Background: Ex vivo lung perfusion (EVLP) has emerged as a modern preservation technique, developed to evaluate candidate donor lungs in a normothermic and metabolically active state.Donor leukocytes are linked to the development of transplant related ischemia reperfusion injury, primary graft dysfunction, and acute rejection. Pharmacologic strategies to enhance donor leukocyte depletion during EVLP have not yet been described. Plerixafor (Mozobil) is a clinically available CXCR4 receptor antagonist, which disrupts the interaction between CXCR4 and SDF-1a and facilitates mobilization of hematopoietic stem cells into peripheral circulation. Thus, we tested the hypothesis that Plerixafor improves donor leukocyte depletion during ex vivo lung perfusion.

Methods: Sprague Dawley rats (Vendor: Charles River, Male) were intubated and ventilated. The lungs were flushed with 4[deg]C low-potassium dextran solution (Perfadex, XVIVO, Gothenburg, Sweden). The heart-lung blocks were removed and subjected to 3 hours of either cold storage, EVLP, or EVLP and Plerixafor. Leukocytes were stained with an anti-CD45 antibody (Biolegend). Cell counts (cells/mL) were determined using BD Trucount tubes and analyzed using a LSR II flow cytometer (BD Biosciences).

Results: Leukocytes depleted during preservation (EVLP vs. EVLP and plerixafor) were expressed as the absolute number of CD45+ cells in the perfusate over the total number of CD45+ cells. Interestingly, Mozobil administration during EVLP significantly improved donor leukocyte depletion (37.8±4.4%, n=3) compared to EVLP (13.9±2.3%, n=4).

Conclusion: This study demonstrates plerixafor improves donor leukocyte depletion during EVLP, which may represent a novel pharmacologic strategy to reduce post-transplant related ischemia reperfusion injury, primary graft dysfunction, and acute rejection.

CITATION INFORMATION: Davis R., Gao Q., Yerxa J., Daneshmand M., Haney J., Klapper J., Hartwig M., Barbas A. CXCR4 Inhibition Improves Donor Leukocyte Depletion during Ex Vivo Lung Perfusion Am J Transplant. 2017;17 (suppl 3).

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