Delfino D V, Patrene K D, DeLeo A B, DeLeo R, Herberman R B, Boggs S S
Department of Radiation Oncology, University of Pittsburgh School of Medicine, PA 15261.
J Immunol. 1994 Jun 1;152(11):5171-9.
The role of the adhesion molecule CD44 in the development of NK cells was analyzed in a mouse long-term bone marrow culture system. After 4 wk of culture (day 0), recombinant human IL-2 was added and 13 days later the cells generated were shown to have substantial cytotoxic activity against YAC-1 and to be enriched for NK cells, as assessed for NK-1.1 phenotype by flow cytometric analysis. Physical separation between stroma and precursors partially inhibited proliferation and, consequently, a lower number of cytotoxic cells were produced. Similar results were obtained when an anti-CD44 mAb was added together with IL-2 at day 0. The disruption of hyaluronic acid (HA), one of the ligands of CD44, by hyaluronidase or the competition for the binding of CD44 by soluble HA added with IL-2 on day 0 inhibited both proliferation and development of cytotoxicity to a greater degree than did anti-CD44. These results indicate that interaction of CD44 with HA plays an important role in the development of pre-NK cells into cytotoxic effector cells.
在小鼠长期骨髓培养系统中分析了黏附分子CD44在自然杀伤（NK）细胞发育中的作用。培养4周（第0天）后，添加重组人白细胞介素-2（IL-2），13天后，通过流式细胞术分析NK-1.1表型评估，所产生的细胞显示出对YAC-1细胞具有显著的细胞毒性活性，并且富含NK细胞。基质与前体细胞之间的物理分离部分抑制了增殖，因此产生的细胞毒性细胞数量减少。当在第0天与IL-2一起添加抗CD44单克隆抗体时，也获得了类似的结果。透明质酸酶破坏CD44的配体之一透明质酸（HA），或在第0天与IL-2一起添加可溶性HA竞争CD44的结合，比抗CD44更能抑制增殖和细胞毒性的发展。这些结果表明，CD44与HA的相互作用在NK前体细胞发育为细胞毒性效应细胞的过程中起重要作用。
