Smadja-Joffe F, Legras S, Girard N, Li Y, Delpech B, Bloget F, Morimoto K, Le Bousse-Kerdiles C, Clay D, Jasmin C, Levesque J P
Unite d'Oncogenese Appliquee, Inserm U268, Hopital Paul Brousse, Villejuif, France.
Leuk Lymphoma. 1996 May;21(5-6):407-20, color plates following 528. doi: 10.3109/10428199609093438.
The CD44 cell surface molecule has been shown to be the principal cell surface receptor for hyaluronan (or hyaluronic acid), a glycosaminoglycan component of marrow extracellular matrix. However, its affinity for hyaluronan is not constitutive, since it depends on the cell type, the stage of differentiation and on activation by external stimuli including certain anti-CD44 antibodies and phorbol esters. Except for a few lymphoid cell lines, hematopoietic cells do not spontaneously bind hyaluronan and initial studies reported that, contrary to lymphocytes, myeloid cells could not be activated to bind hyaluronan. Because CD44 plays an important role in the initial phases of hematopoiesis, as shown by experiments using blocking anti-CD44 monoclonal antibodies, its capacity to mediate adhesion of primitive myeloid cells has been investigated. It was found that CD44 could mediate spontaneous adhesion to hyaluronan of immature myeloid cell lines KG1, KG1a, and TF1, which serve as a model for hematopoietic progenitors. However, despite expressing high amounts of CD44, no more than 15% of bone marrow progenitors could adhere to hyaluronan. Recent experiments have shown that a very important feature of CD44 is its capacity to be rapidly activated by certain antibodies and cytokines (GM-CSF and KL) from a low affinity to a high affinity state for hyaluronan. These data shed light on striking similarities in the functional regulation of CD44 and of the two integrin receptors VLA-4 (a4b1), and VLA-5 (a5b1), which are also expressed on hematopoietic progenitors. The relevance of these data to the regulation of normal hematopoiesis and mobilization of CD34+ progenitors in the view of cell grafting is analyzed. In addition, we show that in idiopathic myelofibrosis, the amount of hyaluronan is markedly increased in the extracellular matrix from the myeloproliferative spleen. Considering that the production of cytokines is enhanced in this disease, we discuss whether CD44-hyaluronan interaction may have a role in the pathophysiology of this myeloproliferative syndrome.
CD44细胞表面分子已被证明是透明质酸（或透明质酸）的主要细胞表面受体，透明质酸是骨髓细胞外基质的一种糖胺聚糖成分。然而，它对透明质酸的亲和力并非固有，因为它取决于细胞类型、分化阶段以及包括某些抗CD44抗体和佛波酯在内的外部刺激的激活。除了少数淋巴细胞系外，造血细胞不会自发结合透明质酸，并且最初的研究报告称，与淋巴细胞相反，髓样细胞不能被激活以结合透明质酸。由于使用阻断性抗CD44单克隆抗体的实验表明CD44在造血的初始阶段发挥重要作用，因此对其介导原始髓样细胞黏附的能力进行了研究。发现CD44可以介导未成熟髓样细胞系KG1、KG1a和TF1与透明质酸的自发黏附，这些细胞系可作为造血祖细胞的模型。然而，尽管表达大量的CD44，但不超过15%的骨髓祖细胞能够黏附于透明质酸。最近的实验表明，CD44的一个非常重要的特征是它能够被某些抗体和细胞因子（GM-CSF和KL）迅速激活，从对透明质酸的低亲和力状态转变为高亲和力状态。这些数据揭示了CD44与两种整合素受体VLA-4（α4β1）和VLA-5（α5β1）在功能调节上的惊人相似之处，这两种受体也在造血祖细胞上表达。分析了这些数据在细胞移植方面对正常造血调节和CD34+祖细胞动员的相关性。此外，我们表明在特发性骨髓纤维化中，骨髓增殖性脾脏的细胞外基质中透明质酸的量显著增加。考虑到这种疾病中细胞因子的产生增加，我们讨论了CD44-透明质酸相互作用是否可能在这种骨髓增殖综合征的病理生理学中起作用。
