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Salutary roles of CD39 in transplantation

Version 2 2024-06-03, 18:14
Version 1 2019-07-15, 13:59
journal contribution
posted on 2024-06-03, 18:14 authored by KM Dwyer, S Deaglio, S Crikis, W Gao, K Enjyoji, TB Strom, PJ Cowan, AJF d'Apice, SC Robson
Transplantation exposes vascularized grafts to several potential injuries, including ischemia-reperfusion injury and rejection. These processes are associated with, at least in part, extracellular nucleotide-triggered (type 2 purinergic receptor) inflammatory responses that if left unchecked might compromise the long-term function and survival of the graft. Modulation of type 2 purinergic receptor-mediated signaling occurs by ectoenzymes that hydrolyze nucleotides to adenosine, which in turn activate type-1 purinergic receptors, and play a critical role in limiting inflammation and thrombosis. CD39 is the prototype nucleoside triphosphate diphosphohydrolase and is highly expressed on the endothelium. Different levels of CD39 expression by the vasculature influence the fate of the transplanted organ in ischemia-reperfusion injury and transplant rejection models. Additional roles for extracellular nucleotides/adenosine have also been defined within the immune system. Moreover, CD39 is a phenotypic marker of regulatory T cells, and through the generation of adenosine, contributes to the suppressive capabilities of these cells in vitro and in vivo. Our experimental models suggest that purinergic mechanisms may provide an integration point for the vascular and immunological responses in transplantation. CD39, the dominant ectonucleotidase, receptors for nucleotide mediators and adenosine are expressed in a regulated manner on both vascular and immune cells. We predict that administration of soluble CD39 and adenosine agonists or the targeted expression of CD39 through genetically modified organs or cells may have future therapeutic application in transplant-associated and other vascular diseases. © 2007 Elsevier Inc. All rights reserved.

History

Journal

Transplantation reviews

Volume

21

Pagination

54-63

Location

Amsterdam, The Netherlands

ISSN

0955-470X

Language

eng

Publication classification

C1.1 Refereed article in a scholarly journal

Issue

1

Publisher

Elsevier

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