Cysteinyl leukotrienes induce IL-4 release from cord blood-derived human eosinophils

Background: Eosinophils contain preformed stores of IL-4 within their cytoplasmic granules, but physiologic stimuli to release IL-4 from eosinophils are not yet defined. Objective: We evaluated whether cysteinyl leukotrienes (CysLTs) could elicit IL-4 release from eosinophils. Methods: We used a dual-antibody capture and detection assay (EliCell) for IL-4 release and used eosinophils differentiated in vitro from human cord blood-derived progenitors. Results: Leukotriene (LT) C-4, LTD4, and LTE4 each elicited the rapid, vesicular transport-mediated, dose- and time-dependent release of IL-4 from eosinophils. Both LTD4 and LTE4 evoked similar and earlier IL-4 release than LTC4. LTC4 did not act directly but only after conversion to LTD4 because an inhibitor of gamma-glutamyl transpeptidase, acivicin, blocked LTC4-induced IL-4 release. MK571 and LY171833, receptor antagonists for CysLT(1) and not CysLT(2), and pertussis toxin inhibited LTC4-, LTD4-, and LTE4-indticed IL-4 release. Cord blood-differentiated eosinophils contained CysLT(1) protein detectable by means of immunoblotting. Conclusion: CysLTs acting through G(i) protein-coupled and MK571- and LY171833-inhibitable receptors on cord blood-derived human eosinophils can act as autocrine or paracrine mediators to stimulate the rapid, nonexocytotic release of preformed IL-4.