IL-1β scavenging by the type II IL-1 decoy receptor in human neutrophils

Emer Bourke, Arianna Cassetti, Antonello Villa, Emma Fadlon, Francesco Colotta, Alberto Mantovani

Research output: Contribution to journalArticlepeer-review

Abstract

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-1RH. Incubation of PMN with IL-1β results in a rapid decrease in cell surface-associated ligand accompanied by a concomitant increase in internalized IL-1 with 50-60% of IL-1β located intracellularly within 1 h at 37°C. 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 endocytosis. 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.

Original languageEnglish
Pages (from-to)5999-6005
Number of pages7
JournalJournal of Immunology
Volume170
Issue number12
Publication statusPublished - Jun 15 2003

ASJC Scopus subject areas

  • Immunology

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