title: Eosinophil granules function extracellularly as receptor-mediated secretory organelles.
abstract: Intracellular granules in several types of leukocytes contain preformed proteins whose secretions contribute to immune and inflammatory functions of leukocytes, including eosinophils, cells notably associated with asthma, allergic inflammation, and helminthic infections. Cytokines and chemokines typically elicit extracellular secretion of granule proteins by engaging receptors expressed externally on the plasma membranes of cells, including eosinophils. Eosinophil granules, in addition to being intracellular organelles, are found as intact membrane-bound structures extracellularly in tissue sites of eosinophil-associated diseases. Neither the secretory capacities of cell-free eosinophil granules nor the presence of functional cytokine and chemokine receptors on membranes of leukocyte granules have been recognized. Here, we show that granules of human eosinophils express membrane receptors for a cytokine, IFN-gamma, and G protein-coupled membrane receptors for a chemokine, eotaxin, and that these receptors function by activating signal-transducing pathways within granules to elicit secretion from within granules. Capacities of intracellular granule organelles to function autonomously outside of eosinophils as independent, ligand-responsive, secretion-competent structures constitute a novel postcytolytic mechanism for regulated secretion of eosinophil granule proteins that may contribute to eosinophil-mediated inflammation and immunomodulation.
authors.affiliation: Department of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Josiane S
authors.initials: JS
authors.lastname: Neves
authors.forename: Sandra A C
authors.initials: SA
authors.lastname: Perez
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Spencer
authors.forename: Rossana C N
authors.initials: RC
authors.lastname: Melo
authors.forename: Lauren
authors.initials: L
authors.lastname: Reynolds
authors.forename: Ionita
authors.initials: I
authors.lastname: Ghiran
authors.forename: Salahaddin
authors.initials: S
authors.lastname: Mahmudi-Azer
authors.forename: Solomon O
authors.initials: SO
authors.lastname: Odemuyiwa
authors.forename: Ann M
authors.initials: AM
authors.lastname: Dvorak
authors.forename: Redwan
authors.initials: R
authors.lastname: Moqbel
authors.forename: Peter F
authors.initials: PF
authors.lastname: Weller
mesh_terms: D015153:Blotting, Western; D020126:Brefeldin A / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D003594:Cytoplasmic Granules / Q000502:physiology*; D004804:Eosinophils / Q000187:drug effects / Q000648:ultrastructure*; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000502:physiology; D046529:Microscopy, Electron, Transmission; D015388:Organelles / Q000502:physiology*; D015398:Signal Transduction
chemical_list: D016207:Cytokines; D020126:Brefeldin A; D007371:Interferon-gamma