inhibit the generation of MK colonies induced by IFN-gamma, suggesting that the observed effect of IFN-gamma on the proliferation of human MK progenitor cells is independent of TPO. The addition of IFN-gamma to culture with TPO or SCF significantly augmented the development of MK colonies, whereas it did not affect IL-3-dependent MK colony formation. Additionally, IFN-gamma induced the increase of DNA content of cultured glycoprotein IIb/IIIa-positive megakaryocytes. These results suggest that IFN-gamma may have regulatory roles in human megakaryocytopoiesis.
Muraoka
K
K
Department of Clinical Oncology, Institute of Medical Science, University of Tokyo, Japan.
Tsuji
K
K
Yoshida
M
M
Ebihara
Y
Y
Yamada
K
K
Sui
X
X
Tanaka
R
R
Nakahata
T
T
D000911:Antibodies, Monoclonal / Q000502:physiology; D018952:Antigens, CD34; D002455:Cell Division / Q000502:physiology; D016895:Culture Media, Serum-Free; D004247:DNA / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000494:pharmacology*; D007377:Interleukin-3 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D008533:Megakaryocytes / Q000166:cytology / Q000378:metabolism; D008938:Mitosis / Q000187:drug effects; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism; D017471:Receptors, Interferon / Q000378:metabolism; D019089:Stem Cell Factor / Q000494:pharmacology; D013926:Thrombopoietin / Q000276:immunology / Q000494:pharmacology*; D000096743:Interferon gamma Receptor
D000911:Antibodies, Monoclonal; D018952:Antigens, CD34; D016895:Culture Media, Serum-Free; D004247:DNA; D007371:Interferon-gamma; D007377:Interleukin-3; D015850:Interleukin-6; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D017471:Receptors, Interferon; D019089:Stem Cell Factor; D013926:Thrombopoietin; D000096743:Interferon gamma Receptor