Mechanisms of AllergyCysteinyl leukotrienes induce IL-4 release from cord blood–derived human eosinophils☆,☆☆
Section snippets
In vitro derivation of eosinophils
Eosinophils were differentiated in vitro from human placental cord blood-derived progenitors, as previously described.10 Briefly, mononuclear-enriched cells were cultured on a 1-mm layer of Matrigel (Becton-Dickinson) in supplemented RPMI-1640 medium containing 350 pmol/L rhIL-3 and 200 pmol/L rhIL-5 (Peprotech). Nonadherent cells were passed weekly. Complete eosinophil differentiation was ascertained by means of morphologic analysis of Wright- and Giemsa-stained cells. As previously defined,10
Results
We used human eosinophils derived in vitro from IL-3- and IL-5-stimulated cord blood progenitors to evaluate whether CysLTs might function as autocrine-paracrine activators to elicit IL-4 release from eosinophils. As previously described,10, 12, 13 at week 4 of incubation with IL-3/IL-5 in a Matrigel bed, virtually all progenitor cells developed from mononuclear cells into mature eosinophils. These in vitro-derived eosinophils contain eosinophilic granules and mRNA transcripts for
Discussion
The capacity of eosinophils to release their granule-stored IL-4 by means of a regulated, nonexocytotic process of vesicular transport would enable this TH2 cytokine to be rapidly secreted in the tissue environments around appropriately activated eosinophils. To date, the CC chemokines eotaxin and RANTES are the only physiologic stimuli recognized to elicit the vesicular transport-mediated release of preformed IL-4 from eosinophils.9 Prior studies had identified nonphysiologic stimuli, such as
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Supported by National Institutes of Health grants AI20241, AI22571, AI41995, and HL56386.
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Reprint requests: Peter F. Weller, MD, Beth Israel Deaconess Medical Center, DA-617, 330 Brookline Ave, Boston, MA 02215.