Binding of sialyl Lewis X antigen to lectin-like receptors on NK cells induces cytotoxicity and tyrosine phosphorylation of a 17-kDa protein
Binding of sialyl Lewis X antigen to lectin-like receptors on NK cells induces cytotoxicity and tyrosine phosphorylation of a 17-kDa protein
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DOI：
10.1016/j.bbagen.2006.03.015
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发表时间：
2006-09-01
影响因子：
3
通讯作者：
Matsumoto, Kojiro
中科院分区：
文献类型：
--
作者：
Higai, Koji;Ichikawa, Akihiro;Matsumoto, Kojiro
背景：自然杀伤（NK）细胞通过细胞表面受体（包括凝集素样受体）介导细胞毒性。我们使用人肝癌来源的 HepG2 细胞 (Hep-TF) 分泌的转铁蛋白（其 N 聚糖富含1,3-岩藻糖基化的双触角、三触角和四触角型复合物，以及市售的人转铁蛋白 (Nor-TF)，其由双触角 N-聚糖组成，无 α 1,3-岩藻糖基化。结果：从岩藻糖基转移酶 3 转染细胞中分离出的高 sLeX 表达的冷白血病衍生 K562 细胞对 KEYG 细胞的敏感性比野生型 K562 细胞高 2.5 倍。异硫氰酸荧光素 (FITC) 标记的 Hep-TF 与 KHYG 细胞的结合强度是 FITC 标记的 Nor-TF 的 1.8 倍；用抗 NKG2D、抗 NKG2C、抗 CD94 和抗 CD161 抗体治疗可抑制该结合。与野生型 U937 细胞相比，FITC 标记的 Hep-TF 与转染 NKG2D 和 CD94 的人单核细胞衍生的 U937 细胞的结合更强。此外，KHYG 细胞中 17-kDa 蛋白的酪氨酸磷酸化通过在 Hep-TF 包被的板上孵育并用抗 NKG2D 抗体处理而增强，但通过 Nor-TF 包被的板和抗 CD94 抗体处理则不增强。结论：sLe(X) 抗原与 NK 细胞上的凝集素样受体相互作用，诱导通过酪氨酸磷酸化 17-kDa 蛋白介导的细胞毒性。 (c) 2006 Elsevier B.V. 保留所有权利。
Background: Natural killer (NK) cells mediate cytotoxicity through cell-surface receptors including lectin-like receptors. We have investigated whether sialyl Lewis X (sLe(X)) antigen, Neu5Ac alpha 2,3Gal beta 1,4(Fuc alpha 1,3) GlcNAc-R, can bind to the lectin-like receptors on human NK-derived KHYG cells, using transferrin secreted by human hepatoma-derived HepG2 cells (Hep-TF), whose N-glycans are rich in a 1,3-fucosylated bi-, tri-, and tetra-antennary type complexes, and commercially available human transferrin (Nor-TF), which is comprised of bi-antermary N-glycans without alpha 1,3-fucosylation. Results: High sLeX-expressing crythroleukemia-derived K562 cells isolated from fucosyltransferase-3-transfected cells were 2.5-fold more susceptible than wild-type K562 cells to KEYG cells. Fluorescein isothiocyanate (FITC)-labeled Hep-TF bound 1.8-fold more strongly to KHYG cells than did FITC-labeled Nor-TF; the binding was suppressed by treatment with anti-NKG2D, anti-NKG2C, anti-CD94 and anti-CD161 antibodies. FITC-labeled Hep-TF bound more strongly to human monocyte-derived U937 cells transfected with NKG2D and CD94 than to wild-type U937 cells. Moreover, tyrosine phosphorylation of a 17-kDa protein in the KHYG cells was enhanced by incubation on a Hep-TF coated plate and treatment with an anti-NKG2D antibody, but not by a Nor-TF coated plate and an anti-CD94 antibody. Conclusion: The interaction of sLe(X) antigen with lectin-like receptors on NK cells induces cytotoxicity that is mediated through a tyrosine-phosphorylated 17-kDa protein. (c) 2006 Elsevier B.V. All rights reserved.