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J Allergy Clin Immunol. 2002 Jun;109(6):975-9.

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

Author information

1
Division of Allergy and Inflammation, Beth Israel Deaconess Medical Center, Boston, Mass 02215, USA.

Abstract

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) C4, 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 CysLT1 and not CysLT2, and pertussis toxin inhibited LTC4-, LTD4-, and LTE4-induced IL-4 release. Cord blood-differentiated eosinophils contained CysLT1 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.

PMID:
12063527
DOI:
10.1067/mai.2002.124269
[Indexed for MEDLINE]

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