ROLE OF ABERRANT SIALYLATION OF CHRONIC MYELOID-LEUKEMIA GRANULOCYTES ON BINDING AND SIGNAL-TRANSDUCTION BY CHEMOTACTIC PEPTIDES AND COLONY-STIMULATING FACTORS
ROLE OF ABERRANT SIALYLATION OF CHRONIC MYELOID-LEUKEMIA GRANULOCYTES ON BINDING AND SIGNAL-TRANSDUCTION BY CHEMOTACTIC PEPTIDES AND COLONY-STIMULATING FACTORS
复制标题
DOI：
10.3109/10428199309054733
复制
发表时间：
1993-09-01
影响因子：
2.6
通讯作者：
BAKER, M
中科院分区：
文献类型：
--
作者：
CYOPICK, P;CULLITON, R;BAKER, M
慢性粒细胞性白血病（CML）粒细胞表现出许多归因于未成熟粒细胞的特征，包括细胞表面糖蛋白唾液酸化的显着增加，这可能至少部分是由于胞苷5 '-一磷酸-N-乙酰神经氨酸：Ga 1 β 1 - 3Ga 1 NAcalpha（2-3）-唾液酸转移酶（EC 2.4.99.4）的活性增加，也可能是由于其他糖基转移酶和唾液酸酶的活性改变。CML粒细胞的这种异常唾液酸化导致合成趋化肽甲酰基Met Leu Phe（fMLP）与CML粒细胞表面的结合减少，这导致细胞溶质游离钙（[Ca 2 +]i）的快速、短暂增加，这是导致细胞活化的生化级联反应中的一个组成步骤。为了确定fMLP与CML粒细胞结合的减少是否转化为功能缺陷，我们测量了fMLP诱导的[Ca 2 +]i增加。与正常粒细胞相比，CML粒细胞中fMLP诱导的[Ca 2 +]i升高显著降低。唾液酸酶处理后，在CML粒细胞中观察到fMLP诱导的[Ca 2 +]i增加的显著增强，表明信号传导减少可能是异常唾液酸化的结果。为了确定异常唾液酸化的影响是否也改变内源性多肽介质的结合，我们确定了CML和正常粒细胞的去唾液酸化对粒细胞和单核细胞的集落刺激因子（殖民地GM-CSF）结合的影响，该因子在髓系细胞的分化和增殖中起作用。与fMLP结合一样，我们还发现，在唾液酸酶处理后，GM-CSF与CML粒细胞而不是正常粒细胞的结合显著增加。同样，GM-CSF与未分化HL-60细胞的结合在唾液酸酶处理后显著增加。因此，我们已经证明CML粒细胞的异常唾液酸化不仅改变了fMLP和GM-CSF与其受体的结合，而且还可能改变信号转导。因此，CML粒细胞的异常糖基化可能减少造血生长因子的结合，这反过来可能是导致CML粒细胞不成熟表型的原因。
Chronic myelogenous leukemia (CML) granulocytes exhibit a number of characteristics attributable to immature granulocytes, including marked increases in cell surface sialylation of glycoproteins which may be due, at least in part, to an increased activity of cytidine 5'-monophosphate-N-acetylneuraminic acid:Ga1beta1-3Ga1NAcalpha(2-3)-sialytransferase (EC 2.4.99.4), and perhaps to altered activity of other glycosyltransferases and sialidases. This aberrant sialylation of CML granulocytes contributes to the decreased binding of the synthetic chemotactic peptide, formyl Met Leu Phe (fMLP), to the surface of CML granulocytes which leads to a rapid, transient increase in cytosolic free calcium ([Ca2+]i), an integral step in the biochemical cascade leading to cell activation. To determine if the decrease in binding of fMLP to CML granulocytes translates into a functional deficit, we measured fMLP-induced increases in [Ca2+]i. Compared to normal granulocytes, fMLP-induced increases in [Ca2+]i were markedly decreased in CML granulocytes. After sialidase treatment, a significant augmentation in fMLP-induced increases in [Ca2+]i was noted in CML granulocytes, indicating that the decreased signalling may be a consequence of aberrant sialylation. To determine if the effects of aberrant sialylation also alters the binding of endogenous polypeptide mediators, we determined the effect of desialylation of CML and normal granulocytes on binding of the colony stimulating factor for granulocytes and monocytes (GM-CSF), which plays a role in differentiation and proliferation of myeloid-lineage cells. As with fMLP binding, we also showed that the binding of GM-CSF to CML granulocytes, but not normal granulocytes, was markedly increased after sialidase treatment. Similarly, binding of GM-CSF to undifferentiated HL-60 cells was markedly increased after sialidase treatment. Therefore, we have demonstrated that aberrant sialylation of CML granulocytes not only alters the binding of fMLP and GM-CSF to their receptor(s), but may also alter signal transduction. Thus, aberrant glycosylation of CML granulocytes may reduce the binding of hematopoietic growth factors, which in turn may be responsible for the immature phenotype of CML granulocytes.