| Targeting iNKT cells for the treatment of sickle cell disease. | |
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MedLine Citation:
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PMID: 21429807 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Sickle cell disease (SCD) causes widely disseminated vaso-occlusive episodes. Building on evidence implicating invariant NKT (iNKT) cells in the pathogenesis of ischemia/reperfusion injury, recent studies demonstrate that blockade of iNKT cell activation in mice with SCD reduces pulmonary inflammation and injury. In patients with SCD, iNKT cells in blood are increased in absolute number and activated in comparison to healthy controls. iNKT cell activation is reduced by agonists of adenosine 2A receptors (A(2A)Rs) such as the clinically approved coronary vasodilator, regadenoson. An ongoing multi-center, dose-finding and safety trial of infused regadenoson, has been initiated and is providing preliminary data about its safety and efficacy to treat SCD. Very high accumulation of adenosine may have deleterious effects in SCD through activation of adenosine 2B receptors that are insensitive to regadenoson. Future possible therapeutic approaches for treating SCD include selective A(2B)R antagonists and antibodies that deplete iNKT cells. |
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Authors:
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Joshua J Field; David G Nathan; Joel Linden |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Review Date: 2011-03-22 |
Journal Detail:
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Title: Clinical immunology (Orlando, Fla.) Volume: 140 ISSN: 1521-7035 ISO Abbreviation: Clin. Immunol. Publication Date: 2011 Aug |
Date Detail:
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Created Date: 2011-07-25 Completed Date: 2011-10-03 Revised Date: 2013-03-06 |
Medline Journal Info:
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Nlm Unique ID: 100883537 Medline TA: Clin Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 177-83 Citation Subset: IM |
Copyright Information:
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Copyright © 2011 Elsevier Inc. All rights reserved. |
Affiliation:
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Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adenosine A2 Receptor Antagonists
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therapeutic use Anemia, Sickle Cell / drug therapy*, immunology Animals Clinical Trials as Topic Humans Lymphocyte Activation / drug effects*, immunology Mice Natural Killer T-Cells / immunology* Purines / therapeutic use* Pyrazoles / therapeutic use* |
| Grant Support | |
ID/Acronym/Agency:
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R01 HL095704-02/HL/NHLBI NIH HHS; R01HL095704/HL/NHLBI NIH HHS; RC2HL101367/HL/NHLBI NIH HHS; UL1 TR000448/TR/NCATS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Adenosine A2 Receptor Antagonists; 0/Purines; 0/Pyrazoles; 0/regadenoson |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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