L-Selectin Expression is Influenced by Phosphatase Activity in Chronic Lymphocytic LeukemiaKey terms
L-Selectin Expression is Influenced by Phosphatase Activity in Chronic Lymphocytic LeukemiaKey terms
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DOI：
10.1002/cyto.b.21771
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发表时间：
2019-03-01
影响因子：
3.4
通讯作者：
Kappelmayer, Janos
中科院分区：
文献类型：
--
作者：
Debreceni, Ildiko Beke;Szasz, Robert;Kappelmayer, Janos
背景粘附受体在细胞侵袭中起重要作用，而L-选择素是慢性淋巴细胞白血病（CLL）细胞与内皮细胞上几种糖基化蛋白结合的主要决定因素。我们调查L-选择素的表达CLL细胞，并探讨其机制，导致其shedding.Methods表面和可溶性L-选择素的表达水平，分别用流式细胞术和免疫测定法进行了研究。磁分离的B细胞从患者和对照组进行了研究，总的和蛋白磷酸酶-2A的活动。结果CLL患者外周血淋巴细胞绝对计数升高，可溶性L-选择素高表达，表面L-选择素低表达。同样，与正常B细胞相比，B-CLL细胞的TACE表面表达显着较低。与正常B细胞相比，B-CLL细胞中的总磷酸酶和蛋白磷酸酶-2A活性也显著较低，因此我们发现B-CLL细胞中pp 38 MAPK的水平较高。基于在体外实验中的MAPK抑制剂可以减弱磷酸酶抑制剂的L-选择素shedding.Conclusions磷酸酶活性较低的慢性淋巴细胞白血病检测，结果在下游信号级联与随后减少表面L-选择素的表达，这种效果是由增强磷酸化p38 MAPK和改变TACE表达介导的。(c)2019年，任作家。细胞计数B部分：Wiley Periodicals，Inc.出版的临床细胞计数。国际临床细胞计数学会（International Clinical Cytometry Society）
Background Adhesion receptors have important role in cellular invasiveness and L-selectin is a primary determinant in the binding of chronic lymphocytic leukemia (CLL) cells to several glycated proteins on endothelial cells. We investigated L-selectin expression on CLL cells and explored the mechanisms that lead to their shedding.Methods Surface and soluble L-selectin expression levels were studied by flow cytometry and immunoassay, respectively. Magnetically isolated B-cells from patients and controls were investigated for total and protein phosphatase-2A activities. Flow cytometry of permeabilized cells was utilized for the determination of phosphorylated mitogen-activated protein kinase (pp38MAPK) and surface tumor necrosis factor alpha-converting enzyme expression (TACE).Results In CLL patients elevated absolute lymphocyte cell counts, high soluble and low surface L-selectin expression were observed. Similarly, TACE surface expression was significantly lower on B-CLL cells compared to normal B-cells. Both total phosphatase and protein phosphatase-2A activities were also significantly lower in B-CLL cells compared to normal B-cells and we found a consequently higher level of pp38 MAPK in B-CLL cells. Based on in vitro experiments a MAPK inhibitor could attenuate the phosphatase inhibitor's effect on L-selectin shedding.Conclusions The lower phosphatase activity detectable in chronic lymphocytic leukemia, results in a downstream signaling cascade with subsequent reduction of surface L-selectin expression and this effect is mediated by enhanced phosphorylation of p38MAPK and an altered TACE expression. (c) 2019 The Authors. Cytometry Part B: Clinical Cytometry published by Wiley Periodicals, Inc. on behalf of International Clinical Cytometry Society.