Linked Life Data

18752325

Source:http://linkedlifedata.com/resource/pubmed/id/18752325

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2008-9-3
pubmed:abstractText
Concanavalin A (Con A)-induced injury is an established natural killer T (NKT) cell-mediated model of inflammation that has been used in studies of immune liver disease. Extracellular nucleotides, such as adenosine triphosphate, are released by Con A-stimulated cells and bind to specific purinergic type 2 receptors to modulate immune activation responses. Levels of extracellular nucleotides are in turn closely regulated by ectonucleotidases, such as CD39/NTPDase1. Effects of extracellular nucleotides and CD39 on NKT cell activation and upon hepatic inflammation have been largely unexplored to date. Here, we show that NKT cells express both CD39 and CD73/ecto-5'-nucleotidase and can therefore generate adenosine from extracellular nucleotides, whereas natural killer cells do not express CD73. In vivo, mice null for CD39 are protected from Con A-induced liver injury and show substantively lower serum levels of interleukin-4 and interferon-gamma when compared with matched wild-type mice. Numbers of hepatic NKT cells are significantly decreased in CD39 null mice after Con A administration. Hepatic NKT cells express most P2X and P2Y receptors; exceptions include P2X3 and P2Y11. Heightened levels of apoptosis of CD39 null NKT cells in vivo and in vitro appear to be driven by unimpeded activation of the P2X7 receptor. CONCLUSION: CD39 and CD73 are novel phenotypic markers of NKT cells. In turn, CD39 expression [corrected] modulates nucleotide-mediated cytokine production by, and limits apoptosis of, hepatic NKT cells. Deletion of CD39 is protective in [corrected] Con A-induced hepatitis. This study illustrates a [corrected] role for purinergic signaling in NKT-mediated mechanisms that result in liver immune injury.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1527-3350
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
48
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
841-52
pubmed:dateRevised
2011-9-26
pubmed:meshHeading
pubmed-meshheading:18752325-5'-Nucleotidase, pubmed-meshheading:18752325-Adenosine Triphosphate, pubmed-meshheading:18752325-Animals, pubmed-meshheading:18752325-Antigens, CD, pubmed-meshheading:18752325-Apoptosis, pubmed-meshheading:18752325-Apyrase, pubmed-meshheading:18752325-Concanavalin A, pubmed-meshheading:18752325-Disease Models, Animal, pubmed-meshheading:18752325-Drug-Induced Liver Injury, pubmed-meshheading:18752325-Killer Cells, Natural, pubmed-meshheading:18752325-Mice, pubmed-meshheading:18752325-Mice, Inbred C57BL, pubmed-meshheading:18752325-Mice, Knockout, pubmed-meshheading:18752325-Mitogens, pubmed-meshheading:18752325-Nucleotides, pubmed-meshheading:18752325-Receptors, Purinergic P2, pubmed-meshheading:18752325-Receptors, Purinergic P2X7, pubmed-meshheading:18752325-T-Lymphocyte Subsets
pubmed:year
2008
pubmed:articleTitle
Natural killer T cell dysfunction in CD39-null mice protects against concanavalin A-induced hepatitis.
pubmed:affiliation
Liver and Transplantation Centers, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural