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 contained preformed IL-4. In contrast to cytolytic IL-4 release from calcium ionophore-activated eosinophils, eotaxin and RANTES, but not IFN-gamma, elicited IL-4 release by noncytotoxic mechanisms. With a dual Ab capture and detection 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 inhibitor of vesicle formation. Thus, CCR3-mediated signaling can rapidly mobilize IL-4 stored preformed in human eosinophils for release by vesicular transport to contribute to immune responses.
Bandeira-Melo
C
C
Department of Medicine, Harvard Thorndike Laboratories, Charles A. Dana Research Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
Sugiyama
K
K
Woods
L J
LJ
Weller
P F
PF
D054413:Chemokine CCL11; D019742:Chemokines, CC; D016207:Cytokines / Q000502:physiology*; D004804:Eosinophils / Q000276:immunology / Q000378:metabolism*; D005089:Exocytosis / Q000276:immunology; D005110:Extracellular Space / Q000276:immunology / Q000378:metabolism; D006801:Humans; D015847:Interleukin-4 / Q000096:biosynthesis / Q000378:metabolism*; D015848:Interleukin-5 / Q000502:physiology; D016209:Interleukin-8 / Q000502:physiology; D021381:Protein Transport / Q000276:immunology; D054397:Receptors, CCR3; D019707:Receptors, Chemokine / Q000502:physiology; D022161:Transport Vesicles / Q000276:immunology*
C515456:CCL11 protein, human; C515350:CCR3 protein, human; D054413:Chemokine CCL11; D019742:Chemokines, CC; D016207:Cytokines; D015848:Interleukin-5; D016209:Interleukin-8; D054397:Receptors, CCR3; D019707:Receptors, Chemokine; D015847:Interleukin-4