Phagocytosis of co-developing neutrophil progenitors by dendritic cells in a culture of human CD34(+) cells with granulocyte colony-stimulating factor and tumor necrosis factor-alpha.
Tumor necrosis factor-alpha (TNF-alpha) has been shown to induce the differentiation of CD34(+) cells toward dendritic cells (DCs). We have previously shown that DCs are co-generated from human CD34(+) cells during erythroid or megakaryocytic differentiation in the presence of TNF-alpha, and those DCs are able to stimulate autologous T cell proliferation. The aim of this study was to learn whether the co-stimulation of granulocyte colony-stimulating factor (G-CSF) and TNF-alpha would generate neutrophil progenitors and DCs together from human CD34(+) cells, and if this was the case, to clarify the phenotypic and functional characteristics of these DCs. When highly purified human CD34(+) cells were cultured for 7 days with G-CSF alone, the generated cells predominantly expressed a granulocyte marker, CD15, and then differentiated into neutrophils after 14 days of culture. The addition of TNF-alpha with G-CSF markedly decreased the number of CD15(+) cells without affecting the total number of cells during 7 days of culture. Almost one third of the generated cells were positive for CD11c and CD123. Furthermore, CD11c(+) cells were found to phagocytose CD15(+) cells and were able to induce allogeneic, but not autologous, T cell proliferation in the mixed lymphocyte reaction (MLR). On the other hand, the CD11c(+) cells generated by TNF-alpha and cytokines capable of inducing erythroid differentiation were able to stimulate autologous T cells. There was a difference in the expression of CD80, CD83 and CD86 among CD11c(+) cells induced by G-CSF plus TNF-alpha and those generated by interleukin-3, stem cell factor, and erythropoietin plus TNF-alpha. These results indicate that the co-stimulation of human CD34(+) cells with G-CSF and TNF-alpha induces the phagocytosis of co-developing neutrophil progenitors by DCs, and the stimulatory effects of these DCs on autologous T cells is different from that of DCs generated from CD34(+) cells during erythroid differentiation.
Saito
Yoshinobu
Y
Department of Internal Medicine III, Akita University School of Medicine, Hondo 1-1-1, Akita, 010-8543, Japan.
Guo
Yong Mei
YM
Department of Internal Medicine III, Akita University School of Medicine, Hondo 1-1-1, Akita, 010-8543, Japan.
Hirokawa
Makoto
M
Department of Internal Medicine III, Akita University School of Medicine, Hondo 1-1-1, Akita, 010-8543, Japan.
Saito
Kunie
K
Department of Internal Medicine III, Akita University School of Medicine, Hondo 1-1-1, Akita, 010-8543, Japan.
Komatsuda
Atsushi
A
Department of Internal Medicine III, Akita University School of Medicine, Hondo 1-1-1, Akita, 010-8543, Japan.
Takahashi
Naoto
N
Department of Internal Medicine III, Akita University School of Medicine, Hondo 1-1-1, Akita, 010-8543, Japan.
Fujishima
Masumi
M
Department of Internal Medicine III, Akita University School of Medicine, Hondo 1-1-1, Akita, 010-8543, Japan.
Fujishima
Naohito
N
Department of Internal Medicine III, Akita University School of Medicine, Hondo 1-1-1, Akita, 010-8543, Japan.
Yamashita
Junsuke
J
Radioisotope Division, Bioscience center, Akita University Graduate School of Medicine, Akita, 010-8543, Japan.
Sawada
Kenichi
K
Department of Internal Medicine III, Akita University School of Medicine, Hondo 1-1-1, Akita, 010-8543, Japan. ksawada@doc.med.akita-u.ac.jp.
D018952:Antigens, CD34; D000943:Antigens, Differentiation / Q000378:metabolism; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism*; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D042381:Granulocyte Precursor Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D055016:Megakaryocyte Progenitor Cells / Q000166:cytology / Q000378:metabolism*; D008533:Megakaryocytes / Q000166:cytology / Q000378:metabolism*; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism*; D010587:Phagocytosis / Q000187:drug effects* / Q000502:physiology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D018952:Antigens, CD34; D000943:Antigens, Differentiation; D014409:Tumor Necrosis Factor-alpha; D016179:Granulocyte Colony-Stimulating Factor