PMID- 18484240 OWN - NLM STAT- MEDLINE DCOM- 20090818 LR - 20211020 IS - 0925-5710 (Print) IS - 0925-5710 (Linking) VI - 88 IP - 1 DP - 2008 Jul TI - 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. PG - 64-72 LID - 10.1007/s12185-008-0098-z [doi] AB - 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. FAU - Saito, Yoshinobu AU - Saito Y AD - Department of Internal Medicine III, Akita University School of Medicine, Hondo 1-1-1, Akita, 010-8543, Japan. FAU - Guo, Yong Mei AU - Guo YM AD - Department of Internal Medicine III, Akita University School of Medicine, Hondo 1-1-1, Akita, 010-8543, Japan. FAU - Hirokawa, Makoto AU - Hirokawa M AD - Department of Internal Medicine III, Akita University School of Medicine, Hondo 1-1-1, Akita, 010-8543, Japan. FAU - Saito, Kunie AU - Saito K AD - Department of Internal Medicine III, Akita University School of Medicine, Hondo 1-1-1, Akita, 010-8543, Japan. FAU - Komatsuda, Atsushi AU - Komatsuda A AD - Department of Internal Medicine III, Akita University School of Medicine, Hondo 1-1-1, Akita, 010-8543, Japan. FAU - Takahashi, Naoto AU - Takahashi N AD - Department of Internal Medicine III, Akita University School of Medicine, Hondo 1-1-1, Akita, 010-8543, Japan. FAU - Fujishima, Masumi AU - Fujishima M AD - Department of Internal Medicine III, Akita University School of Medicine, Hondo 1-1-1, Akita, 010-8543, Japan. FAU - Fujishima, Naohito AU - Fujishima N AD - Department of Internal Medicine III, Akita University School of Medicine, Hondo 1-1-1, Akita, 010-8543, Japan. FAU - Yamashita, Junsuke AU - Yamashita J AD - Radioisotope Division, Bioscience center, Akita University Graduate School of Medicine, Akita, 010-8543, Japan. FAU - Sawada, Kenichi AU - Sawada K AD - 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. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20080520 PL - Japan TA - Int J Hematol JT - International journal of hematology JID - 9111627 RN - 0 (Antigens, CD34) RN - 0 (Antigens, Differentiation) RN - 0 (Tumor Necrosis Factor-alpha) RN - 143011-72-7 (Granulocyte Colony-Stimulating Factor) SB - IM MH - *Antigens, CD34 MH - Antigens, Differentiation/metabolism MH - Cell Culture Techniques MH - Cell Differentiation/drug effects/physiology MH - Cells, Cultured MH - Dendritic Cells/cytology/*metabolism MH - Granulocyte Colony-Stimulating Factor/*pharmacology MH - Granulocyte Precursor Cells/cytology/*metabolism MH - Humans MH - Megakaryocyte Progenitor Cells/cytology/*metabolism MH - Megakaryocytes/cytology/*metabolism MH - Neutrophils/cytology/*metabolism MH - Phagocytosis/*drug effects/physiology MH - Time Factors MH - Tumor Necrosis Factor-alpha/*pharmacology EDAT- 2008/05/20 09:00 MHDA- 2009/08/19 09:00 CRDT- 2008/05/20 09:00 PHST- 2008/01/29 00:00 [received] PHST- 2008/04/04 00:00 [accepted] PHST- 2008/03/09 00:00 [revised] PHST- 2008/05/20 09:00 [pubmed] PHST- 2009/08/19 09:00 [medline] PHST- 2008/05/20 09:00 [entrez] AID - 10.1007/s12185-008-0098-z [pii] AID - 10.1007/s12185-008-0098-z [doi] PST - ppublish SO - Int J Hematol. 2008 Jul;88(1):64-72. doi: 10.1007/s12185-008-0098-z. Epub 2008 May 20.