IL-1β scavenging by the type IIIL-1 decoy receptor in human neutrophils
IL-1β scavenging by the type IIIL-1 decoy receptor in human neutrophils
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DOI：
10.4049/jimmunol.170.12.5999
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发表时间：
2003-06-15
影响因子：
4.4
通讯作者：
Mantovani, A
中科院分区：
文献类型：
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作者：
Bourke, E;Cassetti, A;Mantovani, A
IL-1通过结合由IL-1 RI和辅助蛋白IL-1 RAcPr组成的异源二聚体受体发挥其细胞效应。此外，它与IL-1 RII结合，而IL-1 RII缺乏信号传导功能，被认为是诱饵作用。在主要表达（>90%）IL-1 RII的人多形核白细胞（PMN）中检测配体与诱饵受体相互作用后的命运。PMN与IL-1 β孵育导致细胞表面相关配体迅速减少，同时伴随着内化IL-1的增加，在37 ℃下1小时内50-60%的IL-1 β位于细胞内。阻断抗体的使用揭示了IL-1内化仅由诱饵受体介导。抑制剂分析的结果表明，内化需要ATP的合成，并涉及网格蛋白介导的内吞，是。去除配体后，受体在细胞表面迅速重新表达。蛋白质合成抑制剂环己脲对该过程没有影响，表明重新表达的受体被回收。此外，用IL-1 RII稳定转染的人角质形成细胞（HaCAT 811）也内化IL-1 RII，90分钟后43%的细胞表面受体内化。免疫荧光显微镜显示内化受体与麦胚凝集素标记的内化糖蛋白和早期内体Ag-1共定位，早期内体Ag-1是与早期内体区室相关的蛋白质，表明细胞通过内吞作用摄取IL-1 RII。相反，在其他免疫来源的细胞中观察到很少或没有内化。这些结果表明，诱饵受体IL-1 RII可以作为IL-1的清道夫，代表一种新的IL-1系统的自动调节机制。
IL-1 elicits its cellular effects by binding a heterodimeric receptor consisting of IL-1RI and the accessory protein, IL-1RAcPr. In addition, it binds to IL-1RII, which lacking signaling function has been ascribed a decoy role. The fate of the ligand following interaction with the decoy receptor was examined in human polymorphonuclear cells (PMN), which express predominantly (>90%) IL-1RII. Incubation of PMN with IL-1beta results in a rapid decrease in cell surface-associated ligand accompanied by a concomitant increase in internalized IL-1 with 50-60% of IL-1beta located intracellularly within 1 h at 37degreesC. The use of blocking Abs revealed that IL-1 internalization is mediated exclusively by the decoy receptor. The results of inhibitor analysis demonstrate that internalization requires ATP synthesis and involves clathrin-mediated endocytos,is. Following removal of the ligand, the receptor was rapidly re-expressed on the cell surface. Cyclohexamide, a protein synthesis inhibitor, had no effect upon the process, suggesting that the re-expressed receptor was recycled. In addition, human keratinocytes stably transfected with IL-1RII (HaCAT 811) also internalized the IL-1RII with 43% cell surface receptor internalized after 90 min. Immunofluorescence microscopy revealed colocalization of the internalized receptor with wheat germ agglutinin-labeled internalized glycoproteins and early endosome Ag-1, a protein associated with the early endosome compartments, indicative of cellular uptake of IL-1RII by endocytosis. In contrast, little or no internalization was observed in other cells of immune origin. These results suggest that the decoy receptor IL-1RII can act as a scavenger of IL-1, representing a novel autoregulatory mechanism of the IL-1 system.