期刊
JOURNAL OF IMMUNOLOGY
卷 171, 期 12, 页码 6574-6580出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.171.12.6574
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- NHLBI NIH HHS [HL68743] Funding Source: Medline
- NIAID NIH HHS [AI15614] Funding Source: Medline
Steady state mRNA levels in various human tissues reveal that the proinflammatory cytokine IL-18 is constitutively and ubiquitously expressed. However, limited IL-18R alpha-chain (IL-18Ralpha) expression in tissues may restrict ligand-acting sites and contribute to a specific response for IL-18. To study the IL-18R complex, [I-125]IL-18 was studied for binding to the cell surface receptors of IL-18-responsive NK and macrophagic KG-1 cells. After cross-linking, [I-125]IL-18 formed three IL-18R complexes with sizes of approximately 93, 160, and 220 kDa. In KG-1 cells, Scatchard analysis revealed the presence of 135 binding sites/cell, with an apparent dissociation constant (K-d) of 250 pM; in NK cells, there were 350 binding sites per cell with an apparent Kd of 146 pM. Each domain of extracellular IL-18Ra was cloned and individually expressed in Escherichia coli. An mAb specifically recognized the membrane-proximal third domain; this mAb blocked IL-18-induced IFN-gamma production in NK cells. Furthermore, deletion of the membrane-proximal third domain of IL-18Ra prevented the formation of IL-18R ternary complex with IL-18R beta-chain. The present studies demonstrate that the biologically active IL-18R complex requires the membrane-proximal third Ig-like domain in IL-18Ra for the formation of IL-18R ternary complex as well as for signal transduction involved in IL-18-induced IFN-gamma in NK cells.
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