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2016 ; 16
(10
): 2781-2794
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Unlocking the Potential of Purinergic Signaling in Transplantation
#MMPMID27005321
Zeiser R
; Robson SC
; Vaikunthanathan T
; Dworak M
; Burnstock G
Am J Transplant
2016[Oct]; 16
(10
): 2781-2794
PMID27005321
show ga
Purinergic signaling has been recognized as playing an important role in
inflammation, angiogenesis, malignancy, diabetes and neural transmission.
Activation of signaling pathways downstream from purinergic receptors may also be
implicated in transplantation and related vascular injury. Following
transplantation, the proinflammatory "danger signal" adenosine triphosphate (ATP)
is released from damaged cells and promotes proliferation and activation of a
variety of immune cells. Targeting purinergic signaling pathways may promote
immunosuppression and ameliorate inflammation. Under pathophysiological
conditions, nucleotide-scavenging ectonucleotidases CD39 and CD73 hydrolyze ATP,
ultimately, to the anti-inflammatory mediator adenosine. Adenosine suppresses
proinflammatory cytokine production and is associated with improved graft
survival and decreased severity of graft-versus-host disease. Furthermore,
purinergic signaling is involved both directly and indirectly in the mechanism of
action of several existing immunosuppressive drugs, such as calcineurin
inhibitors and mammalian target of rapamycin inhibitors. Targeting of purinergic
receptor pathways, particularly in the setting of combination therapies, could
become a valuable immunosuppressive strategy in transplantation. This review
focuses on the role of the purinergic signaling pathway in transplantation and
immunosuppression and explores possible future applications in clinical practice.