Leukotriene receptor antagonists inhibit secretion, even from extracellular eosinophil granules
Montelukast inhibits stimulatory actions of cysteinyl leukotrienes, as currently recognized by principally blocking a single cysteinyl leukotriene receptor (CysLT1R) expressed on surface membranes of cells, including eosinophils, a class of leukocytes associated with allergic diseases. In eosinophil-associated diseases lysis of eosinophils releases free, intact, membranebound granules; however, the functional capacities of these extracellular eosinophil granules and their pertinence to allergic diseases have never been defined. Neves et al (p 477), writing in this issue of the Journal, document that cell-free human eosinophil granules express on their granule surface membranes ligand-binding domains for 2 cysteinyl leukotriene receptors and a purinergic receptor responsive to cysteinyl leukotrienes and demonstrate that cysteinyl leukotrienes, including those formed extracellularly, stimulate isolated eosinophil granules to secrete eosinophil cationic protein. Moreover, montelukast and a purinergic receptor antagonist that blocks the same receptor as does clopidogrel inhibited secretion of eosinophil cationic protein from eosinophil granules. These findings not only demonstrate that extracellular eosinophil granules in sites of allergic inflammation are secretion-competent organelles but also indicate that therapeutics, such as montelukast, might be beneficial not solely by acting on a single receptor (CysLT1R) expressed on intact cells but also by acting more broadly on other cysteinyl leukotriene receptors, including those expressed on cell-free eosinophil granules in sites of allergic inflammation. Read the full article here.

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