Oostendorp R A, Spitzer E, Dörmer P
GSF-Forschungszentrum für Umwelt und Gesundheit, Institut für Experimentelle Hämatologie, München, Deutschland.
Acta Haematol. 1996;95(3-4):243-7. doi: 10.1159/000203886.
It has been suggested that CD44 mediates adhesive interactions between hematopoietic progenitor cells and the stromal microenvironment. Ligands of CD44 include several extracellular matrix components, such as hyaluronic acid and fibronectin. Antibodies against CD44 have been shown to induce homotypic T cell aggregation, and to stimulate T and natural killer cell activity. We hypothesized that CD44 could similarly amplify interactions between blast-colony-forming cells and bone marrow stromal cells (BMSCs). Indeed, we have previously found that the anti-CD44 antibody NKI-P2 enhanced VLA-4-dependent interactions. Here, we studied an additional panel of nineteen anti-CD44 antibodies from the 5th Workshop on Leukocyte Differentiation antigens, to find out whether amplification was associated with a particular CD44 epitope. None of these antibodies showed inhibitory activity, whereas nine significantly increased the number of blast colonies more than 2-fold. Seven of these recognized epitope 1, and two epitope 2. More than 4-fold enhancement was only observed with epitope 1 antibodies: 4.C3 (4.4-fold), 212.3 (6.3-fold), L178 (9.1-fold), and NIH44-1 (9.2-fold). Our data suggest that primarily epitope 1 is associated with enhancement of colony formation. Furthermore, the findings support a role for CD44 as an amplifier in progenitor-BMSC interactions.
有人提出，CD44介导造血祖细胞与基质微环境之间的黏附相互作用。CD44的配体包括几种细胞外基质成分，如透明质酸和纤连蛋白。已证明抗CD44抗体可诱导同型T细胞聚集，并刺激T细胞和自然杀伤细胞活性。我们推测，CD44可能同样会增强原始集落形成细胞与骨髓基质细胞（BMSC）之间的相互作用。实际上，我们之前发现抗CD44抗体NKI-P2增强了VLA-4依赖性相互作用。在此，我们研究了来自第5届白细胞分化抗原研讨会的另外19种抗CD44抗体，以确定这种增强作用是否与特定的CD44表位相关。这些抗体均未显示出抑制活性，而其中9种抗体使原始集落数量显著增加了2倍以上。其中7种识别表位1，2种识别表位2。仅表位1抗体观察到超过4倍的增强作用：4.C3（4.4倍）、212.3（6.3倍）、L178（9.1倍）和NIH44-1（9.2倍）。我们的数据表明，主要是表位1与集落形成的增强相关。此外，这些发现支持CD44在祖细胞与BMSC相互作用中作为增强因子的作用。
