Cytokines recognizing GPI-anchored glycan

据报道，多种细胞因子能够识别特定的碳水化合物部分。研究发现，IL-1β、TNF-α、IL-18等细胞因子都能识别GPI锚定的糖链。（1）甘露糖6-磷酸或磷脂酰肌醇特异性磷脂酶C（PI-PLC）可抑制TNF-α诱导的人淋巴瘤U937细胞凋亡。这些结果表明，在U937细胞中，TNF-α与GPI锚定聚糖的结合，沿着其与TNF-α受体的结合，触发了细胞内信号传导途径。（ii）发现IL-18和IL-18 R α分别通过GPI聚糖的第三个甘露糖6-磷酸二酯和第二个β-GlcNAc缺失的甘露糖6-磷酸结合。为了研究IL-18的碳水化合物识别是否参与生理活性，在IL-18刺激之前用PI-PLC消化KG-1细胞。PI-PLC处理抑制酪氨酸激酶的磷酸化和随后的IL-18依赖性IFN-γ的产生。IL-18刺激KG-1细胞后，IL-18 R α亚单位与CD 48发生免疫沉淀。这些观察结果表明，IL-18/IL-18 R α/CD 48通过肽部分和GPI聚糖形成复合物触发了与IL-18 R β的结合，并且IL-18/IL-18 R α/CD 48/IL-18 R β复合物诱导细胞信号传导。

A variety of cytokines have been reported to be able to recognize specific carbohydrate moieties. I have found that several cytokines including IL-1β,TNF-α,IL-18 can recognize GPI-anchored glycan. In this research, I investigated whether the carbohydrate recognition by these cytokines can modulate their physiological activities, (i)The stimulation of the apoptosis o human lymphoma U937 cells by TNF-α was inhibited by treatment with mannose 6-phosphate or phosphatidyl inositol-speciic phospholipase C (PI-PLC). These results suggest that TNF-α bindig to the GPI-anchore glycan, along with its binding to TNF-α receptor, triggers the intracellular signaling pathway in U937 cells, (ii)I found that IL-18 and IL-18Rα bind to GPI glycan via the third mannose 6-phosphate diester and the second β-GlcNAc-deleted mannose 6-phosphate of GPI-glycan, respectively. To investigate whether the carbohydrate recognition of IL-18 is involved in physiological activities, KG-1 cells were digested with PI-PLC before IL-18 stimulation. PI-PLC treatment inhibited the phosphorylation of tyrosine kinases and the following IL-18 dependent IFN-γ production. Moreover, IL-18Receptor α subunit of IL-18 stimulated KG-1 cells was immunoprecipitated together CD48 by anti-IL-18Rα antibody. These observations suggest that the complex formation of IL-18/IL-18Rα/CD48 via both the peptide portion and GPI glycan triggers the binding to IL-18Rβ, and IL-18/IL-18Rα/CD48/IL-18Rβ complex induces cellular signaling.