CD44-mediated adhesiveness of human hematopoietic progenitors to hyaluronan is modulated by cytokines
CD44-mediated adhesiveness of human hematopoietic progenitors to hyaluronan is modulated by cytokines
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DOI：
10.1182/blood.v89.6.1905
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发表时间：
1997-03-15
期刊：
影响因子：
20.3
通讯作者：
SmadjaJoffe, F
中科院分区：
文献类型：
--
作者：
Legras, S;Levesque, JP;SmadjaJoffe, F
CD34(+)造血祖细胞(HPC)和骨髓基质之间的粘附相互作用对于正常造血至关重要，但其分子基础仍不清楚。我们研究了细胞表面蛋白聚糖CD44是否可以介导人CD34(+) HPC与固定化透明质酸(HA)（骨髓细胞外基质中丰富的糖胺聚糖）的粘附。我们的数据表明，尽管CD34(+)细胞强烈表达CD44，但只有13.3+/-1.1%自发粘附到HA。短期甲基纤维素测定显示HA粘附的CD34(+)细胞包含粒单核细胞和红系定型祖细胞(分别占输入的19.6%+/-2.5%和7.3%+/-1.0%)。更原始的祖细胞，例如前集落形成单位，也粘附于HA。此外，我们发现佛波醇12-肉豆蔻酸酯乙酸酯（PMA）、功能激活抗CD44单克隆抗体H90以及粒细胞-单核细胞集落刺激因子、白介素-3（IL-3）和干细胞因子等细胞因子可以增强CD44介导的CD34+细胞与HA的粘附。通过 PMA 的增强需要几个小时，是蛋白质合成依赖性的，并且与 CD44 细胞表面表达的增加有关，而 H90 单克隆抗体和细胞因子对粘附的刺激非常迅速，并且不改变 CD44 表达。 H90 诱导的激活发生在 4 摄氏度，并持续至少 2 小时，而细胞因子的激活需要在 37 摄氏度下孵育，并且是短暂的。这些数据首次表明CD34(+) HPC可以通过CD44直接粘附HA，指出这种与HA的粘附相互作用是一个也可能受到细胞因子生理调节的过程。 (C) 1997 年，美国血液学会。
Adhesive interactions between CD34(+) hematopoietic progenitor cells (HPC) and bone marrow stroma are crucial for normal hematopoiesis, yet their molecular bases are still poorly elucidated. We have investigated whether cell surface proteoglycan CD44 can mediate adhesion of human CD34(+) HPC to immobilized hyaluronan (HA), an abundant glycosaminoglycan of the bone marrow extracellular matrix, Our data show that, although CD34(+) cells strongly express CD44, only 13.3+/-1.1% spontaneously adheres to HA. Short-term methylcellulose assay showed that HA-adherent CD34(+) cells comprised granulo-monocytic and erythroid committed progenitors (19.6%+/-2.5% and 7.3%+/-1.0% of the input, respectively). More primitive progenitors, such as pre-colony-forming units, also adhered to HA. Moreover, we found that CD44-mediated adhesion of CD34(+) cells to HA could be enhanced by phorbol 12-myristate It-acetate (PMA), the function-activating anti-CD44 monoclonal antibody H90, and cytokines such as granulocyte-monocyte colony-stimulating factor, interleukin-3 (IL-3), and stem cell factor. Enhancement through PMA required several hours, was protein-synthesis-dependent, and was associated with an increase of CD44 cell surface expression, whereas stimulation of adhesion by H90 monoclonal antibody and cytokines was very rapid and without alteration of CD44 expression. H90-induced activation occurred at 4 degrees C and lasted for at least 2 hours, whereas activation by cytokines required incubation at 37 degrees C and was transient. These data, which show for the first time that CD34(+) HPC can directly adhere to HA via CD44, point out that this adhesive interaction to HA is a process that may also be physiologically regulated by cytokines. (C) 1997 by The American Society of Hematology.