Document Detail


Targeting iNKT cells for the treatment of sickle cell disease.
MedLine Citation:
PMID:  21429807     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Joshua J Field; David G Nathan; Joel Linden
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Review     Date:  2011-03-22
Journal Detail:
Title:  Clinical immunology (Orlando, Fla.)     Volume:  140     ISSN:  1521-7035     ISO Abbreviation:  Clin. Immunol.     Publication Date:  2011 Aug 
Date Detail:
Created Date:  2011-07-25     Completed Date:  2011-10-03     Revised Date:  2014-11-16    
Medline Journal Info:
Nlm Unique ID:  100883537     Medline TA:  Clin Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  177-83     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier Inc. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Adenosine A2 Receptor Antagonists / 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:
R01 HL095704/HL/NHLBI NIH HHS; R01 HL095704-02/HL/NHLBI NIH HHS; R01 HL111969/HL/NHLBI NIH HHS; R01HL095704/HL/NHLBI NIH HHS; RC2HL101367/HL/NHLBI NIH HHS; UL1 TR000448/TR/NCATS NIH HHS
Chemical
Reg. No./Substance:
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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