CD39 and ischemia-reperfusion injury (IRI)
In CD39 and CD73 knockout mice, organ damage and inflammation caused by
ischemia in the brain [84], heart[137-139], kidney [140,
141], liver [142, 143], intestine[144, 145] and hindlimb[146] were more severe than those in the
corresponding wild-type mice. Studies have shown that boosting of CD39
can reduce organ damage caused by IR [147-150].
The protective effect observed in CD39 over-expressing mice on
myocardial ischemia has been shown to work through the
A2BR dependence mechanism [151].
This protective effect was also observed in pigs over-expressing CD39[152]. A variety of immune cells are involved in
the protective effect of CD39 on IRI. In vitro activated Tregs
ameliorated IRI through a CD39-dependent mechanism[153]. In addition, deletion of CD39 in NK cells
inhibits their activation and protects partial hepatic IRI by
diminishing IFN-γ production [67].IRI is inherent
in organ transplantation and has an impact on both short-term and
long-term outcomes of the transplantation. CD39 expression in mouse
liver conventional myeloid DCs (mDCs) limits the pro-inflammatory
activity of mDCs and provides protection against the innate immune
response against liver transplant IRI [78].
Furthermore, liver grafts from CD39-over-expressing mice have been shown
to be protected from IRI due to the reduced numbers of resident
CD4+ T-cells [154]. The
expression of CD39 can be up-regulated by hypoxia and specificity
protein 1 (Sp1)-mediated induction of cardiac CD39 during myocardial
ischemia [24].