Sakane Naoki, Asano Yoko, Kawamura Tomoko, Takatani Tomohiro, Kohama Yasuhiro, Tsujikawa Kazutake, Yamamoto Hiroshi
Department of Immunology, Graduate School of Pharmaceutical Sciences, Osaka University, Japan.
Biol Pharm Bull. 2004 Dec;27(12):2014-20. doi: 10.1248/bpb.27.2014.
Fetal liver (FL) hematopoiesis is thought to be important for expanding the cell number during ontogeny. In order to investigate the cellular interaction molecules among FL stromal and hematopoietic cells, we established a monoclonal antibody, Ndk-10, that reacts with FL stromal cells but not with dish non-adherent cells. When Ndk-10 was added to an FL stromal and hematopoietic cell-coculture, it inhibited the survival of c-kit+ cells. The inhibitory activity of Ndk-10 was also observed in the fetal liver organ culture. The Ndk-10 recognized a 150 kD molecule in the adherent cells of FL and kidney, and the N-terminal amino acid sequence was identical to that of mouse aminopeptidase N/CD13. The peptidase activity of CD13 was inhibited by Ndk-10, and addition of its specific inhibitor resulted in the same inhibitory activity as Ndk-10. We propose that aminopeptidase N/CD13 is a critical molecule that regulates the survival of c-kit+ cells in the FL microenvironment.
胎儿肝脏(FL)造血被认为在个体发育过程中对细胞数量的扩增很重要。为了研究FL基质细胞和造血细胞之间的细胞相互作用分子,我们制备了一种单克隆抗体Ndk - 10,它能与FL基质细胞反应,但不与培养皿中的非贴壁细胞反应。当将Ndk - 10添加到FL基质细胞和造血细胞共培养体系中时,它会抑制c - kit⁺细胞的存活。在胎儿肝脏器官培养中也观察到了Ndk - 10的抑制活性。Ndk - 10识别FL和肾脏贴壁细胞中的一种150 kD分子,其N端氨基酸序列与小鼠氨肽酶N/CD13相同。CD13的肽酶活性被Ndk - 10抑制,添加其特异性抑制剂会产生与Ndk - 10相同的抑制活性。我们提出氨肽酶N/CD13是调节FL微环境中c - kit⁺细胞存活的关键分子。