Evidence that natural murine soluble interleukin 4 receptors may act as transport proteins.

作者：Rafael Fernandez-Botrán, E S Vitetta · 发表于：The Journal of Experimental Medicine · 年份：1991 · DOI：10.1084/jem.174.3.673 · 被引用次数：97 · 研究领域：Immune Cell Function and Interaction、Toxin Mechanisms and Immunotoxins、Transgenic Plants and Applications

The present studies were undertaken to determine whether the interleukin 4 binding proteins (IL-4BPs) previously identified in the biological fluids of mice are soluble forms of IL-4Rs. We also studied the binding properties of IL-4BPs in order to gain insight into their physiological role in vivo. Affinity-purified IL-4BPs and recombinant soluble IL-4Rs generated similar one-dimensional (Cleveland) peptide maps after digestion with either Staphylococcus aureus V8 protease or trypsin, indicating structural similarities. Furthermore, a rat mAb directed against the murine IL-4Rs immunoprecipitated the IL-4BPs and completely inhibited binding of 125I-IL-4 to a purified preparation of IL-4BPs. Taken together these data indicate that the IL-4BPs are soluble IL-4Rs. At 4 degrees C the IL-4BPs competitively inhibited the binding of IL-4 to membrane IL-4Rs but their ability to prevent binding of IL-4 to cells at 37 degrees C, at the same concentrations, was significantly reduced. Kinetic binding studies of soluble IL-4BPs vs. membrane IL-4Rs disclosed important differences in their rates of dissociation from IL-4. Whereas dissociation at 4 degrees C was slow for both, dissociation of IL-4 from IL-BPs at 37 degrees C was considerably faster (t 1/2 of 2 min) than dissociation of IL-4 from membrane IL-4Rs (t 1/2 of approximately 69 min). Temperature-dependent changes in dissociation kinetics were reversible, and could not be accounted for by either inactivation of the IL-4BPs at 37 degr...