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Sclerotium rolfsii lectin induces opposite effects on normal PBMCs and leukemic Molt-4 cells by recognising TF antigen and its variants as receptors
Glycoconjugate Journal ( IF 3 ) Pub Date : 2020-01-04 , DOI: 10.1007/s10719-019-09905-y
Vishwanath B Chachadi 1 , Radha Pujari 2 , Padma Shastry 2 , Bale M Swamy 1 , Shashikala R Inamdar 1
Affiliation  

Sclerotium rolfsii lectin (SRL) exerts apoptotic effect against various cancer cells and an antitumor activity on mice with colon and breast cancer xenografts. The current study aimed to explore its exquisite carbohydrate specificity on human peripheral blood mononuclear cells (PBMCs) and leukemic T-cells. SRL, showed strong binding (>98%) to resting/activated PBMCs, leukemic Molt-4 and Jurkat cell lines. The glycans mediated binding to these cells was effectively blocked by mucin and fetuin, exhibiting 97% and 94% inhibition respectively. SRL showed mitogenic stimulation of PBMCs at 10 μg/ml as determined by thymidine incorporation assay. In contrast, lectin induced a dose dependent growth inhibition of Molt-4 cells with 58% inhibition at 25 μg/ml. Many common membrane receptors in activated PBMCs, Molt 4 and Jurkat cells were identified by lectin blotting. However, membrane receptors that are recognized by SRL in normal resting PBMCs were totally different and are high molecular weight glycoproteins. Treatment of membrane receptors with glycosidases prior to lectin probing, revealed that fucosylated Thomsen–Friedenreich(TF) antigen glycans are increasingly expressed on transformed Molt-4 leukemic cells compared to other cells. The findings highlight the opposite effects of SRL on transformed and normal hematopoietic cells by recognizing different glycan-receptors. SRL has promising potential for diagnostics and therapeutic applications in leukaemia.

中文翻译:

罗氏菌菌凝集素通过将TF抗原及其变体识别为受体,对正常PBMC和白血病Molt-4细胞产生相反的作用

菌核病凝集素(SRL)对各种癌细胞具有凋亡作用,并对结肠癌和乳腺癌异种移植小鼠具有抗肿瘤活性。当前的研究旨在探索其对人外周血单核细胞(PBMC)和白血病T细胞的精湛的碳水化合物特异性。SRL表现出与静止/激活的PBMC,白血病Molt-4和Jurkat细胞系的强结合力(> 98%)。粘蛋白和胎球蛋白有效阻断了聚糖介导的与这些细胞结合的结合,分别表现出97%和94%的抑制作用。SRL显示,通过胸苷掺入法测定,PBMC有丝分裂刺激为10μg/ ml。相反,凝集素在25μg/ ml时对Molt-4细胞具有剂量依赖性的生长抑制作用,抑制率为58%。通过凝集素印迹鉴定了活化的PBMC,Molt 4和Jurkat细胞中的许多常见膜受体。但是,正常静止的PBMC中被SRL识别的膜受体是完全不同的,并且是高分子量糖蛋白。在凝集素探测之前用糖苷酶处理膜受体,发现与其他细胞相比,岩藻糖基化的Thomsen-Friedenreich(TF)抗原聚糖在转化的Molt-4白血病细胞上越来越多地表达。这些发现通过识别不同的聚糖受体突显了SRL对转化的造血细胞和正常造血细胞的相反作用。SRL在白血病的诊断和治疗应用方面具有广阔的潜力。结果表明,与其他细胞相比,岩藻糖基化的Thomsen-Friedenreich(TF)抗原聚糖在转化的Molt-4白血病细胞上越来越多地表达。这些发现通过识别不同的聚糖受体突显了SRL对转化的造血细胞和正常造血细胞的相反作用。SRL在白血病的诊断和治疗应用方面具有广阔的潜力。结果表明,与其他细胞相比,岩藻糖基化的Thomsen-Friedenreich(TF)抗原聚糖在转化的Molt-4白血病细胞上越来越多地表达。这些发现通过识别不同的聚糖受体突显了SRL对转化的造血细胞和正常造血细胞的相反作用。SRL在白血病的诊断和治疗应用方面具有广阔的潜力。
更新日期:2020-01-04
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