Activation of donor-derived eosinophils during static storage contributes to primary graft dysfunction after lung...

Ischemia-reperfusion injury (IRI) contributes to deleterious outcomes after lung transplantation. Although we have shown a unique protective role for eosinophils in both establishing and maintaining lung allograft tolerance, their role in IRI remains unclear. Based on previous research demonstrating a protective role for eosinophils in liver IRI, we hypothesized that they might play a similar function in the lung. In this study, we show that donor-, but not recipient-derived, eosinophils worsen injury of syngeneic and allogeneic lung grafts rather than protect from it. Eosinophils in the lungs stored in a low potassium dextran-based extracellular preservation solution become activated, degranulate, and die during rewarming. This damage correlates with decreased oxygenation and increased tissue injury upon reperfusion. In vitro studies confirm that eosinophils exposed to a clinically used low-potassium dextran-based preservation solution, but not to other preservation solutions, experience oxidative stress. Supplementing such a solution with the antioxidant glutathione, which is present in solutions used to preserve other solid organs, reduces activation and injury. While IRI has been attributed solely to graft damage mediated by recipient-derived cells entering the graft upon reperfusion, our new findings uncover a previously unrecognized role for donor-derived leukocytes in this process and open unexplored avenues to improve graft function.