Rösel M, Khaldoyanidi S, Zawadzki V, Zöller M
Department of Tumor Progression and Immune Defense, German Cancer Research Center, Heidelberg.
Exp Hematol. 1999 Apr;27(4):698-711. doi: 10.1016/s0301-472x(98)00082-4.
CD44 has been described repeatedly to be involved in hematopoiesis. Here, we addressed the question of functional activity of CD44 variant isoform v10 (CD44v10) in progenitor cell maturation by in vivo and in vitro blocking studies with a monoclonal antibody and a receptor globulin. We became interested in this question by the observation that CD44v10 is expressed, although at a low level, on a subpopulation of bone marrow cells. Flow cytometry revealed that 15%-20% of hematopoietic cells in the fetal liver and 25%-35% of bone marrow cells in adult mice were CD44v10 positive. The majority of CD44v10+ cells was HSA+/J11d+ and CD43+. CD44v10 was not detected on CD4+, CD8+, IgM+, or IgD+ cells. A CD44v10 receptor globulin did not bind to hematopoietic progenitor cells, but to stromal elements. The CD44v10-CD44v10 ligand interaction had a major impact on the adhesion of progenitor cells to stromal elements. When healthy animals received repeated injections of either anti CD44v10 or the CD44v10 receptor globulin, committed progenitors were mobilized and significantly augmented numbers were recovered in the spleen and the peripheral blood. Furthermore, the CD44v10-CD44v10 ligand interaction, which had no impact on progenitor expansion, influenced progenitor maturation, particularly of the B-cell lineage. Although the nature of the CD44v10 ligand remains to be explored, the supportive role of CD44v10 in progenitor maturation and, importantly, the efficient mobilization of progenitor cells by anti-CD44v10 and a CD44v10 receptor globulin could be of clinical benefit in peripheral blood stem cell transplantation.
CD44已被多次描述参与造血过程。在此,我们通过使用单克隆抗体和受体球蛋白进行体内和体外阻断研究,探讨了CD44变异体同工型v10(CD44v10)在祖细胞成熟中的功能活性问题。我们对这个问题产生兴趣是因为观察到CD44v10在骨髓细胞亚群中表达,尽管表达水平较低。流式细胞术显示,胎肝中15%-20%的造血细胞以及成年小鼠骨髓中25%-35%的细胞CD44v10呈阳性。大多数CD44v10+细胞为HSA+/J11d+和CD43+。在CD4+、CD8+、IgM+或IgD+细胞上未检测到CD44v10。一种CD44v10受体球蛋白不与造血祖细胞结合,但与基质成分结合。CD44v10-CD44v10配体相互作用对祖细胞与基质成分的黏附具有重大影响。当健康动物反复注射抗CD44v10或CD44v10受体球蛋白时,定向祖细胞被动员起来,脾脏和外周血中回收的数量显著增加。此外,对祖细胞扩增没有影响的CD44v10-CD44v10配体相互作用影响祖细胞成熟,尤其是B细胞谱系的成熟。尽管CD44v10配体的性质仍有待探索,但CD44v10在祖细胞成熟中的支持作用,以及重要的是抗CD44v10和CD44v10受体球蛋白对祖细胞的有效动员,可能在外周血干细胞移植中具有临床益处。