Kodama H, Nose M, Niida S, Nishikawa S, Nishikawa S
Department of Anatomy, Ohu University School of Dentistry, Fukushima, Japan.
Exp Hematol. 1994 Sep;22(10):979-84.
The proto-oncogene c-kit, encoding a receptor-type tyrosine kinase, is allelic with the W locus of the mouse. The stromal cell line OP9, capable of supporting long-term hematopoiesis, was newly established from a newborn B6C3F1-op/op mouse calvaria. When bone marrow cells of WBB6F1-W/Wv mice were cocultured with the OP9 cells in liquid medium, hematopoiesis declined to a level one-thousandth of that in the cocultures of bone marrow cells of WBB6F1-+/+ mice and stromal cells by day 21. In contrast, when bone marrow cells of W/Wv mice were cocultured with OP9 cells in semisolid medium, at least 61% of the number of colonies were detected until the end of our observation period of 42 days when compared with that in control cocultures, although colonies formed by hematopoietic stem cells of W/Wv mice were significantly smaller than those of normal stem cells. After a 24-hour incubation with OP9 cells, fewer stem cells of W/Wv mice than normal ones adhered to the stromal cells. Adhesion of normal stem cells to stromal cells was inhibited by the addition of an antagonists anti-c-kit monoclonal antibody, ACK2. These results demonstrate that the c-kit receptor plays an important role not only in the proliferative response of hematopoietic stem cells but also in their adhesion to stromal cells.
原癌基因c-kit编码一种受体型酪氨酸激酶，与小鼠的W位点等位。能够支持长期造血的基质细胞系OP9是从新生的B6C3F1-op/op小鼠颅骨中新建的。当将WBB6F1-W/Wv小鼠的骨髓细胞与OP9细胞在液体培养基中共培养时，到第21天，造血功能下降到WBB6F1-+/+小鼠骨髓细胞与基质细胞共培养水平的千分之一。相反，当将W/Wv小鼠的骨髓细胞与OP9细胞在半固体培养基中共培养时，与对照共培养相比，在我们42天的观察期结束前至少检测到61%的集落数，尽管W/Wv小鼠造血干细胞形成的集落明显小于正常干细胞形成的集落。与OP9细胞孵育24小时后，W/Wv小鼠的干细胞比正常干细胞黏附到基质细胞上的数量更少。正常干细胞与基质细胞的黏附可被添加抗c-kit单克隆抗体ACK2拮抗剂所抑制。这些结果表明，c-kit受体不仅在造血干细胞的增殖反应中起重要作用，而且在其与基质细胞的黏附中也起重要作用。
