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Eosinophil granules are notable for their content of preformed proteins whose secretion underlies many of the contributions eosinophils make in allergic and anthelminthic responses. We have recently shown that cell-free eosinophil granules respond to eotaxin and IFN-γ via cognate signaling-coupled granule membrane-expressed receptors, triggering phosphorylation of intragranular signaling molecules and eliciting specific secretion of granule-derived proteins. Thus, fully intact eosinophil granules deposited extracellularly within diseased tissues maintain a capacity to function as secretory competent organelles, demanding a fresh look at our understanding of the secretion of eosinophil granule-derived proteins, both intracellularly and extracellularly. Here, we review a series of our recent work revealing the unique ultrastructure of human eosinophil granules and mechanisms of intragranule sorting and mobilization of specific cytokine products from intact human eosinophils. Implications of these findings t...