Cytokine Receptor-Mediated Trafficking of Preformed IL-4 in Eosinophils Identifies an Innate Immune Mechanism of Cytokine Secretion
Although leukocytes of the innate immune system, including eosinophils, contain within their granules preformed stores of cytokines available for selective and rapid release, little is known about the mechanisms governing the mobilization and secretion of these cytokines. Here we show that a cytokin...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2006-02, Vol.103 (9), p.3333-3338 |
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| container_title | Proceedings of the National Academy of Sciences - PNAS |
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| creator | Spencer, Lisa A. Melo, Rossana C. N. Perez, Sandra A. C. Bafford, Staci P. Dvorak, Ann M. Weller, Peter F. |
| description | Although leukocytes of the innate immune system, including eosinophils, contain within their granules preformed stores of cytokines available for selective and rapid release, little is known about the mechanisms governing the mobilization and secretion of these cytokines. Here we show that a cytokine receptor, the IL-4 receptor α chain, mediates eotaxin-stimulated mobilization of preformed IL-4 from eosinophil granules into secretory vesicles. Eosinophils contain substantial intracellular quantities of several granule-and vesicle-associated cytokine receptors, including IL-4, IL-6, and IL-13 receptors as well as CCR3. Both IL-4 and IL-4 receptor α chain colocalized in eosinophil granules; and after eotaxinstimulation, IL-4 receptor α chain, bearing bound IL-4, was mobilized into secretory vesicles. These findings indicate that intracellular cytokine receptors within secretory vesicles transport their cognate cytokines requisite for the secretion of cytokines preformed in innate immune leukocytes. |
| doi_str_mv | 10.1073/pnas.0508946103 |
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N. ; Perez, Sandra A. C. ; Bafford, Staci P. ; Dvorak, Ann M. ; Weller, Peter F.</creator><creatorcontrib>Spencer, Lisa A. ; Melo, Rossana C. N. ; Perez, Sandra A. C. ; Bafford, Staci P. ; Dvorak, Ann M. ; Weller, Peter F.</creatorcontrib><description>Although leukocytes of the innate immune system, including eosinophils, contain within their granules preformed stores of cytokines available for selective and rapid release, little is known about the mechanisms governing the mobilization and secretion of these cytokines. Here we show that a cytokine receptor, the IL-4 receptor α chain, mediates eotaxin-stimulated mobilization of preformed IL-4 from eosinophil granules into secretory vesicles. Eosinophils contain substantial intracellular quantities of several granule-and vesicle-associated cytokine receptors, including IL-4, IL-6, and IL-13 receptors as well as CCR3. Both IL-4 and IL-4 receptor α chain colocalized in eosinophil granules; and after eotaxinstimulation, IL-4 receptor α chain, bearing bound IL-4, was mobilized into secretory vesicles. These findings indicate that intracellular cytokine receptors within secretory vesicles transport their cognate cytokines requisite for the secretion of cytokines preformed in innate immune leukocytes.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.0508946103</identifier><identifier>PMID: 16492782</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Biological Sciences ; Biology ; Cell membranes ; Cells, Cultured ; Chemokine CCL11 ; Chemokines ; Chemokines, CC - pharmacology ; Cytokine receptors ; Cytokines ; Cytometry ; Cytoplasm - metabolism ; Eosinophils ; Eosinophils - drug effects ; Eosinophils - metabolism ; Humans ; Immune system ; Immunity, Innate - immunology ; Immunology ; Interleukin-4 - immunology ; Interleukin-4 - metabolism ; Leukocytes ; Microscopy, Immunoelectron ; Protein Binding ; Protein Transport ; Receptors ; Receptors, CCR3 ; Receptors, Chemokine - immunology ; Receptors, Cytokine - immunology ; Receptors, Interleukin-4 - immunology ; Receptors, Interleukin-6 - metabolism ; Saponins ; Secretion ; Secretory vesicles</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2006-02, Vol.103 (9), p.3333-3338</ispartof><rights>Copyright 2006 National Academy of Sciences of the United States of America</rights><rights>Copyright National Academy of Sciences Feb 28, 2006</rights><rights>2006 by The National Academy of Sciences of the USA 2006</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c592t-c2688de627ebc0ab8682f423a7c3fc1e49af8dbeb6cb5f6851d5ace701a5ef083</citedby><cites>FETCH-LOGICAL-c592t-c2688de627ebc0ab8682f423a7c3fc1e49af8dbeb6cb5f6851d5ace701a5ef083</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/103/9.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/30048583$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/30048583$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,723,776,780,799,881,27901,27902,53766,53768,57992,58225</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16492782$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Spencer, Lisa A.</creatorcontrib><creatorcontrib>Melo, Rossana C. 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Eosinophils contain substantial intracellular quantities of several granule-and vesicle-associated cytokine receptors, including IL-4, IL-6, and IL-13 receptors as well as CCR3. Both IL-4 and IL-4 receptor α chain colocalized in eosinophil granules; and after eotaxinstimulation, IL-4 receptor α chain, bearing bound IL-4, was mobilized into secretory vesicles. 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| subjects | Biological Sciences Biology Cell membranes Cells, Cultured Chemokine CCL11 Chemokines Chemokines, CC - pharmacology Cytokine receptors Cytokines Cytometry Cytoplasm - metabolism Eosinophils Eosinophils - drug effects Eosinophils - metabolism Humans Immune system Immunity, Innate - immunology Immunology Interleukin-4 - immunology Interleukin-4 - metabolism Leukocytes Microscopy, Immunoelectron Protein Binding Protein Transport Receptors Receptors, CCR3 Receptors, Chemokine - immunology Receptors, Cytokine - immunology Receptors, Interleukin-4 - immunology Receptors, Interleukin-6 - metabolism Saponins Secretion Secretory vesicles |
| title | Cytokine Receptor-Mediated Trafficking of Preformed IL-4 in Eosinophils Identifies an Innate Immune Mechanism of Cytokine Secretion |
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