Expression of CD175 (Tn), CD175s (sialosyl-Tn) and CD176 (Thomsen-Friedenreich antigen) on malignant human hematopoietic cells
Expression of CD175 (Tn), CD175s (sialosyl-Tn) and CD176 (Thomsen-Friedenreich antigen) on malignant human hematopoietic cells
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DOI：
10.1002/ijc.23493
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发表时间：
2008-07-01
影响因子：
6.4
通讯作者：
Schwartz-Albiez, Reinhard
中科院分区：
文献类型：
--
作者：
Cao, Yi;Merling, Anette;Schwartz-Albiez, Reinhard
用流式细胞术、免疫组织学和免疫沉淀等方法分析了组织血型碳水化合物结构T-nouvelle （Tn, CD175）、唾液化To （CD175s）和Thomsen-Friedenreich双糖（TF, CD176）在人白血病细胞株上的表达。用抗CD176抗体比较免疫染色法评价唾液酸酶治疗前后唾液酸化CD176的表达。虽然只有少数细胞系表达未被掩盖的CD176，但唾液化的CD176存在于所有造血细胞系和天然淋巴细胞中。CD175和CD175在红母细胞白血病细胞系中优先表达。CD175s在这些细胞中的表达与编码关键酶α 2,6-唾液基转移酶（hST6GalNAc1）的基因的转录一致。细胞经甲醇预处理后，染色强度降低，表明这些聚糖部分表达为鞘糖脂成分。免疫沉淀和随后的Western blotting显示了一系列不同的高分子糖蛋白作为这些碳水化合物抗原的载体。通过免疫沉淀和微测序，在富集CD176表达的KG-1亚系上鉴定出CD34是CD176的主要载体。用抗cd176抗体孵育几种cd176阳性细胞系可诱导这些细胞凋亡，而抗cd175 / cd175抗体未观察到这种作用。由于天然存在的抗cd176抗体可能代表了一种针对cd176阳性肿瘤细胞的免疫监视机制，我们提出表面表达的cd176的唾液化以及其他功能可以防止细胞凋亡。(C) 2008 Wiley-Liss, Inc。
The expression of the histo-blood group carbohydrate structures T-nouvelle (Tn, CD175), sialylated To (CD175s) and the Thomsen-Friedenreich disaccharide (TF, CD176) on human leukemia cell lines was analyzed by their reactivity with specific monoclonal antibodies in flow cytometry, immunohistology and immunoprecipitation. Expression of sialylated CD176 was evaluated by comparative immunostaining with anti-CD176 antibodies before and after sialidase treatment. While only few cell lines expressed unmasked CD176, sialylated CD176 was present on all hematopoietic cell lines and native lymphocytes examined. CD175 and CD175s are preferentially expressed on erythroblastic leukemia cell lines. CD175s expression in these cells is consistent with the transcription of the gene encoding the key enzyme alpha 2,6-sialyltransferase (hST6GalNAc1). The staining intensity was reduced after methanol pretreatment of cells, indicating that these glycans are partially expressed as constituents of glycosphingolipids. Immunoprecipitation and subsequent Western blotting revealed a series of distinct high molecular glycoproteins as carriers for these carbohydrate antigens. CD34 was identified as major carrier of CD176 by immunoprecipitation and microsequencing on a KG-1 subline enriched for CD176 expression. Incubation of several CD176-positive cell lines with anti-CD176 antibodies induced apoptosis of these cells, an effect not observed with anti-CD175/CD175s antibodies. Since the presence of naturally occurring anti-CD176 antibodies may represent a mechanism of immunosurveillance against CD176-positive tumor cells, we propose that sialylation of surface-expressed CD176-among other functions-protects against apoptosis. (C) 2008 Wiley-Liss, Inc.