Open AccessNotch ligand Delta‐1 differentially modulates the effects of gp130 activation on interleukin‐6 receptor α‐positive and ‐negative human hematopoietic progenitors
Author(s) -
Yamamura Kentaro,
Ohishi Kohshi,
Katayama Naoyuki,
Kato Keizo,
Shibasaki Tetsunori,
Sugimoto Yuka,
Miyata Eri,
Shiku Hiroshi,
Masuya Masahiro,
Nishioka Junji,
Nobori Tsutomu,
Nishikawa Mitsuo,
Inagaki Yoshimasa,
Hiramatsu Hidefumi,
Nakahata Tatsutoshi
Publication year - 2007
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2007.00566.x
Subject(s) - haematopoiesis , progenitor cell , biology , cd38 , interleukin 3 , microbiology and biotechnology , myeloid , cd34 , t cell , stem cell , immunology , immune system , antigen presenting cell
Interleukin (IL)‐6 plays pleiotropic roles in human hematopoiesis and immune responses by acting on not only the IL‐6 receptor‐α subunit (IL‐6Rα) + but also IL‐6Rα − hematopoietic progenitors via soluble IL‐6R. The Notch ligand Delta‐1 has been identified as an important modulator of the differentiation and proliferation of human hematopoietic progenitors. Here, it was investigated whether these actions of IL‐6 are influenced by Delta‐1. When CD34 + CD38 − hematopoietic progenitors were cultured with stem cell factor, flt3 ligand, thrombopoietin and IL‐3, Delta‐1, in combination with the IL‐6R/IL‐6 fusion protein FP6, increased the generation of glycophorin A + erythroid cells but counteracted the effects of IL‐6 and FP6 on the generation of CD14 + monocytic and CD15 + granulocytic cells. Although freshly isolated CD34 + CD38 − cells expressed no or only low levels of IL‐6Rα, its expression was increased in myeloid progenitors after culture but remained negative in erythroid progenitors. It was found that Delta‐1 acted in synergy with FP6 to enhance the generation of erythroid cells from the IL‐6Rα − erythroid progenitors. In contrast, Delta‐1 antagonized the effects of IL‐6 and FP6 on the development of monocytic and granulocytic cells, as well as CD14 − CD1a + dendritic cells, from the IL‐6Rα + myeloid progenitors. These results indicate that Delta‐1 interacts differentially with gp130 activation in IL‐6Rα − erythroid and IL‐6Rα + myeloid progenitors. The present data suggest a divergent interaction between Delta‐1 and gp130 activation in human hematopoiesis. ( Cancer Sci 2007; 98: 1597–1603)