Multifaceted roles of cysteinyl leukotrienes in eliciting eosinophil granule protein secretion - PubMed (original) (raw)

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Multifaceted roles of cysteinyl leukotrienes in eliciting eosinophil granule protein secretion

Renata Baptista-dos-Reis et al. Biomed Res Int. 2015.

Abstract

Cysteinyl leukotrienes (cysLTs) are cell membrane-impermeant lipid mediators that play major roles in the pathogenesis of eosinophilic inflammation and are recognized to act via at least 2 receptors, namely, cysLT1 receptor (cysLT1R) and cysLT2 receptor (cysLT2R). Eosinophils, which are granulocytes classically associated with host defense against parasitic helminthes and allergic conditions, are distinguished from leukocytes by their dominant population of cytoplasmic crystalloid (also termed secretory, specific, or secondary) granules that contain robust stores of diverse preformed proteins. Human eosinophils are the main source of cysLTs and are recognized to express both cysLTs receptors (cysLTRs) on their surface, at the plasma membrane. More recently, we identified the expression of cysLTRs in eosinophil granule membranes and demonstrated that cysLTs, acting via their granule membrane-expressed receptors, elicit secretion from cell-free human eosinophil granules. Herein, we review the multifaceted roles of cysLTs in eliciting eosinophil granule protein secretion. We discuss the intracrine and autocrine/paracrine secretory responses evoked by cysLTs in eosinophils and in cell-free extracellular eosinophil crystalloid granules. We also discuss the importance of this finding in eosinophil immunobiology and speculate on its potential role(s) in eosinophilic diseases.

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Figures

Figure 1

Figure 1

CysLTs are intracrine signals regulating eosinophils' IL-4 secretion by piecemeal degranulation.IL-4 release induced by IL-16, eotaxin, and RANTES is dependent on the intracrine action of lipid body-generated LTC4. Inhibitors of 5-lypoxigenase (5-LO) and/or cysteinyl leukotriene receptors (cysLTRs) blocked intracellular LTC4 production and consequently IL-4 release from eosinophils. The cross-linking of LIR7- or CD9-induced perinuclear-generated LTC4, however IL-12 secretion induced by LIR7 or CD9 is independent of 5-LO metabolites. CysLT1R = cysLT1 receptor; cysLT2R = cysLT2 receptor, P2Y12R = purinergic P2Y12 receptor, and APLM = arachidonyl phospholipids and lipoxygenase machinery.

Figure 2

Figure 2

Stimulating cell-free eosinophil granules with the agonists LTC4, LTD4, and LTE4 elicited the secretion of eosinophil cationic protein (ECP) but not eosinophil-derived cytokines or chemokines from the granules. Cysteinyl leukotriene receptor (cysLTR) or P2Y12 receptor (P2Y12R) blockers inhibited ECP secretion after LTC4/LTD4/LTE4 stimulation of cell-free eosinophil granules.

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