| Human eosinophils recognize endogenous danger signal crystalline uric acid and produce proinflammatory cytokines mediated by autocrine ATP. | |
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MedLine Citation:
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PMID: 20483787 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Eosinophils are multifunctional leukocytes involved in various inflammatory processes, as well as tissue remodeling and immunoregulation. During inflammation and infection, injured cells and damaged tissues release uric acid and monosodium urate (MSU) crystals as important endogenous danger signals. Uric acid is also implicated in the immunogenic effects of an authentic Th2 adjuvant, aluminum hydroxide. Eosinophils often localize at sites of Th2-type chronic inflammation; therefore, we hypothesized that eosinophils may react to endogenous danger signals. We found that human eosinophils migrate toward soluble uric acid and MSU crystals in a gradient-dependent manner. Eosinophils incubated with MSU crystals, but not those incubated with uric acid solution, produced elevated levels of IL-6 and IL-8/CXCL8. Other cytokines and chemokines, including IL-1beta, IL-10, IL-17, IFN-gamma, CCL2, CCL3, CCL4, TNF-alpha, G-CSF, GM-CSF, fibroblast growth factor, vascular endothelial growth factor, and TGF-beta, were also produced by eosinophils incubated with MSU crystals. Eosinophils exposed to MSU crystals rapidly (i.e., within 1 min of exposure) released ATP into the extracellular milieu. Importantly, this autocrine ATP was necessary for eosinophils to produce cytokines in response to MSU crystals, and P2 nucleotide receptors, in particular P2Y(2), are likely involved in this positive feedback loop. Finally, at higher concentrations, MSU crystals promoted P2R-dependent release of a granule protein (eosinophil-derived neurotoxin) and cell death. Thus, human eosinophils may respond to particulate damage-associated endogenous danger signals. These responses by eosinophils to tissue damage may explain the self-perpetuating nature of chronic inflammation in certain human diseases, such as asthma. |
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Authors:
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Takehito Kobayashi; Hideaki Kouzaki; Hirohito Kita |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-05-05 |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 184 ISSN: 1550-6606 ISO Abbreviation: J. Immunol. Publication Date: 2010 Jun |
Date Detail:
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Created Date: 2010-05-20 Completed Date: 2010-06-14 Revised Date: 2011-07-28 |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 6350-8 Citation Subset: AIM; IM |
Affiliation:
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Division of Allergic Diseases, Department of Medicine and Department of Immunology, Mayo Clinic, Rochester, MN 55905, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adenosine Triphosphate
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metabolism* Cell Separation Chemotaxis, Leukocyte / immunology Cytokines / biosynthesis, immunology Enzyme-Linked Immunosorbent Assay Eosinophils / immunology*, metabolism Flow Cytometry Humans Receptors, Purinergic P2 / immunology, metabolism Receptors, Purinergic P2Y2 Signal Transduction / immunology* Uric Acid / immunology*, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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AI34486/AI/NIAID NIH HHS; R01 AI034486-14/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Cytokines; 0/P2RY2 protein, human; 0/Receptors, Purinergic P2; 0/Receptors, Purinergic P2Y2; 56-65-5/Adenosine Triphosphate; 69-93-2/Uric Acid |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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