Two different functions for CD44 proteins in human myelopoiesis.
Two different functions for CD44 proteins in human myelopoiesis.
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DOI：
10.1172/jci2494
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发表时间：
1998-09
期刊：
影响因子：
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通讯作者：
J. Moll;Sophia K. Khaldoyanidi;Jonathan P. Sleeman;M. Achtnich;I. Preuss;H. Ponta;P. Herrlich
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文献类型：
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作者：
J. Moll;Sophia K. Khaldoyanidi;Jonathan P. Sleeman;M. Achtnich;I. Preuss;H. Ponta;P. Herrlich
CD 44在骨髓生成过程中是重要的，尽管变体CD 44蛋白的贡献尚不清楚。我们在此表明，在人长期骨髓培养中，识别CD 44 NH 2-末端表位（mAb 25-32）或CD 44 v6表位（mAb VFF 18）的抗体抑制骨髓生成。然而，单抗25-32而非单抗VFF 18影响骨髓集落形成。这些数据表明，早期前体细胞区室是25-32抗体的靶标，而mAb VFF 18靶向骨髓生成的后期阶段。由于大部分造血前体细胞对v6表位呈阴性，并且只有一小部分髓样细胞表达v6表位，因此我们使用了几种人髓样祖细胞系来阐明不同CD 44蛋白的功能。这些细胞系在向髓样分化刺激时产生变体CD 44蛋白，主要是新的变体CD 44 v4-v10。通过表达CD 44 v4-v10可以获得的特征是透明质酸（HA）和从头硫酸软骨素A（CS-A）结合增加。尽管CD 44 v4-v10本身的表达对于HA和CS-A结合是必需的，但蛋白质骨架似乎需要适当的糖基化。HA结合导致CD 44介导的细胞自聚集和粘附至基质细胞系MS-5。总之，我们的数据表明，不同的CD 44蛋白是重要的，至少有两个不同的步骤，骨髓。
CD44 is important during myelopoiesis, although the contributions of variant CD44 proteins are unclear. We show here that in human long-term bone marrow culture antibodies recognizing a CD44 NH2-terminal epitope (mab 25-32) or a CD44v6 epitope (mab VFF18) inhibit myelopoiesis. However, mab 25-32 but not mab VFF18 affects myeloid colony formation. These data suggest that an early precursor cell compartment is the target for the 25-32 antibody, whereas the mab VFF18 targets later stages in myelopoiesis. Since the bulk of hemopoietic precursor cells are negative for the v6 epitope and only a minor subset of myeloid cells express the v6 epitope, we have used several human myeloid progenitor cell lines to unravel the function of different CD44 proteins. These cell lines produce variant CD44 proteins, predominantly a new variant CD44v4-v10, when stimulated towards myeloid differentiation. Features that can be acquired by the expression of CD44v4-v10 are an increased hyaluronate (HA) and a de novo chondroitin sulphate A (CS-A) binding. Although, the expression of CD44v4-v10 per se is necessary for HA and CS-A binding, the protein backbone seems to require appropriate glycosylation. HA binding results in CD44-mediated cellular self-aggregation and adhesion to the stromal cell line MS-5. In summary, our data suggest that different CD44 proteins are important for at least two different steps in myelopoiesis.