PMID- 16234354 OWN - NLM STAT- MEDLINE DCOM- 20060404 LR - 20210206 IS - 0006-4971 (Print) IS - 0006-4971 (Linking) VI - 107 IP - 4 DP - 2006 Feb 15 TI - Phagocytosis of codeveloping megakaryocytic progenitors by dendritic cells in culture with thrombopoietin and tumor necrosis factor-alpha and its possible role in hemophagocytic syndrome. PG - 1366-74 AB - Tumor necrosis factor-alpha (TNF-alpha) and thrombopoietin (TPO) have been shown to induce the differentiation and proliferation of CD34+ cells toward dendritic cells (DCs) in the presence of multiacting cytokines. We hypothesized that the costimulation of TPO and TNF-alpha generates megakaryocytic progenitors and DCs together from human CD34+ cells and that the interaction of these cells may indicate a physiologic and/or a pathologic role of DCs in megakaryopoiesis. When highly purified human CD34+ cells were cultured for 7 days with TPO alone, the generated cells expressed megakaryocytic markers, such as CD41, CD42b, and CD61. The addition of TNF-alpha with TPO remarkably decreased the number of megakaryocytic progenitor cells without affecting the cell yield. Almost half of the cells thus generated expressed CD11c, and most of them were positive for CD4 and CD123. Furthermore, CD11c+ cells were found to capture damaged CD61+ cells and to induce autologous T-cell proliferation, although the cytokine productions were low. We also confirmed an engulfment of CD61+ cells and their fragment by CD11c+ cells in bone marrow cells from patients with hemophagocytic syndrome. These findings suggest that DCs generated under megakaryocytic and inflammatory stimuli are involved in megakaryopoiesis and the subsequent immune responses to self-antigens. 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 - Hirokawa, Makoto AU - Hirokawa M FAU - Inaba, Kayo AU - Inaba K FAU - Fukaya, Hiroshi AU - Fukaya H FAU - Kawabata, Yoshinari AU - Kawabata Y FAU - Komatsuda, Atsushi AU - Komatsuda A FAU - Yamashita, Junsuke AU - Yamashita J FAU - Sawada, Kenichi AU - Sawada K LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20051018 PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (Antigens, CD) RN - 0 (Antigens, CD34) RN - 0 (Tumor Necrosis Factor-alpha) RN - 9014-42-0 (Thrombopoietin) SB - IM MH - Aged MH - Antigens, CD/blood MH - Antigens, CD34/blood MH - Cells, Cultured MH - Dendritic Cells/drug effects/*physiology MH - Female MH - Humans MH - Lymphohistiocytosis, Hemophagocytic/blood/immunology/*physiopathology MH - Male MH - Megakaryocytes/*cytology/drug effects/*physiology MH - Middle Aged MH - Phagocytosis MH - Thrombopoietin/*pharmacology MH - Tumor Necrosis Factor-alpha/*pharmacology EDAT- 2005/10/20 09:00 MHDA- 2006/04/06 09:00 CRDT- 2005/10/20 09:00 PHST- 2005/10/20 09:00 [pubmed] PHST- 2006/04/06 09:00 [medline] PHST- 2005/10/20 09:00 [entrez] AID - S0006-4971(20)66386-8 [pii] AID - 10.1182/blood-2005-08-3155 [doi] PST - ppublish SO - Blood. 2006 Feb 15;107(4):1366-74. doi: 10.1182/blood-2005-08-3155. Epub 2005 Oct 18.