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.
journal_name
Proc Natl Acad Sci U S Aauthors
Neves JS,Perez SA,Spencer LA,Melo RC,Reynolds L,Ghiran I,Mahmudi-Azer S,Odemuyiwa SO,Dvorak AM,Moqbel R,Weller PFdoi
10.1073/pnas.0804547105subject
Has Abstractpub_date
2008-11-25 00:00:00pages
18478-83issue
47eissn
0027-8424issn
1091-6490pii
0804547105journal_volume
105pub_type
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