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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Deletion of CD39 on natural killer cells attenuates hepatic ischemia/reperfusion injury in mice
Hepatology, Volume 51, No. 5, Year 2010
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Description
Natural killer (NK) cells play crucial roles in innate immunity and express CD39 (Ectonucleoside triphosphate diphosphohydrolase 1 [E-NTPD1]), a rate-limiting ectonucleotidase in the phosphohydrolysis of extracellular nucleotides to adenosine. We have studied the effects of CD39 gene deletion on NK cells in dictating outcomes after partial hepatic ischemia/reperfusion injury (IRI). We show in mice that gene deletion of CD39 is associated with marked decreases in phosphohydrolysis of adenosine triphosphate (ATP) and adenosine diphosphate to adenosine monophosphate on NK cells, thereby modulating the type-2 purinergic (P2) receptors demonstrated on these cells. We note that CD39-null mice are protected from acute vascular injury after single-lobe warm IRI, and, relative to control wild-type mice, display significantly less elevation of aminotransferases with less pronounced histopathological changes associated with IRI. Selective adoptive transfers of immune cells into Rag2/common gamma null mice (deficient in T cells, B cells, and NK/NKT cells) suggest that it is CD39 deletion on NK cells that provides end-organ protection, which is comparable to that seen in the absence of interferon gamma. Indeed, NK effector mechanisms such as interferon gamma secretion are inhibited by P2 receptor activation in vitro. Specifically, ATPγS (a nonhydrolyzable ATP analog) inhibits secretion of interferon gamma by NK cells in response to interleukin-12 and interleukin-18, providing a mechanistic link between CD39 deletion and altered cytokine secretion. Conclusion: We propose that CD39 deficiency and changes in P2 receptor activation abrogate secretion of interferon gamma by NK cells in response to inflammatory mediators, thereby limiting tissue damage mediated by these innate immune cells during IRI. Copyright © 2009 by the American Association for the Study of Liver Diseases.
Authors & Co-Authors
Banz, Yara
United States, Boston
Harvard Medical School
Switzerland, Bern
University of Bern
Kroemer, Alexander
United States, Boston
Harvard Medical School
Li, Xianchang
United States, Boston
Harvard Medical School
Junger, Wolfgang Georg
United States, Boston
Beth Israel Deaconess Medical Center
Candinas, Daniel
Switzerland, Bern
University Hospital Bern
Robson, Simon Christopher
United States, Boston
Harvard Medical School
Statistics
Citations: 73
Authors: 6
Affiliations: 4
Identifiers
Doi:
10.1002/hep.23510
ISSN:
15273350
Research Areas
Genetics And Genomics
Violence And Injury