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) 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.


CONCLUSIONS
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.
Bandeira-Melo
Christianne
C
Division of Allergy and Inflammation, Beth Israel Deaconess Medical Center, Boston, Mass 02215, USA.
Hall
John C
JC
Penrose
John F
JF
Weller
Peter F
PF
D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D003545:Cysteine / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D004804:Eosinophils / Q000187:drug effects / Q000378:metabolism*; D005312:Fetal Blood / Q000166:cytology*; D006801:Humans; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D015847:Interleukin-4 / Q000097:blood*; D007555:Isoxazoles / Q000494:pharmacology; D017997:Leukotriene C4 / Q000008:administration & dosage / Q000494:pharmacology; D017998:Leukotriene D4 / Q000008:administration & dosage / Q000494:pharmacology; D017999:Leukotriene E4 / Q000008:administration & dosage / Q000494:pharmacology; D015289:Leukotrienes / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D008565:Membrane Proteins; D008856:Microscopy, Fluorescence; D037342:Pertussis Toxin; D011422:Propionates / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D011817:Rabbits; D018077:Receptors, Leukotriene / Q000378:metabolism; D013777:Tetrazoles / Q000494:pharmacology; D013997:Time Factors; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D000098:Acetophenones; D018836:Inflammation Mediators; D007555:Isoxazoles; D015289:Leukotrienes; D008565:Membrane Proteins; D011422:Propionates; D011804:Quinolines; D018077:Receptors, Leukotriene; D013777:Tetrazoles; D010566:Virulence Factors, Bordetella; C112381:cysteinyl-leukotriene; D015847:Interleukin-4; D017997:Leukotriene C4; C059141:verlukast; D017998:Leukotriene D4; D017999:Leukotriene E4; C044660:LY 171883; C412375:cysteinyl leukotriene receptor 2; D037342:Pertussis Toxin; D003545:Cysteine; C083169:leukotriene D4 receptor; C006303:acivicin