Inhibition of Polymorphonuclear Leukocyte–Mediated Graft Damage Synergizes With Short-Term Costimulatory Blockade to Prevent Cardiac Allograft Rejection

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Abstract
Background— The early inflammatory response during reperfusion of cardiac allografts is initiated by the infiltration of polymorphonuclear leukocytes (PMNs) into the graft. The impact of early PMN infiltration on allograft rejection compared with long-term graft survival remains poorly understood. Methods and Results— We tested the role of CXCR2, the receptor for 2 PMN attractant chemokines, KC/CXCL1 and MIP-2/CXCL2, on intragraft inflammation and vascularized cardiac allograft rejection in a murine model. Compared with allografts retrieved from control recipients, both PMN infiltration and intragraft proinflammatory cytokine expression were significantly attenuated in allografts from CXCR2-antisera–treated wild-type or from CXCR2−/− recipients. Adoptive transfer of alloantigen-primed T cells rapidly infiltrated and rejected allografts in control recipients, but T-cell infiltration was significantly decreased in recipients depleted of PMNs at transplantation. The influence of early PMN-mediated inflammati...