Cutting edge: Eotaxin elicits rapid vesicular transport-mediated release of preformed IL-4 from human eosinophils

IL-4 release is important in promoting Th2-mediated allergic and parasitic immune responses. Although human eosinophils are potential sources of IL-4, physiologic mechanisms to elicit its release have not been established. By flow cytometry and microscopy, eosinophils from normal donors uniformly co ntained preformed IL-4. In contrast to cytolytic IL-4 release from calcium ionophore-activated eosinophils, eotaxin and RANTES, but not IFN-gamma, eli cited IL-4 release by noncytotoxic mechanisms. With a dual Ab capture and d etection immunofluorescent microscopic assay, IL-4 was released at discrete cell surface sites. IL-5 enhanced eotaxin-induced IL-4 release, which was mediated by G protein-coupled CCR3 receptors, detectable as early as 5 min and maximum within 1 h. IL-4 release was not diminished by transcription or protein synthesis inhibitors, but was suppressed by brefeldin A, an inhibi tor of vesicle formation. Thus, CCR3-mediated signaling can rapidly mobiliz e IL-4 stored preformed in human eosinophils for release by vesicular trans port to contribute to immune responses.