Binding of interleukin-13 and interleukin-4 to the interleukin (IL)-4/IL-13 receptor of human synovial fibroblasts.

Synovial fibroblasts expressed transcripts for IL-4R alpha, and IL-13R alpha 1 and IL-13R alpha 2. Using weighted nonlinear computer modeling of the data from equilibrium binding studies, a 2 bindings sites model fitted the data best. After occupation of the shared high affinity receptors by the non-signaling, double mutant IL-4(121)R-->D, 124Y-->D (RY-IL-4) the high affinity binding of IL-13 could be abolished. A 2 binding site model still could be fitted, however the improvement in fit over a onesite model was not statistically significant. Using affinity spectra, at least 2 binding sites are apparent. After treatment with RY-IL-4, some of the high affinity binding was abolished, however not completely. A correlation between the number of binding sites and the affinity is apparent, which seriously casts doubt on the classical evaluation of binding isotherms, where the parameters are assumed to be independent. In a previous study we suggested that the large number of IL-13R alpha 2 monomers are silent receptors, likely representing a decoy target for IL-13. The high affinity binding therefore most likely represents the binding to the heterodimer consisting of IL-4R alpha and IL-13R alpha 1 or IL-13R alpha 2. The low affinity binding may represent the IL-13R alpha 2.