Suppressive effects of swainsonine and N-butyldeoxynojirimycin on human bone marrow neutrophil maturation.
The effects of the N-linked oligosaccharide inhibitors swainsonine and N-butyldeoxynojirimycin (NB-DNJ) on granulopoiesis was investigated using human bone marrow cells in in vitro liquid and agar cultures. The addition of the inhibitors into cultures containing granulocyte colony-stimulating factor (G-CSF) suppressed maturation from myelocytes into mature neutrophils. Swainsonine did not induce apoptosis, but NB-DNJ induced considerable apoptosis, especially in the presence of G-CSF. This result indicated that the decrease of mature neutrophils by swainsonine was not because of cell degeneration. In the case of NB-DNJ, it was thought to be because of both maturation suppression and apoptosis. In a colony-forming unit-granuloid (CFU-G) colony assay, the number of colonies was increased in the presence of the inhibitors, but the morphology of colonies was predominantly compact, or immature. The inhibitors also suppressed the expressions of mRNAs of CCAAT/enhancer binding protein epsilon (C/EBPepsilon) and G-CSF receptor as markers of terminal neutrophil maturation. These findings suggested that the incompleteness of N-linked oligosaccharide leads to the suppression of terminal neutrophil maturation.
Misago
M
M
Laboratory of Clinical Hematology, School of Health Sciences, University of Occupational and Environmental Health, Kitakyushu, 807-8555, Japan. misago@med.uoeh-u.ac.jp
Tsukada
J
J
Fukuda
M N
MN
Eto
S
S
D017485:1-Deoxynojirimycin / Q000031:analogs & derivatives* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001483:Base Sequence; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D022762:CCAAT-Enhancer-Binding Proteins; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D065089:Glycoside Hydrolase Inhibitors; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D006410:Hematopoiesis / Q000187:drug effects; D006801:Humans; D008361:Mannosidases / Q000037:antagonists & inhibitors; D009504:Neutrophils / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics; D009844:Oligosaccharides / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000235:genetics; D017026:Swainsonine / Q000494:pharmacology*; D014415:Tunicamycin / Q000494:pharmacology; D043323:alpha-Mannosidase
D022762:CCAAT-Enhancer-Binding Proteins; D017931:DNA Primers; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D065089:Glycoside Hydrolase Inhibitors; D009687:Nuclear Proteins; D009844:Oligosaccharides; D012333:RNA, Messenger; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D014415:Tunicamycin; D016179:Granulocyte Colony-Stimulating Factor; D017485:1-Deoxynojirimycin; C059896:miglustat; D008361:Mannosidases; D043323:alpha-Mannosidase; D017026:Swainsonine